TABLE OF CONTENTS. Genoptix Medical Laboratory 2110 Rutherford Road Carlsbad, CA Phone: Fax:

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1 TESTING DIRECTORY

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3 TABLE OF CONTENTS Genoptix Medical Laboratory 2110 Rutherford Road Carlsbad, CA Phone: Fax: Client Services Phone: Fax: CLIA No: 05D CA Clinical Lab License No: CLF CAP LAP No: Patient Privacy, Confidentiality, and HIPAA Information 1 CPT Codes 1 COMPASS Bone Marrow Evaluation 2 COMPASS Blood Evaluation 3 CHART 4 NexCourse 5 Second Opinion Consultation 6 Bone Marrow Morphology 7 Blood Morphology 7 Intelligent Flow Profile (Blood or Bone Marrow) Global 8 Intelligent Flow Profile (Fresh Tissue) Global 8 Immunophenotyping Profile (Blood or Bone Marrow) Tech only 9 Immunophenotyping Profile (Fresh Tissue) Tech only 9 Intelligent Flow Profile (Blood or Bone Marrow) Interpretation only 10 CLL MRD Profile Global 10 Myeloma MRD Profile Global 11 PNH Evaluation Global 11 Acute Leukemia Panel Tech only add on 12 Mature B-cell Panel Tech only add on 12 LGL Panel Tech only add on 13 Myeloma Panel Tech only add on 13 B-cell Clonality Tech only add on 14 Chromosome Analysis 15 FISH 15 ALL FISH Profile 16 AML FISH Profile 16 CLL FISH Profile 17 CML FISH Profile 17 MYELOMA FISH Profile 18 MDS FISH Profile 18 MPN FISH Profile 19 MPN Eosinophilia FISH Profile 19 B-cell NHL FISH Profile 20 ALK Rearrangement 20 FGFR1 Amplification 21 HER 2 Amplification 21 MET Amplification 22 RET Rearrangement 22 Laboratory Director: Bashar Dabbas, M.D. genoptix.com

4 Genoptix Medical Laboratory 2110 Rutherford Road Carlsbad, CA Phone: Fax: Client Services Phone: Fax: ROS1 Rearrangement 23 ABL1 Kinase Domain Mutation 24 AML Molecular Profile 24 B-cell Clonality Assessment 25 BRAF Mutation Analysis 25 CALR Mutation Analysis 26 CEPBA Mutation Analysis 26 ckit (D816V) Mutation Analysis 27 cobas BRAF V600 Mutation 27 EGFR Mutation Analysis 28 FLT3 Mutation Analysis 28 FLT3/NPM1 Mutation Analysis 29 GenoTRACE Quantitative BCR-ABL 29 IgVH Hypermutation Analysis 30 JAK2 Exon 12/13 30 JAK2 V617F Mutation Analysis 31 KRAS Mutation Analysis 31 Lung Molecular Profile 32 Lymphoid Molecular Profile 32 MDS Molecular Profile 33 Melanoma Molecular Profile 33 MLL-PTD Mutation Analysis 34 MPL Mutation Analysis 34 MPN Molecular Profile 35 MSI Analysis 35 Myeloid Molecular Profile 36 NexCourse Complete 36 NexCourse Solid 37 NPM1 Mutation Analysis 38 PML/RARA Quantitative Analysis 38 Prosigna Breast Cancer Prognostic Gene Signature Assay 39 T-cell Clonality Assessment 39 IHC4 (ER, PR, Ki-67, HER2 with recurrence risk score) 40 Estrogen Receptor (ER) 41 Progesterone Receptor (PR) 42 Ki HER2 43 CLIA No: 05D CA Clinical Lab License No: CLF CAP LAP No: Laboratory Director: Bashar Dabbas, M.D. genoptix.com

5 TESTING DIRECTORY PATIENT PRIVACY, CONFIDENTIALITY, AND HIPAA INFORMATION Genoptix, Inc. is committed to protecting the privacy and security of protected health information (PHI) in our possession, and to complying with all state and federal requirements applicable to the handling and release of medical records and medical information. As a provider of health care services, Genoptix is considered a covered entity under the Health Insurance Portability and Accountability Act of 1996 (HIPAA). Genoptix has developed and implemented certain policies and procedures to ensure its compliance with applicable HIPAA rules and regulations, including those pertaining to Privacy, Security, and Transaction and Code Set Standards. In accordance with the HIPAA Privacy Regulation (45 CFR ), the use and disclosure of protected health information (PHI) without a specific patient authorization is permitted in order to carry out treatment, payment, or health care operations. The Health Information Technology for Economic and Clinical Health (HITECH) Act is part of the American Recovery and Reinvestment Act (ARRA) of 2009 and amended HIPAA in several respects. Genoptix complies with the additional requirements mandated by this law which includes additional notification requirements for breaches of unsecured protected health information (PHI). Should you have questions regarding Genoptix privacy or confidentiality provisions, please contact us at The CPT codes included in this publication are in accordance with Current Procedural Terminology, a publication of the American Medical Association. CPT codes are provided here for the convenience of our clients only. Multiple units of service may be billed for CPT codes, and all CPT codes are subject to change. These codes reflect our interpretation of the code descriptions and their application to our testing procedures. Additionally, when testing is performed in combination with other assays, CPT code frequencies may decrease. Because coding accuracy is the responsibility of the billing entity, we request that you reaffirm the appropriateness of these codes by referencing to the most current version of the CPT Coding Manual of the American Medical Association (AMA) at or by visiting the Centers for Medicare and Medicaid Services (CMS) web site at: 1

6 TESTING DIRECTORY COMPASS Bone Marrow Evaluation Includes COMPASS consultation report, clinical pathology evaluation, bone marrow morphology (up to 20 stains and/or IHC antibodies), flow cytometry (up to 40 antibodies), cytogenetics and/or FISH (up to 14 probes), and molecular tests as medically necessary. Cytochemistry & immunohistochemistry, flow cytometry, chromosome analysis, FISH, and molecular testing as medically necessary. Bone marrow aspirate: 2-3 ml in green top (sodium heparin) tube. Two (2) bedside smears. Bone marrow core: Fix >1.0 cm (length) of core and/or clot in B-plus vials. Peripheral blood: 2-3 ml in purple top (EDTA) tube. 10 days Refer to individual test for CPT code(s). 2 GENOPTIX TESTING DIRECTORY

7 TESTING DIRECTORY COMPASS Blood Evaluation Includes COMPASS consultation report, clinical pathology evaluation, blood morphology (up to 10 cytochemical stains), flow cytometry (up to 40 antibodies), cytogenetics and/or FISH (up to 14 probes), and molecular tests as medically necessary. Cytochemistry, flow cytometry, chromosome analysis, FISH, and molecular testing as medically necessary. Peripheral Blood: 4-5 ml in two (2) green top (sodium heparin) tubes. And, 2-3 ml in purple top (EDTA) tube, if possible. 10 days Refer to individual test for CPT code(s). 3

8 TESTING DIRECTORY CHART When serial or subsequent COMPASS evaluations are requested on the same patient and deemed clinically appropriate by a Genoptix Hematopathologist, Genoptix will automatically provide a CHART report, unless otherwise indicated by the ordering physician. CHART includes all medically necessary technologies, and a consultative review and correlation with relevant prior findings by a Genoptix Hematopathologist. Cytochemistry & immunohistochemistry, flow cytometry, chromosome analysis, FISH, and molecular testing as medically necessary. Bone marrow aspirate: 2-3 ml in green top (sodium heparin) tube. Two (2) bedside smears. Bone marrow core: Fix >1.0 cm (length) of core and/or clot in B-plus vials. Peripheral blood: 2-3 ml in purple top (EDTA) tube. 10 days Refer to individual test for CPT code(s). 4 GENOPTIX TESTING DIRECTORY

9 TESTING DIRECTORY NexCourse If one or more solid tumor tests are ordered in a disease state, a NexCourse summary report will be issued. FISH and/or molecular testing. Preferred: Formalin-fixed paraffin embedded (FFPE) block containing non-necrotic tumor tissue, plus one (1) H&E slide cut at 4-5 microns. Alternative: Refer to individual test 7 10 days Refer to individual test for CPT code(s). 5

10 TESTING DIRECTORY CONSULTATIVE SERVICES Second Opinion Consultation Consultation by a Genoptix Hematopathologist on previously diagnosed cases. We require appropriate clinical data and slides, as well as the most recent morphology report and laboratory test results. Case dependent. Monday through Saturday/7-10 days Incomplete information on a test requisition may cause a delay in reporting , 88323, 88325, and/or x number of newly cut special stains evaluated and reported per unique biopsy specimen, x 1 Initial immunohistochemical single stain per uniquely identified biopsy specimen, (xn) number of immunohistochemical stains evaluated after initial stain 6 GENOPTIX TESTING DIRECTORY

11 TESTING DIRECTORY MORPHOLOGY Bone Marrow Morphology Preparation of blood smears and/or bone marrow core/clot for staining, morphological identification and enumeration of hematopoietic cells. H&E, cytochemical and immunohistochemistry Bone Marrow Aspirate: Four (4) to eight (8) bedside smears or 1 ml in purple-top (EDTA) tube. Bone Marrow Core: Fix >1.0 cm (length) in B-Plus vial. Place B-Plus vial in separate bag. Bone Marrow Clot: Fix >1.0 cm (length) in B-Plus vial. Place B-Plus vial in separate bag. Tech only: 2 days With interpretation: 3 days (x1) if bone marrow aspirate is evaluated and reported (xn) number of uniquely identified bone marrow biopsy specimens evaluated and reported (e.g., core and clot sections) (xn) number of uniquely identified bone marrow biopsies decalcified (xn) number of special stains, microorganisms, evaluated and reported (xn) number of special stains evaluated and reported per uniquely identified biopsy specimen (xn) number of immunohistochemical stains evaluated after initial stain (x1) Initial immunohistochemical single stain per uniquely identified biopsy specimen (e.g., core and clot sections) Blood Morphology Preparation of blood smears for staining, identification and enumeration of the morphology of blood cells. Cytochemical stains Slides: Two (2) bedside smears or 1 ml of peripheral blood in purple top (EDTA) tube. Tech only: 2 days With interpretation: 3 days x 1 if peripheral blood smear is evaluated and reported 7

12 TESTING DIRECTORY FLOW CYTOMETRY Intelligent Flow Profile (Blood or Bone Marrow) Global A 24-marker profile, with additional rational marker selection for phenotyping (up to 40 total antibodies). An evaluation of specimen adequacy and cellular integrity will also be performed. Markers include CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD11b, CD13, CD14, CD16, CD19, CD20, CD23, CD33, CD34, CD38, CD45, CD56, CD64, CD117, Kappa, Lambda, HLA-DR. Flow Cytometry Peripheral Blood: 5-6 ml in sodium heparin (green top), EDTA is acceptable Bone marrow aspirate: 2-3 ml in sodium heparin (green top) Bone marrow core: 1-2 cm minimum core length in RPMI Fluids: Equal parts RPMI and specimen Transport to lab ASAP hours 88184, x 23, Intelligent Flow Profile (Fresh Tissue) Global An 18-marker profile, with additional rational marker selection for phenotyping (up to 40 total antibodies). An evaluation of specimen adequacy and cellular integrity will also be performed. Markers include CD2, CD3, CD4, CD5, CD7, CD8, CD10,CD19, CD20, CD23, CD13, CD34, CD38, CD45, CD56, Kappa, Lambda. Flow Cytometry Fresh, unfixed tissue: 0.2 cm minimum in RPMI FNA: Equal parts RPMI and specimen Transport to lab ASAP hours 88184, (x17), GENOPTIX TESTING DIRECTORY

13 TESTING DIRECTORY FLOW CYTOMETRY Immunophenotyping Profile (Blood or Bone Marrow) Tech only An immunophenotypic 24-marker profile, including CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD11b, CD13, CD14, CD16, CD19, CD20, CD23, CD33, CD34, CD38, CD45, CD56, CD64, CD117, Kappa, Lambda, HLA-DR. Flow Cytometry Peripheral Blood: 5-6 ml in sodium heparin (green top), EDTA is acceptable Bone marrow aspirate: 2-3 ml in sodium heparin (green top) Bone marrow core: 1-2 cm minimum core length in RPMI Fluids: Equal parts RPMI and specimen Transport to lab ASAP hours 88184, (x23) Immunophenotyping Profile (Fresh Tissue) Tech only An immunophenotypic 18-marker profile, including CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD19, CD20, CD23, CD13, CD34, CD38, CD45, CD56, Kappa, Lambda. Flow Cytometry Fresh, unfixed tissue: 0.2 cm minimum in RPMI FNA: Equal parts RPMI and specimen Transport to lab ASAP hours 88184, (x17) 9

14 TESTING DIRECTORY FLOW CYTOMETRY Intelligent Flow Profile (Blood or Bone Marrow) Interpretation only Flow immunophenotyping performed at client site and submitted to Genoptix for interpretation. Additional add-on markers may be added for further classification. Flow Cytometry Analyzed data transmitted to Genoptix with aliquot of residual sample. Transport to lab ASAP hours CLL MRD Profile Global Available as a global test only. Markers include CD3, CD5, CD19, CD20, CD22, CD43, CD79b, CD81. Flow Cytometry Peripheral Blood: 5-6 ml in sodium heparin (green top) EDTA is also acceptable. Bone marrow: 2-3 ml in sodium heparin (green top) Transport to lab ASAP hours 88184, (x7), GENOPTIX TESTING DIRECTORY

15 TESTING DIRECTORY FLOW CYTOMETRY Myeloma MRD Profile Global Available as a global test only. Markers include CD19, CD20, CD27, CD38, CD45, CD56, CD117, CD138, ckappa, clambda. Flow Cytometry Peripheral Blood: 5-6 ml in sodium heparin (green top) Bone marrow: 2-3 ml in sodium heparin (green top) Transport to lab ASAP hours 88184, (x9), PNH Evaluation Global Available as a global test only. Assessment uses CD14, CD33, CD45, CD55, CD59, FLAER for determination of PNH. Flow Cytometry Peripheral Blood: 5-6 ml in sodium heparin (green top) Transport to lab ASAP hours 88184, (x5),

16 TESTING DIRECTORY FLOW CYTOMETRY Acute Leukemia Panel Tech only add on Available as a tech-only add-on after initial 24-marker immunophenotypic profile is complete. Assessment uses MPO, CD79a, CD3, CD34, TDT, CD45, CD22, CD41, CD71a, CD235a, CD61 for further evaluation/ determination of ambiguous acute leukemia. Flow Cytometry Peripheral Blood: 5-6 ml in sodium heparin (green top) Bone marrow: 2-3 ml in sodium heparin (green top) Transport to lab ASAP hours Additional (x8) when added to immunophenotyping profile Mature B-cell Panel Tech only add on Available as a tech-only add-on after initial 24-marker immunophenotypic profile is complete. Assessment uses CD103, CD25, CD19, CD20, CD11c, CD45, FMC7, CD22, CD5 for determination of B-cell disorders. Flow Cytometry Peripheral Blood: 5-6 ml in sodium heparin (green top) EDTA also acceptable Bone marrow: 2-3 ml in sodium heparin (green top) Fresh, unfixed tissue: 0.2 cm minimum in RPMI FNA: Equal parts RPMI and specimen Transport to lab ASAP hours Additional (x9) when added to immunophenotyping profile 12 GENOPTIX TESTING DIRECTORY

17 TESTING DIRECTORY FLOW CYTOMETRY LGL Panel Tech only add on Available as a tech-only add-on after initial 24-marker immunophenotypic profile is complete. Assessment uses CD57, CD56, CD4, CD8, CD3, CD45, Ta/b, Tg/d, CD16, CD5 for determination of lymphomas to define/ evaluate large granular lymphocytes (LGL) and T-cell disorders. Flow Cytometry Peripheral Blood: 5-6 ml in sodium heparin (green top) EDTA also acceptable Bone marrow: 2-3 ml in sodium heparin (green top) Transport to lab ASAP hours Additional (x10) when added to immunophenotyping profile Myeloma Panel Tech only add on Available as a tech-only add-on after initial 24-marker immunophenotypic profile is complete. Assessment uses CD81, CD27, CD28, CD56, CD138, CD19, CD38, CD45, ckappa, clambda, CD117, CD200 for determination of plasma cell disorders. Flow Cytometry Peripheral Blood: 5-6mL in sodium heparin (green top) EDTA also acceptable Bone marrow: 2-3mL in sodium heparin (green top) Transport to lab ASAP hours Additional (x12) when added to immunophenotyping profile 13

18 TESTING DIRECTORY FLOW CYTOMETRY B-cell Clonality Tech only add on Available as a tech-only add-on after initial 24-marker immunophenotypic profile is complete. Assessment uses ckappa, clambda, CD5, CD19, CD10, CD11c, CD19, CD20 for evaluation of the presence of monoclonal B-cell population with equivocal, nonspecific or absent expression of surface light chains. Flow Cytometry Peripheral Blood: 5-6 ml in sodium heparin (green top) EDTA also acceptable Bone marrow: 2-3 ml in sodium heparin (green top) Fresh, unfixed tissue: 0.2 cm minimum in RPMI FNA: Equal parts RPMI and specimen Transport to lab ASAP hours Additional (x8) when added to immunophenotyping profile 14 GENOPTIX TESTING DIRECTORY

19 TESTING DIRECTORY CYTOGENETICS Chromosome Analysis Detection of chromosomal gains and/or losses, as well as deletions, inversions, or translocations specific to hematopoietic disorders and malignancies. Cytogenetics Peripheral Blood: 5-6 ml in sodium heparin (green top) Bone Marrow: 2-3 ml in sodium heparin (green top) 7 days 88264, 88280, FISH Fluorophore-labeled probes for DNA specific targeting of aberrant chromosomes in leukemia, lymphoma, myeloproliferative/myelodysplastic disorders, and solid tumors. Flourescence in-situ hybridization (FISH) Peripheral Blood: 5-6 ml in sodium heparin (green top) Bone Marrow: 2-3 ml in sodium heparin (green top) 3-5 days manual or automated 15

20 TESTING DIRECTORY CYTOGENETICS ALL FISH Profile Assessment uses BCR-ABL t(9;22), MLL (11q23), ETV6-RUNX1 t(12;21), IGH (14q32), TCRα/δ (14q11) for determination of acute lymphoblastic leukemia. Flourescence in-situ hybridization (FISH) Peripheral Blood: 5-6 ml in sodium heparin (green top) Bone Marrow: 2-3 ml in sodium heparin (green top) Tech-only: 3 days With interpretation: 5 days (x5) automated or (x5) manual AML FISH Profile Assessment uses RUNX1T1/RUNX1 t(8;21), PML-RARA t(15;17), RARA (17q21), CBFβ inv(16), MLL (11q23) for determination of acute myeloid leukemia. Flourescence in-situ hybridization (FISH) Peripheral Blood: 5-6 ml in sodium heparin (green top) Bone Marrow: 2-3 ml in sodium heparin (green top) Tech-only: 3 days With interpretation: 5 days (x5) automated or (x5) manual 16 GENOPTIX TESTING DIRECTORY

21 TESTING DIRECTORY CYTOGENETICS CLL FISH Profile Assessment uses ATM (11q22), +12 (12cen), 13q-/-13, TP53 (17p13) for determination of chronic lymphocytic leukemia. Flourescence in-situ hybridization (FISH) Peripheral Blood: 5-6 ml in sodium heparin (green top) Bone Marrow: 2-3 ml in sodium heparin (green top) Tech-only: 3 days With interpretation: 5 days 88374, 88367, (x2) automated or 88377, 88368, (x2) manual CML FISH Profile Assessment uses BCR-ABL/ASS1 t(9;22), +8 (8cen), RARA (17q21) for determination of chronic myeloid leukemia. Flourescence in-situ hybridization (FISH) Peripheral Blood: 5-6 ml in sodium heparin (green top) Bone Marrow: 2-3 ml in sodium heparin (green top) Tech-only: 3 days With interpretation: 5 days (x2), automated or (x2), manual 17

22 TESTING DIRECTORY CYTOGENETICS MYELOMA FISH Profile Assessment uses CKS1B/CDKN2C (1p/1q), 5q-/-5/+5, 13q-/-13, TP53 (17p13), IGH/FGFR3 t(4;14), IGH/CCND1 t(11;14), IGH-MAF t(14;16) for determination of plasma cell disorders. Flourescence in-situ hybridization (FISH) Peripheral Blood: 5-6 ml in sodium heparin (green top) Bone Marrow: 2-3 ml in sodium heparin (green top) Tech-only: 3 days With interpretation: 5 days (x6), automated or (x6), manual MDS FISH Profile Assessment uses 5q-/-5/+5, 7q-/-7, +8 (8cen), 20q for determination of myelodysplasic syndrome. Flourescence in-situ hybridization (FISH) Peripheral Blood: 5-6 ml in sodium heparin (green top) Bone Marrow: 2-3 ml in sodium heparin (green top) Tech-only: 3 days With interpretation: 5 days (x2), 88367, automated or (x2), 88368, manual 18 GENOPTIX TESTING DIRECTORY

23 TESTING DIRECTORY CYTOGENETICS MPN FISH Profile Assessment uses BCR-ABL/ASS1 t(9;22), 5q-/-5/+5, 7q-/-7, +8 (8cen), 20q- for determination of myeloproliferative neoplasms. Flourescence in-situ hybridization (FISH) Peripheral Blood: 5-6 ml in sodium heparin (green top) Bone Marrow: 2-3 ml in sodium heparin (green top) Tech-only: 3 days With interpretation: 5 days (x3), 88367, automated or (x3), 88368, manual MPN Eosinophilia FISH Profile Assessment uses PDBGRα (4q12), PDGFRβ (5q32), FGFR1 (8p11) for determination of eosinophilia. Flourescence in-situ hybridization (FISH) Peripheral Blood: 5-6 ml in sodium heparin (green top) Bone Marrow: 2-3 ml in sodium heparin (green top) Tech-only: 3 days With interpretation: 5 days (x3) automated or (x3) manual 19

24 TESTING DIRECTORY CYTOGENETICS B-cell NHL FISH Profile Assessment uses IGH/CCND1 t(11;14), IGH/BCL2 t(14;18), MYC (8q24), BCL6 (3q27), MALT1 (18q21), 6q21/6q23 for determination of lymphoma subtypes. Flourescence in-situ hybridization (FISH) Peripheral Blood: 5-6 ml in sodium heparin (green top) Bone Marrow: 2-3 ml in sodium heparin (green top) Tech-only: 3 days With interpretation: 5 days (x6) automated or (x6) manual ALK Rearrangement The FDA approved Vysis ALK Break Apart FISH Probe Kit is a qualitative test that detects rearrangements involving the ALK gene via fluorescence in situ hybridization (FISH) in formalin-fixed paraffin-embedded (FFPE) non-small cell lung cancer (NSCLC) tissue specimens. Flourescence in-situ hybridization (FISH) Preferred: Two (2) FFPE blocks containing tumor tissue from the most recent surgery or biopsy. Alternative: Two (2) to Three (3) unstained FFPE tissue sections recently cut at 4 μm thickness on glass slides per marker, plus accompanying H&E stained slide. Tech-only: 3 days With interpretation: 7 days manual or automated 20 GENOPTIX TESTING DIRECTORY

25 TESTING DIRECTORY CYTOGENETICS FGFR1 Amplification Fibroblast growth factor receptor type 1 gene (FGFR1) amplification by fluorescent in situ hybridization (FISH). FGFR1 overexpression has been identified as a driver event in breast carcinoma and non-small cell lung cancer (NSCLC), particularly squamous cell carcinoma. Flourescence in-situ hybridization (FISH) Preferred: Two (2) FFPE blocks containing tumor tissue from the most recent surgery or biopsy. Alternative: Two (2) to Three (3) unstained FFPE tissue sections recently cut at 4 μm thickness on glass slides per marker, plus accompanying H&E stained slide. 7 days manual or automated HER2 Amplification Assessment of HER2 gene amplification by FISH in human breast and gastric cancer tissue specimens. Up to 20% of breast cancers overexpress the HER2 receptor. Flourescence in-situ hybridization (FISH) Preferred: Two (2) FFPE blocks containing tumor tissue from the most recent surgery or biopsy. Alternative: Two (2) to Three (3) unstained FFPE tissue sections recently cut at 4 μm thickness on glass slides per marker, plus accompanying H&E stained slide. Tech-only: 3 days With interpretation: 5 days manual or automated 21

26 TESTING DIRECTORY CYTOGENETICS MET Amplification Assessment of MET gene amplification by FISH. Alterations of the MET proto-oncogene lead to tumorigenesis and have been described in various solid tumors including lung, gastric, head and neck and brain cancers. Flourescence in-situ hybridization (FISH) Preferred: Two (2) FFPE blocks containing tumor tissue from the most recent surgery or biopsy. Alternative: Two (2) to Three (3) unstained FFPE tissue sections recently cut at 4 μm thickness on glass slides per marker, plus accompanying H&E stained slide. Tech-only: 3 days With interpretation: 7 days manual or automated RET Rearrangement RET gene rearrangement is present in up to 1~2% of non-small cell lung cancer (NSCLC), defining a molecular subset of tumors that are mutually exclusive from those caused by EGFR or KRAS mutations, and ALK or ROS1 rearrangements. Flourescence in-situ hybridization (FISH) Preferred: Two (2) FFPE blocks containing tumor tissue from the most recent surgery or biopsy. Alternative: Two (2) to Three (3) unstained FFPE tissue sections recently cut at 4 μm thickness on glass slides per marker, plus accompanying H&E stained slide. 7 days manual or automated 22 GENOPTIX TESTING DIRECTORY

27 TESTING DIRECTORY CYTOGENETICS ROS1 Rearrangement ROS1 rearrangement is present in up to 2% of non-small cell lung cancer (NSCLC), defining a molecular subset with distinct clinical characteristics that are similar to those observed in patients with ALK rearranged NSCLC. Flourescence in-situ hybridization (FISH) Preferred: Two (2) FFPE blocks containing tumor tissue from the most recent surgery or biopsy. Alternative: Two (2) to Three (3) unstained FFPE tissue sections recently cut at 4 μm thickness on glass slides per marker, plus accompanying H&E stained slide. Tech-only: 3 days With interpretation: 7 days manual or automated 23

28 TESTING DIRECTORY MOLECULAR ABL1 Kinase Domain Mutation Detection of mutations in the ABL1 kinase domain for patients with BCR-ABL1 positive CML or ALL. RNA is isolated, reverse transcribed to complementary DNA (cdna), and the DNA sequence of targeted regions of ABL (exons 4, 6-7) is determined using next generation sequencing technology. Next-Generation Sequencing (NGS) Peripheral Blood: 2-3 ml in EDTA (purple top) Bone Marrow: 2-3 ml in EDTA (purple top) days AML Molecular Profile Detection of mutations in key genes recurrently mutated in acute myeloid leukemia. Genomic DNA is isolated from bone marrow aspirates or peripheral blood and the DNA sequence of targeted regions of the ASXL1, BCOR, CEBPA, DNMT3A, EZH2, IDH1, IDH2, KIT, KRAS, NPM1, NRAS, PHF6, RUNX1, SF3B1, SRSF2, STAG2, TET2, TP53, U2AF1, WT1, and ZRSR2 genes is determined using next-generation sequencing technology. Next-Generation Sequencing (NGS) Peripheral Blood: 2-3 ml in EDTA (purple top) Bone Marrow: 2-3 ml in EDTA (purple top) 12 days GENOPTIX TESTING DIRECTORY

29 TESTING DIRECTORY MOLECULAR B-cell Clonality Assessment The detection of clonal B-cell immunoglobulin heavy chain (IGH) gene rearrangement by PCR of variable and joining regions on chromosome 14. Polymerase Chain Reaction (PCR) Peripheral Blood: 2-3 ml in EDTA (purple top) Bone Marrow: 2-3 ml in EDTA (purple top) 7 days BRAF Mutation Analysis BRAF V600E mutations are present in approximately 12% of colorectal adenocarcinomas. BRAF mutation analysis includes sectioning of FFPE tumor tissue followed by H&E staining of the tumor-rich region. DNA is extracted from a microdissected tumor section and the presence of the V600E mutation is identified by PCR. Polymerase Chain Reaction (PCR) Preferred: Two (2) formalin fixed paraffin embedded (FFPE) blocks containing tumor tissue from most recent surgery or biopsy. Alternative: Six (6) to eight (8) unstained slides at 10 μm thickness. 7 days

30 TESTING DIRECTORY MOLECULAR CALR Mutation Analysis Genomic DNA is isolated from bone marrow aspirates or peripheral blood and the DNA sequence of targeted regions of the CALR gene is determined using next generation sequencing technology. Next-Generation Sequencing (NGS) Peripheral Blood: 2-3 ml in EDTA (purple top) Bone Marrow: 2-3 ml in EDTA (purple top) 9 days CEBPA Mutation Analysis The CCAAT/enhancer binding protein alpha (CEBPA) is a key transcription factor involved in granulocyte maturation. A mutation in CEBPA is expected to interfere with DNA binding and/or dimerization. Polymerase Chain Reaction (PCR) Peripheral Blood: 2-3 ml in EDTA (purple top) Bone Marrow: 2-3 ml in EDTA (purple top) 7-10 days GENOPTIX TESTING DIRECTORY

31 TESTING DIRECTORY MOLECULAR ckit (D816V) Mutation Analysis KIT mutations are present in the majority of cases of mast cell disease/systemic mastocytosis. Patient DNA is isolated and subjected to allele-specific PCR amplification. Polymerase Chain Reaction (PCR) Peripheral Blood: 2-3 ml in EDTA (purple top) Bone Marrow: 2-3 ml in EDTA (purple top) 7-10 days cobas BRAF V600 Mutation The cobas 4800 BRAF V600 Mutation Test is an in vitro diagnostic device intended for the qualitative detection of the BRAF V600E mutation in DNA extracted from formalin fixed, paraffin-embedded human melanoma tissue. The cobas 4800 BRAF V600 Mutation Test is a real-time PCR test on the cobas 4800 system, and is intended to be used as an aid in selecting melanoma patients whose tumors carry the BRAF V600E mutation for treatment with vemurafenib. The cobas 4800 BRAF V600 Mutation Test does not reliably detect non-v600e mutations. Polymerase Chain Reaction (PCR) Preferred: Two (2) FFPE blocks: One containing tumor tissue from the most recent surgery or biopsy and another normal tissue. Alternative: One (1) to two (2) unstained formalin fixed paraffin embedded (FFPE) tissue sections cut at 5 μm thickness on glass slides, plus accompanying H&E. 7 days

32 TESTING DIRECTORY MOLECULAR EGFR Mutation Analysis DNA is extracted from microdissected tumor cells and the presence of any of 21 possible EGFR mutations in exons (including the T790M mutation in exon 20) is identified by real-time polymerase chain reaction. The test is intended to be used to select patients with NSCLC for whom tyrosine kinase inhibitor (TKI) may be indicated. Polymerase Chain Reaction (PCR) Preferred: Two (2) formalin fixed paraffin embedded (FFPE) blocks containing tumor tissue from the most recent surgery biopsy. Alternative: Two (2) unstained slides at 5 μm thickness, plus accompanying H&E. 7 days FLT3 Mutation Analysis FLT3 ITD and TKD regions are analyzed by PCR. Internal tandem duplication (ITD) is the most frequent mutation in the FLT3 gene and is associated with a poor prognosis in AML. Polymerase chain reaction (PCR) amplification for the detection of the FLT3 ITD and FLT3 TKD mutations is performed on DNA isolated from the patient sample. Polymerase Chain Reaction (PCR) Peripheral Blood: 2-3 ml in EDTA (purple top) Bone Marrow: 2-3 ml in EDTA (purple top) 7-10 days 81245, GENOPTIX TESTING DIRECTORY

33 TESTING DIRECTORY MOLECULAR FLT3/NPM1 Mutation Analysis FLT3 ITD and TKD regions are analyzed in addition to NPM1 exon 12. Internal tandem duplication (ITD) is the most frequent mutation in the FLT3 gene. Polymerase chain reaction (PCR) amplification for the detection of the FLT3 ITD, FLT3 TKD, and NPM1 mutations is performed on DNA isolated from the patient sample. Polymerase Chain Reaction (PCR) Peripheral Blood: 2-3 ml in EDTA (purple top) Bone Marrow: 2-3 ml in EDTA (purple top) 7-10 days 81245, 81246, GenoTRACE Quantitative BCR-ABL Quantitative real-time PCR is used for the detection of t(9;22) BCR-ABL1 fusion transcripts that result in p190, p210, or p230 fusion proteins. Analytical sensitivity is % on the International Scale (IS). Minimal residual disease monitoring results for the major (p210 fusions) are reported and graphed on the IS scale. Monitoring results for the minor and micro fusion breakpoints are reported. Polymerase Chain Reaction (PCR) Peripheral Blood: 2-3 ml in EDTA (purple top) Bone Marrow: 2-3 ml in EDTA (purple top) 4 days (major breakpoints), (minor breakpoints), (other breakpoints) 29

34 TESTING DIRECTORY MOLECULAR IgVH Hypermutation Analysis Somatic hypermutation of the IGH V region occurs naturally during B-cell maturation in lymphoid follicles. DNA sequencing of the amplified IGH gene variable (V) region is performed and is compared to the germline (unmutated) consensus sequence. Polymerase Chain Reaction (PCR) Peripheral Blood: 2-3 ml in EDTA (purple top) Bone Marrow: 2-3 ml in EDTA (purple top) 8 days JAK2 Exon 12/13 JAK2 encodes for a protein tyrosine kinase involved in activated signaling. Genomic DNA is isolated from bone marrow aspirates or peripheral blood and the DNA sequences of JAK2 exons are determined using next generation sequencing technology. Next-Generation Sequencing (NGS) Peripheral Blood: 2-3 ml in EDTA (purple top) Bone Marrow: 2-3 ml in EDTA (purple top) 9 days GENOPTIX TESTING DIRECTORY

35 TESTING DIRECTORY MOLECULAR JAK2 V617F Mutation Analysis JAK2 mutation results in the constitutive action of the JAK2 tyrosine kinase and is present in the majority of patients with polycythemia vera, and in a subset of other myeloproliferative neoplasms. Constitutive action of the JAK2 tyrosine kinase results in myeloproliferation in these disorders. JAK2 mutation analysis includes isolation of genomic DNA, gene amplification by quantitative PCR and probe analysis to determine the presence of the V617F (1849G>T) mutation. Polymerase Chain Reaction (PCR) Peripheral Blood: 2-3 ml in EDTA (purple top) Bone Marrow: 2-3 ml in EDTA (purple top) 4 days KRAS Mutation Analysis Detection of seven somatic mutations in the human KRAS oncogene. DNA extracted from formalin-fixed paraffin-embedded tissue is analyzed by PCR. RAS mutations are frequently associated with poor response to therapies that target the epidermal growth factor receptor (EGFR). Polymerase Chain Reaction (PCR) Preferred: Two (2) formalin fixed paraffin embedded (FFPE) blocks containing tumor tissue from most recent surgery or biopsy. Alternative: Six (6) to eight (8) unstained slides at 10 μm thickness. 7 days

36 TESTING DIRECTORY MOLECULAR Lung Molecular Profile Detection of mutations in key genes recurrently mutated in lung cancer. Genomic DNA is isolated from tissue and the DNA sequence of targeted regions of the AKT1, ALK, ARAF, BCL2L11, BRAF, DDR2, EGFR, ERBB2, FGFR1, FGFR2, FGFR3, HRAS, IGF1R, KRAS, MAP2K1, MDM2, MET, NRAS, PDGFRα, PIK3CA, PTEN, RET, ROS1, STK11, and TP53 genes is determined using next-generation sequencing technology. Next-Generation Sequencing (NGS) Preferred: Two (2) formalin fixed paraffin embedded (FFPE) blocks containing tumor tissue from the most recent surgery or biopsy or twelve (12) unstained slides at 10 µm thickness. Alternative: Eight (8) unstained slides at 10 µm thickness, plus accompanying H&E. 12 days Lymphoid Molecular Profile Detection of mutations in key genes recurrently mutated in lymphoid malignancies. Genomic DNA is isolated from bone marrow aspirates, peripheral blood, or tissue and the DNA sequence of targeted regions of the ABL1, ALK, ATM, BCL2, BCL6, BCOR, BIRC3, BRAF, BTK, CARD11, CCND1, CD79A, CD79B, CDKN2A, CREBBP, CTCF, CXCR4, DDX3X, EP300, ETV6, EZH2, FAT1, FBXW7, FOXO1, GNA13, GNAI2, HIST1H1E, ID3, IKZF1, ITPKB, JAK1, JAK2, JAK3, KMT2A/MLL, KRAS, MAPK1, MED12, MEF2B, MYC, MYD88, NF1, NOTCH1, NOTCH2, NRAS, P2RY8, PDGFRb, PIK3CD, PIM1, PLCG2, POT1, PRDM1, PTEN, PTPN11, RB1, RHOA, RIPK1, S1PR2, SAMHD1, SF3B1, SGK1, SPEN, SRC, STAT3, STAT5B, SYK, TBL1XR1, TCF3, TNFAIP3, TNFRSF14, TP53, TRAF2, TRAF3, UBR5, XPO1, ZMYM3 genes is determined using next-generation sequencing technology. Next-Generation Sequencing (NGS) Peripheral Blood: 2-3 ml in EDTA (purple top) Bone Marrow: 2-3 ml in EDTA (purple top) Tissue: Preferred: Two (2) formalin fixed paraffin embedded (FFPE) blocks containing tumor tissue from the most recent surgery or biopsy or twelve (12) unstained slides at 10 µm thickness. Alternative: Eight (8) unstained slides at 10 µm thickness, plus accompanying H&E. 12 days GENOPTIX TESTING DIRECTORY

37 TESTING DIRECTORY MOLECULAR MDS Molecular Profile Detection of mutations in key genes recurrently mutated in MDS. Genomic DNA is isolated and the DNA sequence of targeted regions of the TP53, EZH2, ETV6, RUNX1, and ASXL1 genes is determined using nextgeneration sequencing technology. Next-Generation Sequencing (NGS) Peripheral Blood: 2-3 ml in EDTA (purple top) Bone Marrow: 2-3 ml in EDTA (purple top) 10 days Melanoma Molecular Profile Detection of mutations in key genes recurrently mutated in melanoma. Genomic DNA is isolated from tissue and the DNA sequence of targeted regions of the AKT3, BRAF, CCND1, CDK4, ERBB4, GNA11, GNAQ, KIT, MAP2K1, MAP3K9, MITF, NF1, NRAS, PIK3CA and PTEN genes is determined using next generation sequencing technology. Next-Generation Sequencing (NGS) Preferred: Two (2) formalin fixed paraffin embedded (FFPE) blocks containing tumor tissue from the most recent surgery or biopsy or twelve (12) unstained slides at 10 µm thickness. Alternative: Eight (8) unstained slides at 10 µm thickness, plus accompanying H&E. 12 days

38 TESTING DIRECTORY MOLECULAR MLL-PTD Mutation Analysis A significant fraction of myelodysplastic syndromes (MDS) and MDS/acute myeloid leukemia (AML) patients have MLL partial tandem duplications (MLL-PTD). Patient RNA from peripheral blood or bone marrow is isolated and reverse transcribed to complementary DNA (cdna). Partial tandem duplications (PTD) between exons 2 and 8 in the MLL (mixed lineage leukemia) gene are amplified using multiplexed quantitative PCR. Polymerase Chain Reaction (PCR) Peripheral Blood: 2-3 ml in EDTA (purple top) Bone Marrow: 2-3 ml in EDTA (purple top) 8 days MPL Mutation Analysis MPL encodes for the thrombopoietin receptor, an important growth and survival factor for megakaryocytes. Genomic DNA is isolated from bone marrow aspirates or peripheral blood and the DNA sequence of exon 10 including W515L/K and S505 is determined using next generation sequencing technology. Next-Generation Sequencing (NGS) Peripheral Blood: 2-3 ml in EDTA (purple top) Bone Marrow: 2-3 ml in EDTA (purple top) 9 days GENOPTIX TESTING DIRECTORY

39 TESTING DIRECTORY MOLECULAR MPN Molecular Profile Detection of mutations in key genes recurrently mutated in MPNs. Genomic DNA is isolated and the DNA sequence of targeted regions of the CALR, CSF3R, JAK2, MPL and SETBP1 genes is determined using nextgeneration sequencing technology. Next-Generation Sequencing (NGS) Peripheral Blood: 2-3 ml in EDTA (purple top) Bone Marrow: 2-3 ml in EDTA (purple top) days MSI Analysis PCR and fragment analysis of paired normal and tumor tissue to determine microsatellite instability (MSI) at the standard five NCI-recommended loci. Positive results are reported as MSI-high (at least two markers are unstable) or MSI-low (one marker is unstable). Polymerase Chain Reaction (PCR) Preferred: Two (2) formalin fixed paraffin embedded (FFPE) blocks: One containing tumor tissue from the most recent surgery or biopsy and another normal tissue. Alternatively for Normal tissue PB can be used. Alternative: Seven (7) unstained slides for tumor, seven (7) unstained slides for normal at 10 μm thickness. 7 days

40 TESTING DIRECTORY MOLECULAR Myeloid Molecular Profile Detection of mutations in key genes recurrently mutated in myeloid malignancies. Genomic DNA is isolated from bone marrow aspirates or peripheral blood and the DNA sequence of targeted regions of the ASXL1, BCOR, BRAF, CALR, CEBPA, CBL, CSF3R, DNMT3A, ETV6, EZH2, GATA2, GNAS, IDH1, IDH2, JAK2, KIT, KRAS, MPL, NF1, NPM1, NRAS, PDGFRa, PDGFRb, PHF6, PTPN11, RAD21, RUNX1, SETBP1, SF3B1, SMC1A, SMC3, SRSF2, STAG2, STAT3, STAT5b, TET2, TP53, U2AF1, WT1 and ZRSR2 genes is determined using nextgeneration sequencing technology. Next-Generation Sequencing (NGS) Peripheral Blood: 2-3 ml in EDTA (purple top) Bone Marrow: 2-3 ml in EDTA (purple top) 12 days NexCourse Complete Detection of mutations in clinically relevant genomic alterations for hematological and solid tumor cancers. Genomic DNA is isolated from bone marrow aspirates, peripheral blood, or tissue and the DNA sequence of targeted regions of the ABL1, AKT1, AKT2, AKT3, ALK, APC, AR, ARAF, ASXL1, ATM, BAP1, BCL2, BCL2L11, BCL6, BCOR, BIRC3, BRAF, BRCA1, BRCA2, BTK, CALR, CARD11, CBL, CCND1, CCNE1, CD79A, CD79B, CDH1, CDK2, CDK4, CDK6, CDKN1B, CDKN2A, CEBPA, CREBBP, CRLF2, CSF1R, CSF3R, CTCF, CTNNB1, CXCR4, DDR2, DDX3X, DNMT3A, EGFR, EP300, EPHA2, ERBB2, ERBB3, ERBB4, ESR1, ETV6, EZH2, FAT1, FBXW7, FGFR1, FGFR2, FGFR3, FGFR4, FLT1 (VEGFR1), FLT3, FOXO1, GATA2, GATA3, GNA11, GNA13, GNAI2, GNAQ, GNAS, HIF1A, HIST1H1E, HNF1A, HRAS, ID3, IDH1, IDH2, IGF1R, IKZF1, IKBKB, JAK1, JAK2, JAK3, KDR, KEAP1, KIT, KMT2A/MLL, KRAS, MAP2K1, MAP2K2, MAP2K4, MAP3K1, MAP3K9, MAPK1, MCL1, MDM2, MED12, MEF2B, MET, MITF, MPL, MTOR, MYC, MYD88, NF1, NKX2-1, NOTCH1, NOTCH2, NPM1, NRAS, NTRK1, PALB2, P2RY8, PBRM1, PDGFRA, PDGFRB, PHF6, PIK3CA, PIK3CD, PIK3R1, PIM1, PLCG2, POT1, PRDM1, PTCH1, PTEN, PTPN11, RAD21, RB1, RET, RHEB, RHOA, RICTOR, RIPK1, RIT1, ROS1, RUNX1, S1PR2, SAMHD1, SETBP1, SF3B1, SGK1, SMAD4, SMARCB1, SMC1A, SMC3, SMO, SOX2, SPEN, SPOP, SRC, SRSF2, STAG2, STAT3, STAT5B, STK11, SYK, TBL1XR1, TCF3, TET2, TNFAIP3, TNFRSF14, TP53, TRAF2, TRAF3, TSC1, TSC2, U2AF1, UBR5, VHL, WT1, XPO1, ZMYM3, ZRSR2 genes is determined using next generation sequencing technology. Next-Generation Sequencing (NGS) Peripheral Blood: 2-3 ml in EDTA (purple top) Bone Marrow: 2-3 ml in EDTA (purple top) Tissue: Preferred: Two (2) formalin fixed paraffin embedded (FFPE) blocks containing tumor tissue from the most recent surgery or biopsy or twelve (12) unstained slides at 10 µm thickness. Alternative: Eight (8) unstained slides at 10 µm thickness, plus accompanying H&E. 36 GENOPTIX TESTING DIRECTORY

41 TESTING DIRECTORY MOLECULAR 12 days NexCourse Solid Detection of mutations in clinically relevant genomic alterations for solid tumor carcinoma. Genomic DNA is isolated from tissue and the DNA sequence of targeted regions of the ABL1, AKT1, AKT2, AKT3, ALK, APC, AR, ARAF, BAP1, BCL2L11, BRAF, BRCA1, BRCA2, BTK, CBL, CCND1, CCNE1, CDH1, CDK2, CDK4, CDK6, CDKN1B, CDKN2A, CSF1R, CTCF, CTNNB1, DDR2, DDX3X, EGFR, EPHA2, ERBB2, ERBB3, ERBB4, ESR1, ETV6, FBXW7, FGFR1, FGFR2, FGFR3, FGFR4, FLT1 (VEGFR1), FLT3, FOXO1, GATA3, GNA11, GNAQ, GNAS, HIF1A, HNF1A, HRAS, IDH1, IDH2, IGF1R, JAK1, JAK2, JAK3, KDR, KEAP1, KIT, KMT2A/MLL, KRAS, MAP2K1, MAP2K2, MAP2K4, MAP3K1, MAP3K9, MAPK1, MCL1, MDM2, MED12, MET, MITF, MTOR, MYC, NF1, NKX2-1, NOTCH1, NOTCH2, NRAS, NTRK1, PALB2, PBRM1, PDGFRa, PDGFRb,PIK3CA, PIK3CD, PIK3R1, PTCH1, PTEN, PTPN11, RB1, RET, RHEB, RHOA, RICTOR, RIT1, ROS1, RUNX1, SMAD4, SMARCB1, SMO, SPEN, SPOP, SRC, STK11, SYK, TP53, TSC1, TSC2, VHL genes is determined using next generation sequencing technology. Next-Generation Sequencing (NGS) Preferred: Two (2) formalin fixed paraffin embedded (FFPE) blocks containing tumor tissue from the most recent surgery or biopsy. Alternative: Twelve (12) unstained slides at 10 µm thickness, plus accompanying H&E. 12 days

42 TESTING DIRECTORY MOLECULAR NPM1 Mutation Analysis Exon 12 of NPM1 is analyzed by PCR to detect small insertion mutations specific to AML. Polymerase chain reaction (PCR) amplification for the detection of NPM1 mutations is performed on DNA isolated from the patient sample. Polymerase Chain Reaction (PCR) Peripheral Blood: 2-3 ml in EDTA (purple top) Bone Marrow: 2-3 ml in EDTA (purple top) 7-10 days PML/RARA Quantitative Analysis RT-PCR for quantitative detection of t(15;17) PML/RARA, a recurrent genetic abnormality found in a subset of patients with acute promyelocytic leukemia (APL). This test detects all three gene fusion patterns: type A (short, S-form, bcr-3), type B (long, L-form, bcr-1), and type B variant (variable, V-form, bcr-2). This quantitative assay allows PML/RARA levels to be monitored rather than simply detecting the presence or absence of disease. Polymerase Chain Reaction (PCR) Peripheral Blood: 2-3 ml in EDTA (purple top) Bone Marrow: 2-3 ml in EDTA (purple top) 7-10 days GENOPTIX TESTING DIRECTORY

43 TESTING DIRECTORY MOLECULAR Prosigna Breast Cancer Prognostic Gene Signature Assay The Prosigna Breast Cancer Prognostic Gene Signature Assay is an invitro diagnostic assay which is performed on the NanoString ncounter Dx Analysis System using FFPE breast tumor tissue previously diagnosed as invasive breast carcinoma. This qualitative assay utilizes gene expression data, weighted together with clinical variables to generate a risk category and numerical score, to assess a patient s risk of distant recurrence of disease. Preferred: Formalin-fixed, minimum 4mm paraffin-embedded (FFPE) viable invasive breast carcinoma (ductal, lobular, mixed, or NOS) with at least 10% tumor cellularity. Alternative: Six (6) unstained slides (minimum of 3), each 10 microns in thickness. 10 days T-cell Clonality Assessment Detection of clonal TCR-beta gene rearrangements by PCR of variable and joining regions on chromosome 7. Polymerase Chain Reaction (PCR) Peripheral Blood: 2-3 ml in EDTA (purple top) Bone Marrow: 2-3 ml in EDTA (purple top) 7 days

44 TESTING DIRECTORY IHC4 (ER, PR, Ki-67, HER2 with recurrence risk score) The immunohistochemical 4 (IHC4) score is a prognostic score for recurrence risk assessment that is a quantitative measurement of estrogen and progesterone expression by AQUA Technology, the Ki-67 expression percentage by AQUA Technology, and the HER2 expression status by IHC or FISH testing. Automated Quantitative Analysis (AQUA) Technology and IHC or FISH. Preferred: Formalin-fixed paraffin embedded (FFPE) tissue containing sufficient tumor cells for analysis. Large, preferably multiple core biopsies or properly fixed excisional biopsy, representative of tumor grade. Acceptable alternative: At least ten (10) unstained slides at 4 microns, plus one (1) accompanying H&E slide. 10 days Refer to individual test for CPT code(s). 40 GENOPTIX TESTING DIRECTORY

45 TESTING DIRECTORY Estrogen Receptor (ER) Estrogen receptor (ER) by AQUA Technology is reported as either negative or positive with the cutoff score = 11. A score <11 indicates negative ER expression. A score >11 indicates positive ER expression. If all markers for IHC4 are performed and ER result is negative, an IHC4 residual recurrence risk score and recurrence rate will not be reported. ER expression by IHC is measured in accordance with CAP/ASCO guidelines. Receptor expression is detected by binding of a monoclonal rabbit anti-human ER antibody (clone SP1). ER status is determined by the percentage of stained cells. Automated Quantitative Analysis (AQUA) or IHC Preferred: Formalin-fixed paraffin embedded (FFPE) block containing non-necrotic tumor tissue, plus one (1) H&E slide cut at 4-5 microns. Acceptable alternative: Four (4) positively charged unstained slides cut at 4-5 microns, plus one (1) accompanying H&E slide (required). AQUA Technology: 7-10 days IHC: 2 days AQUA Technology: 88313, (x2) IHC: tumor IHC, manual or tumor IHC, computer assisted 41

46 TESTING DIRECTORY Progesterone Receptor (PR) Progesterone receptor (PR) by AQUA Technology is reported as either negative or positive with the cutoff = 30. A score >30 indicates positive ER expression. PR expression by IHC is measured in accordance with CAP/ASCO guidelines. Receptor expression is detected by binding of a monoclonal mouse anti-pr antibody (clone 1E2). PR status is determined by the percentage of stained cells. Automated Quantitative Analysis (AQUA) or IHC Preferred: Formalin fixed paraffin embedded (FFPE) block containing non-necrotic tumor tissue, plus one (1) H&E slide cut at 4-5 microns. Acceptable alternative: Four (4) positively charged unstained slides cut at 4-5 microns, plus one (1) accompanying H&E slide (required). AQUA Technology: 7-10 days IHC: 2 days AQUA Technology: 88313, (x2) IHC: 88360, manual or 88361, computer assisted 42 GENOPTIX TESTING DIRECTORY

47 TESTING DIRECTORY Ki-67 Ki-67 is a nuclear protein expressed in proliferating cells and its expression is detected by either IHC or AQUA technology. Ki-67 by AQUA Technology is reported as a percentage of expression ranging between 0-100%. Ki-67 by IHC is detected by a monoclonal rabbit anti-human Ki-67 antibody (clone 30-9). Ki-67 expression status is determined by the percentage of stained tumor cells. Automated Quantitative Analysis (AQUA) or IHC Preferred: Formalin fixed paraffin embedded block containing non-necrotic tumor tissue, plus one (1) H&E slide cut at 4-5 microns. Acceptable alternative: Four (4) positively charged unstained slides cut at 4-5 microns, plus one (1) accompanying H&E slide (required). AQUA Technology: 7-10 days IHC: 2 days AQUA Technology: 88313, (x2) IHC: manual or computer assisted HER2 HER2 (c-erbb-2) expression by IHC is measured in accordance with CAP/ASCO Guidelines. HER2 expression level is detected by binding of a monoclonal rabbit anti-human HER2 antibody (clone 4B5). HER2 expression level is determined by the percentage of tumor cells with complete or intense staining. IHC Preferred: Formalin fixed paraffin embedded block containing non-necrotic tumor tissue, plus one (1) H&E slide cut at 4-5 microns. Acceptable alternative: Four (4) positively charged unstained slides cut at 4-5 microns, plus one (1) accompanying H&E slide (required). IHC: 2 days IHC: manual or computer-assisted 43

48 Genoptix, Inc. Genoptix, COMPASS, CHART, NexCourse and GenoTRACE are registered trademarks of Genoptix, Inc. cobas is a registered trademark of Roche Diagnostics, NanoString, Prosigna, and ncounter are registered trademarks of NanoString Technologies, AQUA is a registered trademark of HistoRx, Inc., Vysis is a registered trademark of Abbot Group April Rutherford Rd. Carlsbad, CA P F