Histolab Products AB Eva Alströmer Jonas Falgén Helsingborg 7-8/10 2010
Table 1 Formalin Fixation Times and Estrogen Receptor Staining With 25 Minutes Antigen Retrieval Pretreatment Formalin Q-Score Difference in Q-Score p-value* Fixation Time (range) (Case Maximum - Block) 3 hours 1.75 (0-5) 5.00 (2-7) < 0.001 6 hours 4.67 (2-7) 2.12 (0-5) < 0.001 8 hours 6.46 (4-7) 0.33 (0-3) 0.490 10 hours 6.62 (4-7) 0.17 (0-3) 0.153 12 hours 6.17 (3-7) 0.62 (0-4) 0.278 1 day 5.71 (3-7) 1.08 (0-4) 1.005 2 days 4.48 (2-7) 2.33 (0-5) 0.086 7 days 3.79 (2-7) 3.00 (0-5) *Compared to adjacent longer-fixed block
Table 2 Formalin Fixation Times and Estrogen Receptor Staining With Standard, 40 Minutes Antigen Retrieval Pretreatment Formalin Q-Score Difference in Q-Score p-value* Fixation Time (range) (Case Maximum - Block) 3 hours 2.46 (0-6) 4.36 (1-7) < 0.001 6 hours 5.75 (2-7) 1.14 (0-4) < 0.001 8 hours 6.70 (5-7) 0.04 (0-1) 0.791 10 hours 6.70 (5-7) 0.08 (0-1) 0.791 12 hours 6.70 (5-7) 0.04 (0-1) 1.000 1 day 6.70 (5-7) 0.04 (0-1) 1.000 2 days 6.70 (5-7) 0.04 (0-1) 0.625 7 days 6.60 (5-7) 0.12 (0-1)
Screeners Lymphoma Carcinoma AE1/AE3 LCA AEI/AE3 LCA L26 (CD20) LMW CK (CAM5.2) S100 UCHL-1 (CD45RO) HMW CK (34betaE12/CK903) MSA/Vimentin CD15 (LeuM1) CEA (colon cancer) CD43 (Leu 7) EMA CD68 PSA PSAP Melanoma S100 HMB45 Sarcoma Muscle Specific Actin Vimentin Smooth Muscle Actin Synpatophysin (R) Chromogranin GFAP Factor VIII
Idag finns det fler är 300 antikroppsföretag, 30 000+ antikroppar och runt 150-400 antikroppar som används kliniskt!
New Clinical Antibodies Prognostic/Predictive Panel Multiplex Antibodies Glypican-3 HIF-1, alpha PIN-4 SALL4 GLUT-1 ADH-5 CD163 VEGF URO-3 Synaptophysin GATA-3 Glypican-3 + CK19 DOG1 COX-2 CD4 + CD8 Napsin A phh3 TTF-1 + Napsin A PAX8 ERG p63 + CK5 P63 (IVD) GCDFP-15 + Mammaglobin Infectious Disease Stem Cells CD10 + Cyclin 1 Cat scratch CD24 CD23 + CD5 H. pylori CD44 Kappa + Lambda Spirochete ALDH1a CDX2 + CK7 TB CD133
DOG1 DOG1 (protein kinase C theta) is a cell surface protein of unknown function selectively expressed in gastrointestinal stromal tumors (GIST). In addition to being expressed in typical GISTs, DOG1 is also highly expressed in KITmutation-negative GISTs. GIST stained with DOG1 antibody
DOG1- Significance DOG1 is a novel mouse monoclonal antibody reported to have superior sensitivity and specificity compared with KIT (CD117) and CD34. Among GIST cases with KIT mutations, DOG1 detected 11% more cases than CD117. In KIT/CD117 negative and PDGFRA-mutant GIST cases, DOG1 increased the accuracy of GIST diagnosis. DOG1 can serve as additional target in the diagnosis and likely imatinib mesylate treatment of GIST patients. DOG1 immunoreactivity is seen in fewer non-gist cases of mesenchymal, epithelial tumors, seminomas and melanomas when compared with CD117.
Glypican-3 Glypican-3 (GPC3) is a member of the glypican family of glycosyl phosphatidylinositol-anchored cell-surface heparin sulfate proteoglycans. The 1G12 clone has been used to assess GPC3 expression in malignant and non-malignant tissue samples of the liver. Studies have shown that GPC3 protein is expressed in most hepatocellular carcinomas (HCC), but is undetectable in normal liver and benign hepatic lesions, including dysplastic and cirrhotic nodules. GPC3 is also significantly elevated in the serum of most patients with HCC. Several studies report that Glypican-3 is a useful diagnostic marker for HCC and a tool for differentiating HCC from non-neoplastic and preneoplastic liver disease. Our studies have shown that Glypican-3 is positive in 90.4% of hepatocellular carcinoma cases and negative in 100% of cholangiocellular carcinoma, normal liver and hyperplasia cases. Liver cancer stained with Glypican-3 antibody
Glypican-3 Clinical Relevance Expression of GPC3 was shown in fetal liver and malignant hepatocytes in both hepatoblastomas and HCC. Studies propose that as GPC3 is much more specific and sensitive for HCC, than AFP (alpha-fetoprotein) and HepPar1 (hepatocyte antigen); it should be used in routine histological examination of liver cancer. No deaths were noted in the GPC3-negative HCC patients among the 71 (88.7%) patients with moderately and poorly differentiated HCC. Multivariate analysis identified GPC3 expression (P = 0.034) as an independent prognostic factor for the overall survival. Glypican-3 + CK19 Double stain
Glypican-3 + CK19 CK19 is of prognostic value in HCC and may be used to distinguish cholangiocellular carcinoma (CK19 +) from HCC (CK19 -); or focal nodular hyperplasia (CK19 +) from hepatic adenoma (CK19 -). Studies also show CK19 expression as an independent prognostic factor for HCC with lymph node metastasis. GPC3 + CK19 Multiplex IHC can help distinguish hepatocellular carcinomas vs. cholangiocellular carcinomas vs. metastatic tumors of the liver. Cholangiocarcinoma stained with Glypican-3 + CK19
Glypican-3 + CK19 Clinical Relevance GPC3 + CK19 allows for distinction between HCC with intrahepatic cholangiocellular carcinoma-like differentiation (CK19+) and HCC with a higher T-classification (CK19 -), impacting the recommended treatment regime. GPC3 stained a higher percentage of HCC (84%), when compared with IHC of hepatocyte specific antigen (HSA) and alphafetoprotein. Multivariate analysis identified GPC3 expression (P = 0.034) as an independent prognostic factor for overall survival. Differentiate between hepatocellular carcinoma (HCC) vs. cholangiocellular carcinoma (CC), whilst determining the prognosis of an aggressive liver tumor phenotype. * Normal Prostate
SALL4 SALL4, a newly identified zincfinger transcriptional factor, is required for the maintenance of embryonic stem cell pluripotency by modulation of Oct4. The SALL4 gene is mapped to chromosome 20q13. Seminoma stained with SALL4 antibody
SALL4 Clinical Relevance SALL4 is a promising new pan germ-cell marker and has been shown to be superior to PLAP and Oct4 antibodies. SALL4 may serve as a valuable immunohistochemistry tool for stem cell researchrelated studies. SALL4 is a novel sensitive and specific marker for seminomas and ovarian primitive germ-cell tumors. This marker is particularly useful in distinguishing yolk sac tumors from clear cell carcinomas. In one study, 100 percent of 31 yolk sac tumors (5 pediatric and 26 postpubertal) showed strong positive SALL4 staining of tumor cells, but were negative for Oct4. Over 90% of tumor cells in intratubular germ-cell neoplasias and embryonal carcinomas show strong SALL4 staining.
Napsin A Napsin A is a pepsin-like aspartic proteinase. It is expressed in type II pneumocytes and in adenocarcinomas of the lung and kidney. Antibody panels commonly used to distinguish primary lung tumors from metastatic tumors to the lung from common sites such as breast, prostate, colon, etc., have included thyroid transcription factor 1 (TTF-1), CK7 and p63. However, Napsin A has been shown to be a specific lung adenocarcinoma marker, more so than TTF-1. Napsin A is useful for distinguishing primary lung adenocarcinoma from adenocarcinoma of unknown origin and is therefore a promising marker for the differential diagnosis of primary lung adenocarcinoma. Lung adenocarcinoma stained with Napsin A antibody
Napsin A Clinical Relevance Napsin A and surfactant apoprotein-a (SP-A) expression was noted in 84.3% and 53.0% of primary sites of lung adenocarcinomas respectively. Pulmonary adenocarcinomas were Napsin A positive in 83% of cases compared with 73% of cases that were TTF-1 positive. Co-expression of TTF-1 and Napsin A is highly indicative for lung adenocarcinoma. A suggested panel for lung adenocarcinoma would include TTF1 (+), Napsin A (+) and CK7.
Lung Adeno - 2 (TTF-1 + Napsin A) Studies have shown Napsin A to be more sensitive and specific than TTF- 1 in lung adenocarcinomas and virtually negative in all squamous carcinomas. When used in a panel with p63 and CK5, this unique antibody cocktail of TTF-1 and Napsin A should prove useful for immunohistochemical analysis of poorly differentiated lung adenocarcinomas vs. squamous cell carcinomas in formalin-fixed paraffinembedded tissues.
Lung Adeno - 2 (TTF-1 + Napsin A) Clinical Relevance When combined with the Lung Squamous-2 Multiplex IHC, this multiplex aids in the critical differentiation of NSCLC squamous vs. adenocarcinoma, which is critical in therapeutic decisions such as the use of VEGF or EGFR inhibitors. When comparing Napsin A in pulmonary adenocarcinomas, Napsin A was positive in 79 (83%) of 95 cases compared with 69 (73%) of 95 cases that were TTF-1 positive. Studies have shown that Napsin A was 100% negative for squamous cell carcinomas of the lung. When comparing Napsin A and SP-A in lung adenocarcinomas, expression was noted in 84.3% and 53.0%, respectively.
Lung Squamous - 2 (p63 + CK5) It is essential that the correct diagnosis of squamous cell carcinoma (SqCC) of the lung be determined. Patients with SqCC must not be treated with Avastin therapy due to a 30% mortality rate as a result of fatal hemoptysis (hemorrhaging). The p63 + CK5 Multiplex IHC were specifically designed for differentiation of lung SqCC from adenocarcinoma of the lung. Inhouse studies have shown sensitivity greater than 80% for lung SqCC. When used in a panel with Lung Adeno-2 (TTF-1 + Napsin A), p63 + CK5 should prove useful for immunohistochemical analysis of poorly differentiated lung adenocarcinomas vs. squamous cell carcinomas in formalin-fixed paraffin-embedded tissues. Lung squamous cell carcinoma stained with p63 and CK5
Lung Squamous - 2 (p63 + CK5) Clinical Relevance When combined with the Lung Adeno-2 Multiplex IHC, this multiplex aids in the critical differentiation of NSCLC squamous vs. adenocarcinoma, which is critical in therapeutic decisions such as the use of VEGF or EGFR inhibitors. Studies have shown that the combination of p63 and CK5 was useful for differentiating adenocarcinoma from squamous cell carcinoma with 100% specificity and 82% sensitivity, 89% specificity and 79% sensitivity, respectively. Our data suggests that positive immunostaining for both p63 and CK5 in poorly differentiated metastatic carcinomas is highly predictive of a primary tumor of squamous epithelial origin.
PAX8 PAX8 is shown to be expressed in a high percentage of kidney and ovarian carcinomas. PAX8 staining is localized to the nucleus and is less prone to false negatives by nonspecific background, endogenous pigments or endogenous biotin background. PAX8 specificity was demonstrated in over 1100 cases of normal and neoplastic tissues and determined that PAX8 is a specific and sensitive marker for renal cell and ovarian carcinomas and will be a valuable addition to the histopathology laboratory. Normal kidney stained with PAX 8 antibody
PAX8 Ovarian Cancer RCC metastasize into thyroid tissue
PAX8 Clinical Relevance PAX8 is a superior marker for renal cell carcinoma compared to the Renal Cell Carcinoma Marker (RCCm), staining 90% of all RCCs; 91% of clear cell RCCs and 100% of papillary RCC cases. PAX8 proved to be a specific and a sensitive marker for renal cell carcinoma (90%) and ovarian carcinomas (79%), with serous and endometrioid ovarian carcinomas having 89% sensitivity. The addition of PAX8 to the standard ovarian cancer panel (CA125, WT-1 and CK7) will be a valuable addition; especially in diagnosis of tumors of unknown origin, increasing both specificity and sensitivity.
PAX8 Table 1 Diagnosis Total Cases Positive Negative % + % - Renal cell carcinomas 122 110 12 90% 10% Ovarian cancers 245 201 44 82% 18% Endometrial cancers 134 113 21 84% 16% Thyroid tumors 10 9 1 90% 10% Neuroendocrine tumors 15 1 14 7% 93% Cervical cancers 73 7 66 4% 96% Pancreatic cancer 23 3 18 13% 87% Bladder cancers 82 6 76 7% 93% Lung cancers 100 1 99 1% 99% Colon cancers 100 0 100 0% 100% Breast cancers 100 0 100 0% 100% Prostate cancers 35 0 35 0% 100% Liver cancers 36 0 36 0% 100% Melanoma 20 0 20 0% 100% Seminoma 18 0 18 0% 100% Stomach cancers 6 0 6 0% 100% Esophageal cancers 6 0 6 0% 100% Soft Tissue Tumors 21 2 19 5% 95% 33 FDA Normal Tissues 33 *1 32 3% 97%
ADH-5 ADH-5 simplifies interpretation and helps with diagnostic challenges such as differentiation of atypical ductal hyperplasia from hyperplasia of the usual type, identifying microinvasion and invasive ductal carcinoma, and distinguishing basal phenotypes in triple negatives, by simultaneously testing for 5 key markers of breast disease in one simple procedure. CK5+CK14+p63+CK7+CK18
Hyperplasia of the usual type
Atypical Ductal Hyperplasia; CK5/14 and p63 staining basal myoepithelium (DAB), CK7/18 staining luminal epithelium (FR). Invasive breast cancer: CK7/18 only Basal phenotype: luminal expression of CK5/14 (DAB)
ADH-5 Clinical Relevance This 5 antibody cocktail has a great utility and may be used for interpretation of breast cancer on a single slide. This Cocktail differentiates between benign usual ductal hyperplasia, atypical ductal hyperplasia, microinvasion, invasive ductal carcinoma and true basal phenotypes. The five stages outlined above are thought to represent a gradual (developmental) sequence in breast cancer.
Biocare - the IVD p63 company One of only two companies with rights to distribute IVD p63 worldwide Perpetual p63 license ensures a continual supply of IVD p63 Is unaltered by recently hatched p63 licensing agreements p63 clone BC4A4
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Tack för uppmärksamheten! Eva Alströmer Jonas Falgén