Cytokeratins and generel epithelial markers in tumour classification
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1 Cytokeratins and generel epithelial markers in tumour classification 42, liver adenocarcinoma of unknown primary Colonrectum? Pancreas/biliary tract? Stomach? Lung? Ovary/endometrium? Mogens Vyberg, NordiQC 1
2 42, liver adenocarcinoma of unknown primary CDX2 42, liver adenocarcinoma of unknown primary: colonrectum CK20 CK7 Mogens Vyberg, NordiQC 2
3 Cytokeratins in diagnostic pathology Cytokeratins (CKs) belong to the most fundamental markers of epithelial differentiation CKs comprise a large family of subtypes. Different cell types express different patterns of CK subtypes Cancers generally express CK patterns that at least in part represent the pattern of the putative cell of origin Metastases express CK patterns fairly concordant with those of the primary tumours Cytokeratins a multigene family Highly complex family of polypeptides About 54 distinct human types Class I (type A Acidic): CK9 (64 kda) CK20 (40 kda) Class II (type B Basic/neutral): CK1 (68 kda) CK8 (52.5 kda) Mogens Vyberg, NordiQC 3
4 The Moll Cytokeratin catalogue 1982 (B) (A) 11? 1992 CK: renal cell carcinoma Moll et al. Cell 1982; 31:11 Pairing of cytokeratins One CK class I and one CK class II always paired CK class I in a pair ~ 8 kda smaller than class II Modified from: Lane & Alexander Semin Cancer Biol 1990, 1:165 Mogens Vyberg, NordiQC 4
5 LMW Cytokeratin types squamous epithelia Neutral/Basic (B, class II) Acidic (A, class I) Squamous epithelia: suprabasal, keratinizing suprabasal, nonkeratinizing () () basal cells ( 1 tonsil, 2 mucosa) () 1 () 2 () 1 () 1 Transit. epith.: superficial cells intermed. / 3 basal cells Mesothelial cells () 3 () 3 () 3 () Bronchus, breast, prost., cerv.: basal/myoepithelial cells luminal cells Biliary/pancr. ducts, lung alv., endometr., renal collect. ducts 4 Stomach (foveola), intestine Hepatocytes, pancr. acini, prox. renal tubules Endocrine cells ( 5 Merkel, 6 thyr.) Smooth muscle (vasc., myom.), myofibrobl., 7 sm.ves.endothelia () 4 () 5 () 6 () 5 () 7 HMW Cytokeratin types squamous epithelia CK5: esophagus CK4: esophagus Mogens Vyberg, NordiQC 5
6 HMW Cytokeratin types squamous epithelia CK17: tonsil CK17: skin Cytokeratin types urothelium Neutral/Basic (B, class II) Acidic (A, class I) Squamous epithelia: suprabasal, keratinizing suprabasal, nonkeratinizing () () basal cells ( 1 tonsil, 2 mucosa) () 1 () 12 () 1 () 1 Transit. epith.: superficial cells intermed. / 3 basal cells Mesothelium () 3 () 3 () 3 () Bronchus, breast, prost., cerv.: basal/myoepithelial cells luminal cells Biliary/pancr. ducts, lung alv., endometr., renal collect. ducts 4 Stomach (foveola), intestine Hepatocytes, pancr. acini, prox. renal tubules Endocrine cells ( 5 Merkel, 6 thyr.) Smooth muscle (vasc., myom.), myofibrobl., 7 sm.ves.endothelia () 4 () 5 () 6 () 5 () 7 Mogens Vyberg, NordiQC 6
7 Cytokeratin types urothelium CK5 (CK13) CK20 Cytokeratin types mesothelium Neutral/Basic (B, class II) Acidic (A, class I) Squamous epithelia: suprabasal, keratinizing suprabasal, nonkeratiniz.ep () () basal cells ( 1 tonsil, 2 mucosa) () 1 () 12 () 1 () 1 Transit. epith.: superficial cells intermed. / 3 basal cells Mesothelium () 3 () 3 () 3 () Bronchus, breast, prost., cerv.: basal/myoepithelial cells luminal cells Biliary/pancr. ducts, lung alv., endometr., renal collect. ducts 4 Stomach (foveola), intestine () 4 Hepatocytes, pancr. acini, prox. renal tubules Endocrine cells ( 5 Merkel, 6 thyr.) Smooth muscle (vasc., myom.), myofibrobl., 7 sm.ves.endothelia () 5 () 6 () 5 () 7 Mogens Vyberg, NordiQC 7
8 Cytokeratin types mesothelium CK19: mesothelium CK5: mesothelium (adenocarcinoma neg.) Cytokeratin types complex epithelia Neutral/Basic (B, class II) Acidic (A, class I) Squamous epithelia: suprabasal, keratinizing suprabasal, nonkeratinizing () () basal cells ( 1 tonsil, 2 mucosa) () 1 () 12 () 1 () 1 Transit. epith.: superficial cells intermed. / 3 basal cells Mesothelium () 3 () 3 () 3 () Bronchus, breast, prost., cerv.: basal/myoepithelial cells luminal cells Biliary/pancr. ducts, lung alv., endometr., renal collect. ducts 4 Stomach (foveola), intestine Hepatocytes, pancr. acini, prox. renal tubules Endocrine cells ( 5 Merkel, 6 thyr.) Smooth muscle (vasc., myom.), myofibrobl., 7 sm.ves.endothelia () 4 () 5 () 6 () 5 () 7 Mogens Vyberg, NordiQC 8
9 Cytokeratin types complex epithelia CK5 (14,17): breast CK18 (8,7): breast Cytokeratin types simple epithelia Neutral/Basic (B, class II) Acidic (A, class I) Squamous epithelia: suprabasal, keratinizing suprabasal, nonkeratinizing () () basal cells ( 1 tonsil, 2 mucosa) () 1 () 12 () 1 () 1 Transit. epith.: superficial cells intermed. / 3 basal cells Mesothelium () 3 () 3 () 3 () Bronchus, breast, prost., cerv.: basal/myoepithelial cells luminal cells Biliary/pancr. ducts, lung alv., endometr., renal collect. ducts 4 Stomach (foveola), intestine Hepatocytes, pancr. acini, prox. renal tubules Endocrine cells ( 5 Merkel, 6 thyr.) Smooth muscle (vasc., myom.), myofibrobl., 7 sm.ves.endothelia () 4 () 5 () 6 () 5 () 7 Mogens Vyberg, NordiQC 9
10 Cytokeratin types simple epithelia (liver, kidney) CK7(19): bile ducts CK7(19): renal col. Cytokeratin types simple epithelia Neutral/Basic (B, class II) Acidic (A, class I) Squamous epithelia: suprabasal, keratinizing suprabasal, nonkeratinizing () () basal cells ( 1 tonsil, 2 mucosa) () 1 () 12 () 1 () 1 Transit. epith.: superficial cells intermed. / 3 basal cells Mesothelium () 3 () 3 () 3 () Bronchus, breast, prost., cerv.: basal/myoepithelial cells luminal cells Biliary/pancr. ducts, lung alv., endometr., renal collect. ducts 4 Stomach (foveola), intestine Hepatocytes, pancr. acini, prox. renal tubules Endocrine cells ( 5 Merkel, 6 thyr.) Smooth muscle (vasc., myom.), myofibrobl., 7 sm.ves.endothelia () 4 () 5 () 6 () 5 () 7 Mogens Vyberg, NordiQC 10
11 Cytokeratin types simple epithelia CK20: gastric foveolae CK20: colon Cytokeratin types simple epithelia Neutral/Basic (B, class II) Acidic (A, class I) Squamous epithelia: suprabasal, keratinizing suprabasal, nonkeratinizing () () basal cells ( 1 tonsil, 2 mucosa) () 1 () 12 () 1 () 1 Transit. epith.: superficial cells intermed. / 3 basal cells Mesothelium () 3 () 3 () 3 () Bronchus, breast, prost., cerv.: basal/myoepithelial cells luminal cells Biliary/pancr. ducts, lung alv., endometr., renal collect. ducts 4 Stomach (foveola), intestine Hepatocytes, pancr. acini, prox. renal tubules Endocrine cells ( 5 Merkel, 6 thyr.) Smooth muscle (vasc., myom.), myofibrobl., 7 sm.ves.endothelia () 4 () 5 () 6 () 5 () 7 Mogens Vyberg, NordiQC 11
12 Cytokeratin types simple epithelia CK8: liver CK8: kidney Cytokeratin types simple epithelia Neutral/Basic (B, class II) Acidic (A, class I) Squamous epithelia: suprabasal, keratinizing suprabasal, nonkeratinizing () () basal cells ( 1 tonsil, 2 mucosa) () 1 () 12 () 1 () 1 Transit. epith.: superficial cells intermed. / 3 basal cells Mesothelium () 3 () 3 () 3 () Bronchus, breast, prost., cerv.: basal/myoepithelial cells luminal cells Biliary/pancr. ducts, lung alv., endometr., renal collect. ducts 4 Stomach (foveola), intestine Hepatocytes, pancr. acini, prox. renal tubules Endocrine cells ( 5 Merkel, 6 thyr.) Smooth muscle (vasc., myom.), myofibrobl., 7 sm.ves.endothelia () 4 () 5 () 6 () 5 () 7 Mogens Vyberg, NordiQC 12
13 Cytokeratin types simple epithelia Islet of Langerhans CK20: Merkel cells CK8: Pancreas Cytokeratin types mesenchymal cells Neutral/Basic (B, class II) Acidic (A, class I) Squamous epithelia: suprabasal, keratinizing suprabasal, nonkeratinizing () () basal cells ( 1 tonsil, 2 mucosa) () 1 () 12 () 1 () 1 Transit. epith.: superficial cells intermed. / 3 basal cells Mesothelium () 3 () 3 () 3 () Bronchus, breast, prost., cerv.: basal/myoepithelial cells luminal cells Biliary/pancr. ducts, lung alv., endometr., renal collect. ducts 4 Stomach (foveola), intestine Hepatocytes, pancr. acini, prox. renal tubules Endocrine cells ( 5 Merkel, 6 thyr.) Smooth muscle (vasc., myom.), myofibrobl., 7 sm.ves.endothelia () 4 () 5 () 6 () 5 () 7 Mogens Vyberg, NordiQC 13
14 Cytokeratin types mesenchymal cells CK7: endothelium CK8: lymph node fibroblastic reticulum cells Cytokeratins in squamous cell carcinoma Neutral/Basic (B, class II) Acidic (A, class I) Squamous cell carcinoma Transitional cell tumour Malignant mesothelioma Adenocarcinoma: complex epithelia (bronch., breast, prost.) Adenocarc.: biliary tract, pancr., endom., ovary Adenocarc.: stomach Adenocarc.: intestine Hepatocellular carcinoma Renal cell carcinoma Endocrine tumours: carcinoids Merkel cell carcinoma Thyroid carcinoma () () () () () () () Mogens Vyberg, NordiQC 14
15 Cytokeratins in squamous cell carcinoma esophagus CK5 CK4 Cytokeratins in squamous cell carcinoma CK13 CK4 (loss) Mogens Vyberg, NordiQC 15
16 Cytokeratins in squamous cell carcinoma CK7 (gain) CK8 (gain) Cytokeratins in urothelial carcinoma Neutral/Basic (B, class II) Acidic (A, class I) Squamous cell carcinoma Transitional cell tumour Malignant mesothelioma!! Adenocarcinoma: complex epithelia (bronch., breast, prost.) Adenocarc.: biliary tract, pancr., endom., ovary Adenocarc.: stomach Adenocarc.: intestine Hepatocellular carcinoma Renal cell carcinoma Endocrine tumours: carcinoids Merkel cell carcinoma Thyroid carcinoma () () () () () () () Mogens Vyberg, NordiQC 16
17 Cytokeratins in urothelial carcinoma CK20 CK5 CK20 CK5 Cytokeratins in malignant mesothelioma Neutral/Basic (B, class II) Acidic (A, class I) Squamous cell carcinoma Transitional cell tumour () () () () () Malignant mesothelioma Adenocarcinoma: complex epithelia (bronch., breast, prost.) Adenocarc.: biliary tract, pancr., endom., ovary Adenocarc.: stomach Adenocarc.: intestine Hepatocellular carcinoma Renal cell carcinoma Endocrine tumours: carcinoids Merkel cell carcinoma Thyroid carcinoma () () () () () () () Mogens Vyberg, NordiQC 17
18 Cytokeratins in malignant mesothelioma CK8 CK5 Cytokeratins in adenocarcinomas Neutral/Basic (B, class II) Acidic (A, class I) Squamous cell carcinoma Transitional cell tumour () () () () () Malignant mesothelioma Adenocarcinoma: complex epith. (bronch., breast, prost.) Adenocarc.: biliary tract, pancr., endom., ovary Adenocarc.: stomach Adenocarc.: intestine Hepatocellular carcinoma Renal cell carcinoma Endocrine tumours: carcinoids Merkel cell carcinoma Thyroid carcinoma () () () () () () () Mogens Vyberg, NordiQC 18
19 Cytokeratins in adenocarcinomas CK5: Breast lob. carcinoma CK5: Breast duct. carc. Cytokeratins in adenocarcinomas CK5: Prostate Breast lob. hyperplasia carcinoma CK5: prostate adenocarc. Mogens Vyberg, NordiQC 19
20 Cytokeratins in adenocarcinomas Neutral/Basic (B, class II) Acidic (A, class I) Squamous cell carcinoma Transitional cell tumour () () () () () Malignant mesothelioma Adenocarcinoma: complex epith. (bronch., breast, prost.) Adenocarc.: biliary tract, pancr., endom., ovary Adenocarc.: stomach Adenocarc.: intestine Hepatocellular carcinoma Renal cell carcinoma Endocrine tumours: carcinoids Merkel cell carcinoma Thyroid carcinoma () ()! () ()! () ()! ()! Cytokeratins in adenocarcinomas CK5: Serous ovarian carcinoma CK17 CK20: Gall bladder adenocarcinoma Mogens Vyberg, NordiQC 20
21 Cytokeratins in adenocarcinomas Neutral/Basic (B, class II) Acidic (A, class I) Squamous cell carcinoma Transitional cell tumour () () () () () Malignant mesothelioma Adenocarcinoma: complex epith. (bronch., breast, prost.) Adenocarc.: biliary tract, pancr., endom., ovary Adenocarc.: stomach Adenocarc.: intestine Hepatocellular carcinoma Renal cell carcinoma Endocrine tumours: carcinoids Merkel cell carcinoma Thyroid carcinoma () () () () () ()! () Cytokeratins in adenocarcinomas CK20 CK20 CK7 Colon: Typical Colon: Deviant CK7 Mogens Vyberg, NordiQC 21
22 Cytokeratins in adenocarcinomas Neutral/Basic (B, class II) Acidic (A, class I) Squamous cell carcinoma Transitional cell tumour () () () () () Malignant mesothelioma Adenocarcinoma: complex epith. (bronch., breast, prost.) Adenocarc.: biliary tract, pancr., endom., ovary Adenocarc.: stomach Adenocarc.: intestine Hepatocellular carcinoma Renal cell carcinoma Endocrine tumours: carcinoids Merkel cell carcinoma Thyroid carcinoma () () () () () () () Cytokeratins in adenocarcinomas HCC: typical CK7 CK7 HCC: deviant CK7 Mallory body CK20 Mogens Vyberg, NordiQC 22
23 Cytokeratins in endocrine tumours Neutral/Basic (B, class II) Acidic (A, class I) Squamous cell carcinoma Transitional cell tumour () () () () () Malignant mesothelioma Adenocarcinoma: complex epith. (bronch., breast, prost.) Adenocarc.: biliary tract, pancr., endom., ovary Adenocarc.: stomach Adenocarc.: intestine Hepatocellular carcinoma Renal cell carcinoma Endocr. tumours: carcinoids Merkel cell carcinoma Thyroid carcinoma () () () () () () () Cytokeratins in endocrine tumours CK20: Merkel cell carc. CK19: Thyr. papill. carc. Mogens Vyberg, NordiQC 23
24 Coordinate cytokeratin 7/20 expression CK20 CK20 amb CK20 Lung MBAC 1 Lung 1 Endom. c. CK7 Esophagus Biliary tract Breast d./l. Thyroid p./f. Cervix ad. Ovar. nonmuc Pancreas Ovary muc. CK7 amb Appendix Small intest. Urothelium Stomach Neuroend. 2 Germ cell t. 5 Rectum Colon Chr.phobe rc. 6 Carcinoid 2 Adrenal cort.c. CK7 Merkel cell 2 Liver cell c. Renal cell. c. 6 Prostate Coordinate cytokeratin 7/20 expression CK20 CK7 48, biopsy from vaginal polyp CK7 Mogens Vyberg, NordiQC 24
25 Coordinate cytokeratin 7/20 expression CK20 CK7 CK7 Coordinate cytokeratin 7/20 expression CK20 CK20 cdx2 CK7 CK7 CK7 Mogens Vyberg, NordiQC 25
26 Coordinate cytokeratin 7/20 expression CK7 CK20 Coordinate cytokeratin 7/20 expression CK20 CK20 amb CK20 Lung MBAC 1 Lung 1 Endom. c. CK7 Esophagus Biliary tract Breast d./l. Thyroid p./f. Cervix ad. Ovar. nonmuc Pancreas Ovary muc. CK7 amb Appendix Small intest. Urothelium Stomach Neuroend. 2 Germ cell t. 5 Rectum Colon Chr.phobe rc. 6 Carcinoid 2 Adrenal cort.c. CK7 Merkel cell 2 Liver cell c. Renal cell. c. 6 Prostate Mogens Vyberg, NordiQC 26
27 Coordinate cytokeratin 7/20 expression CK20 CK20 amb CK20 Lung MBAC 1 Lung 1 Endom. c. CK7 Esophagus Biliary tract Breast d./l. Thyroid p./f. Cervix ad. Ovar. nonmuc Pancreas Ovary muc. CK7 amb Appendix Small intest. Urothelium Stomach Neuroend. 2 Germ cell t. 5 Rectum Colon Chr.phobe rc. 6 Carcinoid 2 Adrenal cort.c. CK7 Merkel cell 2 Liver cell c. Renal cell. c. 6 Prostate Coordinate cytokeratin 7/20 expression CK7 CK20 CDX2 Mogens Vyberg, NordiQC 27
28 Coordinate cytokeratin 7/20 expression CK20 CK20 amb CK20 Lung MBAC 1 Lung 1 Endom. c. CK7 Esophagus Biliary tract Breast d./l. Thyroid p./f. Cervix ad. Ovar. nonmuc Pancreas Ovary muc. CK7 amb Appendix Small intest. Urothelium Stomach Neuroend. 2 Germ cell t. 5 Rectum Colon Chr.phobe rc. 6 Carcinoid 2 Adrenal cort.c. CK7 Merkel cell 2 Liver cell c. Renal cell. c. 6 Prostate Coordinate cytokeratin 7/20 expression Urothelial carcinoma CK20 CK7 Mogens Vyberg, NordiQC 28
29 Coordinate cytokeratin 7/20 expression CK20 CK20 amb CK20 Lung MBAC 1 Lung 1 Endom. c. CK7 Esophagus Biliary tract Breast d./l. Thyroid p./f. Cervix ad. Ovar. nonmuc Pancreas Ovary muc. CK7 amb Appendix Small intest. Urothelium Stomach Neuroend. 2 Germ cell t. 5 Rectum Colon Chr.phobe rc. 6 Carcinoid 2 Adrenal cort.c. CK7 Merkel cell 2 Liver cell c. Renal cell. c. 6 Prostate Cytokeratins which clone? CKs in colon adenoc. 34 E12 (CK1,10,5,14) CK5/6 CK14 CK17 CK: renal cell carcinoma Mogens Vyberg, NordiQC 29
30 Cytokeratins: Selection of antibodies optimal too diluted HIER Prot. CK5/6: clone D5/16 B4 CK5: XM26 CK5/14/1/10/19?: 34BE12 Cytokeratins which clone MNF 116 AE1/AE3 KL1 CK 5, 6, 8, 17, 19 CK 1, 4, 5, 6, 8, 10, 14, 16,19 CK (5), 6, 8, 10,18,19 Normal skin squamous cell carcinoma Mogens Vyberg, NordiQC 30
31 Cytokeratins which clone MNF 116 AE1/AE3 KL1 CK 5, 6, 8, 17, 19 CK 1, 4, 5, 6, 8, 10, 14, 16,19 CK (5), 6, 8, 10,18,19 Normal liver hepatocellular carcinoma Inappropriate package inserts CKLMW Specificity Protocols CK types Vendor: recomm. Aalborg 5D Thermo: Trypsin TE TS1 8 Thermo: Ci ph 6 TE DC10 18 NC: High temp. TE C ZM: Ci ph6 / Pepsin NC: High t. / Trypsin TE CAM (7) BD: Trypsin II Prot. K 35BH11 8 DAKO: Prot /heat Thermo: Pepsin TE Mogens Vyberg, NordiQC 31
32 Inappropriate epitope retrieval CK8: 35BH11 Pepsin Proteinase K HIER TE9 Inappropriate epitope retrieval CK8: 35BH11 1:40 Proteinase K 1:50 HIER TE9 1:20 1:25 Mogens Vyberg, NordiQC 32
33 Cytokeratins: Selection of antibodies Esophagus optimal CK19: clone A53B/A2.26 CK19: clone RCK108 After proteolysis as recommended by the vendor Cytokeratins: Selection of antibodies Papillary optimal thyroid carcinoma CK19: clone A53B/A2.26 CK19: clone RCK108 After proteolysis as recommended by the vendor Mogens Vyberg, NordiQC 33
34 General epithelial markers Epithelial cell adhesion molecule (EpCAM) Epithelial membrane antigen EpCAM Glycoproteins located on the cell membrane surface (preferentially basolaterally) and in the cytoplasm of virtually all epithelial cells with the exception of squamous epithelia (mucosae focal pos.) hepatocytes (pos. with inflammation and fibrosis) renal proximal tubular cells gastric parietal cells some endocrine cells Also negative mesothelial cells (pos. with reactive changes). mesenchymal cells germ cells neural crest cells (except. olfactory neurons) Mogens Vyberg, NordiQC 34
35 EpCAM Liver HCC EpCAM Undiff carcinoma Mogens Vyberg, NordiQC 35
36 EpCAM Choroid plexus pap. Malignant mesothelioma EMA (MUC1) Group of heavily glycosylated transmembrane proteins, related to the high molecular weight glycoproteins of human milk fat globule (HMFG). Present in a variety of glandular (secretory) epithelia: breast eccrine and apocrine glands pancreas Present in nonsecretory epithelia: urothelium renal collecting tubules squamous epithelium Mogens Vyberg, NordiQC 36
37 EMA (MUC1) Little or no EMA is expressed in gastrointestinal epithelium endocervical epithelium prostate epididymis and rete testis germ cells hepatocytes adrenal cortical cells thyroid follicular epithelium EMA (MUC1) EMA positive nonepithelial cells mesothelium, (membr., when reactively changed) arachnoid cells, ependyma, choroid plexus perineural fibroblastic cells activated Bcells, plasma cells Mogens Vyberg, NordiQC 37
38 Immunohistochemical classification of exocrine adenocarcinomas of unknown origin Adenocarcinomas of the unknown primary: Planning Consider the likelihood of an origin Morphology Age and sex Clinical information, imaging.... Select antibodies for a diagnostic algorithm: Primary and secondary antibody panels Turnaroundtime Laboratory expenses Interpret the stains in a proper context Mogens Vyberg, NordiQC 38
39 Secondary panels for carcinoma identification/subclassification Cytokeratin subtypes Oncofetal proteins Transcription factors Neuroendocrine proteins Hormone receptors Secretory proteins Cell adhesion molecules... Breast markers Lung markers GImarkers Fem.gen.tract markers Urinary tract markers Mesothelial markers Endocrine markers Prostate markers JK Generel epithelial markers CK: renal cell carcinoma Breast markers Estrogen receptor Gross cystic disease FP15 Mammaglobin Mogens Vyberg, NordiQC 39
40 Estrogen receptor alpha Estrogen sensitive tissues: Breast Ovarium Fallopian tube Endo and myometrium Uterine cervix Thyroid gland Pituitary gland Pancreas Sweat gland Salivary gland Prostate Estrogen receptor alpha Adenocarcinomas Breast carcinoma / Ovarian (nonmuc.) / Endometrial carc. / Cervix, lung, kidney, endocrine... / ERα Sica et al. APLM 132,1889,2008 Mogens Vyberg, NordiQC 40
41 Estrogen receptor alpha Lung adenocarcinomas ERα Sica et al. APLM 132,1889,2008 Estrogen receptor alpha in lung adenocarcinoma TTF Napsin ER Mogens Vyberg, NordiQC 41
42 Estrogen receptor alpha: The influence of antibody selection 92 lung adenocarcinomas ER ( 1% pos. cells) ERα 1D5: 8% 6F11: 14% SP1: 27% GomezFernandez et al. AIMM 2010;18:137 GCDFP15 (gross cystic disease fluid protein 15) Prolactin induced glycoprotein of apocrine cells Adenocarcinomas Breast / Sweat gland / Salivary gland / Lung () Renal cell () Ovary () GCDFP15 in sweat glands Mogens Vyberg, NordiQC 42
43 GCDFP15 Breast carcinomas Gastric biopsies, 43 y ER GCDFP15 Mogens Vyberg, NordiQC 43
44 Mammaglobin Mammaryspecific member of the uteroglobin family Adenocarcinomas Breast / Sweat gland / Salivary gland / Lung / Stomach, biliary, thyroid, ovary, endom. () Mammaglobin in breast Mammaglobin Breast ductal carcinomas Mogens Vyberg, NordiQC 44
45 61, metastatic adenocarcinoma in the eye lid 61, metastatic adenocarcinoma in the eye lid: Moll gland ca. MAMMAGLOBIN Mogens Vyberg, NordiQC 45
46 Lung markers Thyroid transcription factor1 Napsin A Thyroid transcription factor1 Nuclear gene regulating protein Thyroid gland: regulating thyroglobulin, thyroperoxidase and thyrotropin receptor. Lung: regulating surfactant proteins and Clara cell secretory protein. Thyroid follicles and Ccells Lung pneumocytes II and Clara cells Brain Pituitary Parathyroid Normal lung Mogens Vyberg, NordiQC 46
47 Thyroid transcription factor1 Lung adenocarcinoma Urothelial carcinoma Thyroid transcription factor1 SCLC in liver, clone 8G7G3/1 Mogens Vyberg, NordiQC 47
48 Thyroid transcription factor1 Lung adenocarcinoma large cell carcinoma small cell carcinoma carcinoid % pos.: SPT G7G3/ squamous cell carcinoma Nonlung small cell carcinoma Thyroid carc. (nonanaplastic) Nonlung carcinomas Nonlung carcinoids ~ 0 0? ~ 0 Matoso et al, AIMM 2010,18: Napsin A Aspartic proteinase Type II pneumocytes Proximal and convoluted renal tubules (Pancreatic acini and ducts) Mogens Vyberg, NordiQC 48
49 Napsin A Aspartic proteinase Type II pneumocytes Proximal and convoluted renal tubules (Pancreatic acini and ducts) Napsin A: lung adenocarcinoma ~ 80% Mogens Vyberg, NordiQC 49
50 Napsin A: Lung squamous carcinoma 0 30% Napsin A: Renal cell carcinoma 0 70% Mogens Vyberg, NordiQC 50
51 49 Liver adenocarcinoma of unknown primary CK20 49 Liver adenocarcinoma of unknown primary: Lung TTF Napsin A Mogens Vyberg, NordiQC 51
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