Cytokeratins and other epithelial markers dth ithlil k in...
Transcript of Cytokeratins and other epithelial markers dth ithlil k in...
Cytokeratins and other epithelail markers
Mogens Vyberg 2013 1
CIQC/CAP-ACP SEMINAR 2013:DIAGNOSTIC IHCAND MOLECULAR PATHOLOGY
Cytokeratins d th ith li l k
Mogens Vyberg
Aalborg University HospitalDenmark
and other epithelial markers in diagnostic IHC
• Highly complex family of intermediate filaments
• > 50 distinct types (excl. trichocytic keratins)
• Types CK1-20 diagnostically most relevant:
Class I (type A - Acidic):
CK9 (64 kD ) CK20 (40 kD )
Cytokeratins – a multigene family
CK9 (64 kDa) - CK20 (40 kDa)
Class II (type B - Basic/neutral):
CK1 (68 kDa) - CK8 (52.5 kDa)
(B) (A)
The Moll Cytokeratin catalogue 1982
CK: renal cell carcinoma
1992
11?
Moll et al. Cell 1982; 31:11
Cytokeratins and other epithelail markers
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• One CK class I and one CK class II ‘always’ paired
• CK class I in a pair ~ 8 kDa smaller than class II
Pairing of cytokeratins
Modified from: Lane & Alexander Semin Cancer Biol 1990, 1:165
Neutral/Basic (B, class II)Acidic (A, class I)
413
514 17 19
720
818
Squamous epithelia:- suprabasal, keratinizing - - + ++ (+) - - - -- suprabasal, non-keratinizing +++ +++ + ++ (+) - - - -
- basal cells (1tonsil, 2mucosa) - - +++ +++ (+)1 (++)12 (+)1 - (+)1
Transit. epith.: superficial cells - - - - - +++ +++ ++ +++
- intermed. / 3basal cells (+)3 +++ (+++)3 - (++)3 +++ +++ (+) +++Mesothelium ++ ++ + +++ +++ +++
Cytokeratin types and cell types
Mesothelium - - ++ ++ + +++ +++ - +++
Bronchus, breast, prost., cerv.:- basal/myoepithelial cells - - +++ ++ +++ ++ - - -- luminal cells - - + + + +++ +++ - +++
Biliary/pancr. ducts, lung alv.,endometr., renal collect. ducts - - - - - +++ +++ - +++4Stomach (foveola), intestine - - - - - +++ (+)4 +++ +++Hepatocytes, pancr. acini,prox. renal tubules - - - - - - - - +++Endocrine cells (5Merkel, 6thyr.) - - - - - (+++)5 (++)6 (+++)5 +++Smooth muscle (vasc., myom.),myofibrobl., 7sm.ves.endothelia - - - - - + (++)7 - ++
HMW Cytokeratin types - squamous epithelia
Neutral/Basic (B, class II)Acidic (A, class I)
413
514 17 19
720
818
Squamous epithelia:- suprabasal, keratinizing - - + ++ (+) - - - -- suprabasal, non-keratinizing +++ +++ + ++ (+) - - - -
- basal cells (1tonsil, 2mucosa) - - +++ +++ (+)1 (++)12 (+)1 - (+)1
Transit. epith.: superficial cells - - - - - +++ +++ ++ +++
- intermed. / 3basal cells (+)3 +++ (+++)3 - (++)3 +++ +++ (+) +++Mesothelium ++ ++ + +++ +++ +++Mesothelium - - ++ ++ + +++ +++ - +++
Bronchus, breast, prost., cerv.:- basal/myoepithelial cells - - +++ ++ +++ ++ - - -- luminal cells - - + + + +++ +++ - +++
Biliary/pancr. ducts, lung alv.,endometr., renal collect. ducts - - - - - +++ +++ - +++4Stomach (foveola), intestine - - - - - +++ (+)4 +++ +++Hepatocytes, pancr. acini,prox. renal tubules - - - - - - - - +++Endocrine cells (5Merkel, 6thyr.) - - - - - (+++)5 (++)6 (+++)5 +++Smooth muscle (vasc., myom.),myofibrobl., 7sm.ves.endothelia - - - - - + (++)7 - ++
Cytokeratins and other epithelail markers
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HMW Cytokeratin types - squamous epithelia
CK5: esophagus CK4: esophagus
HMW Cytokeratin types - squamous epithelia
CK17: tonsil CK17: skin
LMW Cytokeratin types - squamous epithelia
Neutral/Basic (B, class II)Acidic (A, class I)
413
514 17 19
720
818
Squamous epithelia:- suprabasal, keratinizing - - + ++ (+) - - - -- suprabasal, non-keratinizing +++ +++ + ++ (+) - - - -
- basal cells (1tonsil, 2mucosa) - - +++ +++ (+)1 (++)2 (+)1 - (+)1
Transit. epith.: superficial cells - - - - - +++ +++ ++ +++
- intermed. / 3basal cells (+)3 +++ (+++)3 - (++)3 +++ +++ (+) +++Mesothelial cells ++ ++ + +++ +++ +++Mesothelial cells - - ++ ++ + +++ +++ - +++
Bronchus, breast, prost., cerv.:- basal/myoepithelial cells - - +++ ++ +++ ++ - - -- luminal cells - - + + + +++ +++ - +++
Biliary/pancr. ducts, lung alv.,endometr., renal collect. ducts - - - - - +++ +++ - +++4Stomach (foveola), intestine - - - - - +++ (+)4 +++ +++Hepatocytes, pancr. acini,prox. renal tubules - - - - - - - - +++Endocrine cells (5Merkel, 6thyr.) - - - - - (+++)5 (++)6 (+++)5 +++Smooth muscle (vasc., myom.),myofibrobl., 7sm.ves.endothelia - - - - - + (++)7 - ++
Cytokeratins and other epithelail markers
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LMW Cytokeratin types - squamous epithelia
CK19: tonsil CK19: esophagus
Cytokeratin types - urothelium
Neutral/Basic (B, class II)Acidic (A, class I)
413
514 17 19
720
818
Squamous epithelia:- suprabasal, keratinizing - - + ++ (+) - - - -- suprabasal, non-keratinizing +++ +++ + ++ (+) - - - -
- basal cells (1tonsil, 2mucosa) - - +++ +++ (+)1 (++)12 (+)1 - (+)1
Transit. epith.: superficial cells - - - - - +++ +++ ++ +++- intermed. / 3basal cells (+)3 +++ (+++)3 - (++)3 +++ +++ (+) +++
Mesothelium ++ ++ + +++ +++ +++Mesothelium - - ++ ++ + +++ +++ - +++
Bronchus, breast, prost., cerv.:- basal/myoepithelial cells - - +++ ++ +++ ++ - - -- luminal cells - - + + + +++ +++ - +++
Biliary/pancr. ducts, lung alv.,endometr., renal collect. ducts - - - - - +++ +++ - +++4Stomach (foveola), intestine - - - - - +++ (+)4 +++ +++Hepatocytes, pancr. acini,prox. renal tubules - - - - - - - - +++Endocrine cells (5Merkel, 6thyr.) - - - - - (+++)5 (++)6 (+++)5 +++Smooth muscle (vasc., myom.),myofibrobl., 7sm.ves.endothelia - - - - - + (++)7 - ++
Cytokeratin types - urothelium
CK5 (+CK13) CK20
Cytokeratins and other epithelail markers
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Cytokeratin types - mesotheliumNeutral/Basic (B, class II)Acidic (A, class I)
413
514 17 19
720
818
Squamous epithelia:- suprabasal, keratinizing - - + ++ (+) - - - -- suprabasal, non-keratiniz.ep. +++ +++ + ++ (+) - - - -
- basal cells (1tonsil, 2mucosa) - - +++ +++ (+)1 (++)12 (+)1 - (+)1
Transit. epith.: superficial cells - - - - - +++ +++ ++ +++
- intermed. / 3basal cells (+)3 +++ (+++)3 - (++)3 +++ +++ (+) +++Mesothelium ++ ++ + +++ +++ +++Mesothelium - - ++ ++ + +++ +++ - +++
Bronchus, breast, prost., cerv.:- basal/myoepithelial cells - - +++ ++ +++ ++ - - -- luminal cells - - + + + +++ +++ - +++
Biliary/pancr. ducts, lung alv.,endometr., renal collect. ducts - - - - - +++ +++ - +++4Stomach (foveola), intestine - - - - - +++ (+)4 +++ +++Hepatocytes, pancr. acini,prox. renal tubules - - - - - - - - +++Endocrine cells (5Merkel, 6thyr.) - - - - - (+++)5 (++)6 (+++)5 +++Smooth muscle (vasc., myom.),myofibrobl., 7sm.ves.endothelia - - - - - + (++)7 - ++
Cytokeratin types - mesothelium
CK5: mesothelium(adenocarcinoma neg.)CK19: mesothelium
Cytokeratin types - complex epithelia
Neutral/Basic (B, class II)Acidic (A, class I)
413
514 17 19
720
818
Squamous epithelia:- suprabasal, keratinizing - - + ++ (+) - - - -- suprabasal, non-keratinizing +++ +++ + ++ (+) - - - -
- basal cells (1tonsil, 2mucosa) - - - +++ (+)1 (++)12 (+)1 - (+)1
Transit. epith.: superficial cells - - - - - +++ +++ ++ +++
- intermed. / 3basal cells (+)3 +++ (+++)3 - (++)3 +++ +++ (+) +++Mesothelium ++ ++ + +++ +++ +++Mesothelium - - ++ ++ + +++ +++ - +++
Bronchus, breast, prost., cerv.:- basal/myoepithelial cells - - +++ ++ +++ ++ - - -- luminal cells - - + + + +++ +++ - +++
Biliary/pancr. ducts, lung alv.,endometr., renal collect. ducts - - - - - +++ +++ - +++4Stomach (foveola), intestine - - - - - +++ (+)4 +++ +++Hepatocytes, pancr. acini,prox. renal tubules - - - - - - - - +++Endocrine cells (5Merkel, 6thyr.) - - - - - (+++)5 (++)6 (+++)5 +++Smooth muscle (vasc., myom.),myofibrobl., 7sm.ves.endothelia - - - - - + (++)7 - ++
Cytokeratins and other epithelail markers
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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)
413
514 17 19
720
818
Squamous epithelia:- suprabasal, keratinizing - - + ++ -(+) - - - -- suprabasal, non-keratinizing +++ +++ + ++ (+) - - - -
- basal cells (1tonsil, 2mucosa) - - - +++ -(+)1 (++)12 -(+)1 - -(+)1
Transit. epith.: superficial cells - - - - - +++ +++ ++ +++
- intermed. / 3basal cells (+)3 +++ (+++)3 - (++)3 +++ +++ (+) +++Mesothelium ++ ++ + +++ +++ +++Mesothelium - - ++ ++ + +++ +++ - +++
Bronchus, breast, prost., cerv.:- basal/myoepithelial cells - - +++ ++ +++ ++ - - -- luminal cells - - + + + +++ +++ - +++
Biliary/pancr. ducts, lung alv.,endometr., renal collect. ducts - - - - - +++ +++ - +++4Stomach (foveola), intestine - - - - - +++ (+)4 +++ +++Hepatocytes, pancr. acini,prox. renal tubules - - - - - - - - +++Endocrine cells (5Merkel, 6thyr.) - - - - - (+++)5 (++)6 (+++)5 +++Smooth muscle (vasc., myom.),myofibrobl., 7sm.ves.endothelia - - - - - + (++)7 - ++
Cytokeratin types - simple epithelia (liver, kidney)
CK7(19): bile ducts CK7(19): renal col.
Cytokeratins and other epithelail markers
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Cytokeratin types - simple epithelia
Neutral/Basic (B, class II)Acidic (A, class I)
413
514 17 19
720
818
Squamous epithelia:- suprabasal, keratinizing - - + ++ -(+) - - - -- suprabasal, non-keratinizing +++ +++ + ++ (+) - - - -
- basal cells (1tonsil, 2mucosa) - - - +++ -(+)1 (++)12 -(+)1 - -(+)1
Transit. epith.: superficial cells - - - - - +++ +++ ++ +++
- intermed. / 3basal cells (+)3 +++ (+++)3 - (++)3 +++ +++ (+) +++Mesothelium ++ ++ + +++ +++ +++Mesothelium - - ++ ++ + +++ +++ - +++
Bronchus, breast, prost., cerv.:- basal/myoepithelial cells - - +++ ++ +++ ++ - - -- luminal cells - - + + + +++ +++ - +++
Biliary/pancr. ducts, lung alv.,endometr., renal collect. ducts - - - - - +++ +++ - +++4Stomach (foveola), intestine - - - - - +++ (+)4 +++ +++Hepatocytes, pancr. acini,prox. renal tubules - - - - - - - - +++Endocrine cells (5Merkel, 6thyr.) - - - - - (+++)5 (++)6 (+++)5 +++Smooth muscle (vasc., myom.),myofibrobl., 7sm.ves.endothelia - - - - - + (++)7 - ++
Cytokeratin types - simple epithelia
CK20: gastric foveolae CK20: colon
Cytokeratin types - simple epithelia
Neutral/Basic (B, class II)Acidic (A, class I)
413
514 17 19
720
818
Squamous epithelia:- suprabasal, keratinizing - - + ++ -(+) - - - -- suprabasal, non-keratinizing +++ +++ + ++ (+) - - - -
- basal cells (1tonsil, 2mucosa) - - - +++ -(+)1 (++)12 -(+)1 - -(+)1
Transit. epith.: superficial cells - - - - - +++ +++ ++ +++
- intermed. / 3basal cells (+)3 +++ (+++)3 - (++)3 +++ +++ (+) +++Mesothelium ++ ++ + +++ +++ +++Mesothelium - - ++ ++ + +++ +++ - +++
Bronchus, breast, prost., cerv.:- basal/myoepithelial cells - - +++ ++ +++ ++ - - -- luminal cells - - + + + +++ +++ - +++
Biliary/pancr. ducts, lung alv.,endometr., renal collect. ducts - - - - - +++ +++ - +++4Stomach (foveola), intestine - - - - - +++ (+)4 +++ +++Hepatocytes, pancr. acini,prox. renal tubules - - - - - - - - +++Endocrine cells (5Merkel, 6thyr.) - - - - - (+++)5 (++)6 (+++)5 +++Smooth muscle (vasc., myom.),myofibrobl., 7sm.ves.endothelia - - - - - + (++)7 - ++
Cytokeratins and other epithelail markers
Mogens Vyberg 2013 8
Cytokeratin types - simple epithelia
CK8: liver CK8: kidney
Cytokeratin types - simple epithelia
Neutral/Basic (B, class II)Acidic (A, class I)
413
514 17 19
720
818
Squamous epithelia:- suprabasal, keratinizing - - + ++ -(+) - - - -- suprabasal, non-keratinizing +++ +++ + ++ (+) - - - -
- basal cells (1tonsil, 2mucosa) - - - +++ -(+)1 (++)12 -(+)1 - -(+)1
Transit. epith.: superficial cells - - - - - +++ +++ ++ +++
- intermed. / 3basal cells (+)3 +++ (+++)3 - (++)3 +++ +++ (+) +++Mesothelium ++ ++ + +++ +++ +++Mesothelium - - ++ ++ + +++ +++ - +++
Bronchus, breast, prost., cerv.:- basal/myoepithelial cells - - +++ ++ +++ ++ - - -- luminal cells - - + + + +++ +++ - +++
Biliary/pancr. ducts, lung alv.,endometr., renal collect. ducts - - - - - +++ +++ - +++4Stomach (foveola), intestine - - - - - +++ (+)4 +++ +++Hepatocytes, pancr. acini,prox. renal tubules - - - - - - - - +++Endocrine cells (5Merkel, 6thyr.) - - - - - (+++)5 (++)6 (+++)5 +++Smooth muscle (vasc., myom.),myofibrobl., 7sm.ves.endothelia - - - - - + (++)7 - ++
Cytokeratin types - simple epithelia
CK20: Merkel cells CK8: Pancreas
Islet of Langerhans
Cytokeratins and other epithelail markers
Mogens Vyberg 2013 9
Cytokeratin types - mesenchymal cells
Neutral/Basic (B, class II)Acidic (A, class I)
413
514 17 19
720
818
Squamous epithelia:- suprabasal, keratinizing - - + ++ -(+) - - - -- suprabasal, non-keratinizing +++ +++ + ++ (+) - - - -
- basal cells (1tonsil, 2mucosa) - - - +++ -(+)1 (++)12 -(+)1 - -(+)1
Transit. epith.: superficial cells - - - - - +++ +++ ++ +++
- intermed. / 3basal cells (+)3 +++ (+++)3 - (++)3 +++ +++ (+) +++Mesothelium ++ ++ + +++ +++ +++Mesothelium - - ++ ++ + +++ +++ - +++
Bronchus, breast, prost., cerv.:- basal/myoepithelial cells - - +++ ++ +++ ++ - - -- luminal cells - - + + + +++ +++ - +++
Biliary/pancr. ducts, lung alv.,endometr., renal collect. ducts - - - - - +++ +++ - +++4Stomach (foveola), intestine - - - - - +++ (+)4 +++ +++Hepatocytes, pancr. acini,prox. renal tubules - - - - - - - - +++Endocrine cells (5Merkel, 6thyr.) - - - - - (+++)5 (++)6 (+++)5 +++Smooth muscle (vasc., myom.),myofibrobl., 7sm.ves.endothelia - - - - - + (++)7 - ++
Cytokeratin types - mesenchymal cells
CK7: endotheliumCK8: lymph node fibroblastic reticulum cells
Neutral/Basic (B, class II)Acidic (A, class I)
413
514 17 19
720
818
Squamous cell carcinoma + + ++ ++ (+) (+) (+) - (+)Transitional cell tumour + + + + + ++ ++ ++ ++
Malignant mesothelioma - - ++ ++ + ++ + - ++
Adenocarcinoma: complexepithelia (bronch., breast, prost.) - - (+) (+) (+) ++ ++ - ++Adenocarc.: biliary tract,
Cytokeratins in epithelial neoplasias
pancr., endom., ovary - - (+) (+) (+) ++ ++ (+) ++Adenocarc.: stomach - - - - - ++ + + ++Adenocarc.: intestine - - - - - ++ + ++ ++Hepatocellular carcinomaRenal cell carcinoma - - - - - - + - ++Endocrine tumours: carcinoids - - - - - + + - ++- Merkel cell carcinoma - - - - - + - ++ ++- Thyroid carcinoma - - - - - + ++ - ++
Cytokeratins and other epithelail markers
Mogens Vyberg 2013 10
Neutral/Basic (B, class II)Acidic (A, class I)
413
514 17 19
720
818
Squamous cell carcinoma + + ++ ++ + + + - +Transitional cell tumour + + + + + ++ ++ ++ ++
Malignant mesothelioma - - ++ ++ + ++ + - ++
Adenocarcinoma: complexepithelia (bronch., breast, prost.) - - (+) (+) (+) ++ ++ - ++Adenocarc.: biliary tract,
Cytokeratins in squamous cell carcinoma
pancr., endom., ovary - - (+) (+) (+) ++ ++ (+) ++Adenocarc.: stomach - - - - - ++ + + ++Adenocarc.: intestine - - - - - ++ + ++ ++Hepatocellular carcinomaRenal cell carcinoma - - - - - - + - ++Endocrine tumours: carcinoids - - - - - + + - ++- Merkel cell carcinoma - - - - - + - ++ ++- Thyroid carcinoma - - - - - + ++ - ++
esophagus
Cytokeratins in squamous cell carcinoma
CK4CK5
Cytokeratins in squamous cell carcinoma
CK13 CK4 (loss)
Cytokeratins and other epithelail markers
Mogens Vyberg 2013 11
Cytokeratins in squamous cell carcinoma
CK7 (gain) CK8 (gain)
Neutral/Basic (B, class II)Acidic (A, class I)
413
514 17 19
720
818
Squamous cell carcinoma + + ++ ++ + + + - +Transitional cell tumour + + ++ + ! + ! ++ ++ ++ ++Malignant mesothelioma - - ++ ++ + ++ + - ++
Adenocarcinoma: complexepithelia (bronch., breast, prost.) - - (+) (+) (+) ++ ++ - ++Adenocarc.: biliary tract,
Cytokeratins in urothelial carcinoma
pancr., endom., ovary - - (+) (+) (+) ++ ++ (+) ++Adenocarc.: stomach - - - - - ++ + + ++Adenocarc.: intestine - - - - - ++ + ++ ++Hepatocellular carcinomaRenal cell carcinoma - - - - - - + - ++Endocrine tumours: carcinoids - - - - - + + - ++- Merkel cell carcinoma - - - - - + - ++ ++- Thyroid carcinoma - - - - - + ++ - ++
Cytokeratins in urothelial carcinoma
CK20
CK20 CK5
CK5
Cytokeratins and other epithelail markers
Mogens Vyberg 2013 12
Neutral/Basic (B, class II)Acidic (A, class I)
413
514 17 19
720
818
Squamous cell carcinoma + + ++ ++ (+) (+) (+) - (+)Transitional cell tumour + + + + + ++ ++ ++ ++
Malignant mesothelioma - - ++ ++ + ++ + - ++Adenocarcinoma: complexepithelia (bronch., breast, prost.) - - (+) (+) (+) ++ ++ - ++Adenocarc.: biliary tract,
Cytokeratins in malignant mesothelioma
pancr., endom., ovary - - (+) (+) (+) ++ ++ (+) ++Adenocarc.: stomach - - - - - ++ + + ++Adenocarc.: intestine - - - - - ++ + ++ ++Hepatocellular carcinomaRenal cell carcinoma - - - - - - + - ++Endocrine tumours: carcinoids - - - - - + + - ++- Merkel cell carcinoma - - - - - + - ++ ++- Thyroid carcinoma - - - - - + ++ - ++
Cytokeratins in malignant mesothelioma
CK5CK5
CK8 (loss)
Cytokeratins in malignant mesothelioma
CK5
CK8 (loss)
CK7
Cytokeratins and other epithelail markers
Mogens Vyberg 2013 13
Neutral/Basic (B, class II)Acidic (A, class I)
413
514 17 19
720
818
Squamous cell carcinoma + + ++ ++ (+) (+) (+) - (+)Transitional cell tumour + + + + + ++ ++ ++ ++
Malignant mesothelioma - - ++ ++ + ++ + - ++
Adenocarcinoma: complexepith. (bronch., breast, prost.) - - (+) (+) (+) ++ ++ - ++Adenocarc.: biliary tract,
Cytokeratins in adenocarcinomas
pancr., endom., ovary - - (+) (+) (+) ++ ++ (+) ++Adenocarc.: stomach - - - - - ++ + + ++Adenocarc.: intestine - - - - - ++ + ++ ++Hepatocellular carcinomaRenal cell carcinoma - - - - - - + - ++Endocrine tumours: carcinoids - - - - - + + - ++- Merkel cell carcinoma - - - - - + - ++ ++- Thyroid carcinoma - - - - - + ++ - ++
Cytokeratins in adenocarcinomas
CK5: Breast lob. carcinoma CK5: Breast duct. carc.
Cytokeratins in adenocarcinomas
CK5: Breast lob. carcinoma CK5: prostate adenocarc.CK5: Prostate hyperplasia
Cytokeratins and other epithelail markers
Mogens Vyberg 2013 14
Neutral/Basic (B, class II)Acidic (A, class I)
413
514 17 19
720
818
Squamous cell carcinoma + + ++ ++ (+) (+) (+) - (+)Transitional cell tumour + + + + + ++ ++ ++ ++
Malignant mesothelioma - - ++ ++ + ++ + - ++
Adenocarcinoma: complexepith. (bronch., breast, prost.) - - (+) (+) (+) ++ ++ - ++Adenocarc.: biliary tract,
Cytokeratins in adenocarcinomas
pancr., endom., ovary - - (+) ! (+) ! (+) ! ++ ++ (+) ! ++Adenocarc.: stomach - - - - - ++ + + ++Adenocarc.: intestine - - - - - ++ + ++ ++Hepatocellular carcinomaRenal cell carcinoma - - - - - - + - ++Endocrine tumours: carcinoids - - - - - + + - ++- Merkel cell carcinoma - - - - - + - ++ ++- Thyroid carcinoma - - - - - + ++ - ++
Cytokeratins in adenocarcinomas
CK17: Pancreas adenocarcinoma
CK5: Biliary tract adenocarcinoma
Cytokeratins in adenocarcinomas
CK17CK5: Serous ovarian carcinoma
CK20: Gall bladder adenocarcinoma
Cytokeratins and other epithelail markers
Mogens Vyberg 2013 15
Neutral/Basic (B, class II)Acidic (A, class I)
413
514 17 19
720
818
Squamous cell carcinoma + + ++ ++ (+) (+) (+) - (+)Transitional cell tumour + + + + + ++ ++ ++ ++
Malignant mesothelioma - - ++ ++ + ++ + - ++
Adenocarcinoma: complexepith. (bronch., breast, prost.) - - (+) (+) (+) ++ ++ - ++Adenocarc.: biliary tract,
Cytokeratins in adenocarcinomas
pancr., endom., ovary - - (+) (+) (+) ++ ++ (+) ++Adenocarc.: stomach - - - - - ++ + + ++Adenocarc.: intestine - - - - - ++ + ! ++ ++Hepatocellular carcinomaRenal cell carcinoma - - - - - - + - ++Endocrine tumours: carcinoids - - - - - + + - ++- Merkel cell carcinoma - - - - - + - ++ ++- Thyroid carcinoma - - - - - + ++ - ++
CK20
CK20
Cytokeratins in adenocarcinomas
CK7CK7Colon: Typical Colon: Deviant
Neutral/Basic (B, class II)Acidic (A, class I)
413
514 17 19
720
818
Squamous cell carcinoma + + ++ ++ (+) (+) (+) - (+)Transitional cell tumour + + + + + ++ ++ ++ ++
Malignant mesothelioma - - ++ ++ + ++ + - ++
Adenocarcinoma: complexepith. (bronch., breast, prost.) - - (+) (+) (+) ++ ++ - ++Adenocarc.: biliary tract,
Cytokeratins in adenocarcinomas
pancr., endom., ovary - - (+) (+) (+) ++ ++ (+) ++Adenocarc.: stomach - - - - - ++ + + ++Adenocarc.: intestine - - - - - ++ + ++ ++Hepatocellular carcinomaRenal cell carcinoma - - - - - - + - ++Endocrine tumours: carcinoids - - - - - + + - ++- Merkel cell carcinoma - - - - - + - ++ ++- Thyroid carcinoma - - - - - + ++ - ++
Cytokeratins and other epithelail markers
Mogens Vyberg 2013 16
CK7CK7
Cytokeratins in adenocarcinomas
CK7HCC: typical HCC: deviant
CK20
Mallory body
CK7
CK7
Cytokeratins in adenocarcinomas
CK7: RCC CK7: RCC
Neutral/Basic (B, class II)Acidic (A, class I)
413
514 17 19
720
818
Squamous cell carcinoma + + ++ ++ (+) (+) (+) - (+)Transitional cell tumour + + + + + ++ ++ ++ ++
Malignant mesothelioma - - ++ ++ + ++ + - ++
Adenocarcinoma: complexepith. (bronch., breast, prost.) - - (+) (+) (+) ++ ++ - ++Adenocarc.: biliary tract,
Cytokeratins in endocrine tumours
pancr., endom., ovary - - (+) (+) (+) ++ ++ (+) ++Adenocarc.: stomach - - - - - ++ + + ++Adenocarc.: intestine - - - - - ++ + ++ ++Hepatocellular carcinomaRenal cell carcinoma - - - - - - + - ++Endocr. tumours: carcinoids - - - - - + + - ++- Merkel cell carcinoma - - - - - + - ++ ++- Thyroid carcinoma - - - - - + ++ - ++
Cytokeratins and other epithelail markers
Mogens Vyberg 2013 17
Cytokeratins in endocrine tumours
CK20: Merkel cell carc. CK19: Thyr. papill. carc.
CK20+ CK20 amb CK20-
CK7+
Lung MBAC1
EsophagusBiliary tractPancreasOvary muc.
Lung 1
Breast d./l.Thyroid p./f.
Endom. c.Cervix ad.Ovar. nonmuc
Coordinate cytokeratin 7/20 expression
Urothelium
CK7 ambAppendixSmall intest.Rectum
StomachNeuroend.2
Germ cell t.5
Chr.phobe rc.6
CK7-
ColonMerkel cell 2
Carcinoid 2
Liver cell c.Renal cell. c.6
Adrenal cort.c.Prostate
CK20+ CK20 amb CK20-
CK7+
Lung MBAC1
EsophagusBiliary tractPancreasOvary muc.
Lung 1
Breast d./l.Thyroid p./f.
Endom. c.Cervix ad.Ovar. nonmuc
Coordinate cytokeratin 7/20 expression
Urothelium
CK7 ambAppendixSmall intest.Rectum
StomachNeuroend.2
Germ cell t.5
Chr.phobe rc.6
CK7-
ColonMerkel cell 2
Carcinoid 2
Liver cell c.Renal cell. c.6
Adrenal cort.c.Prostate
Cytokeratins and other epithelail markers
Mogens Vyberg 2013 18
CK20
Coordinate cytokeratin 7/20 expression
CK7CK7♀ 48, biopsy from vaginal ”polyp”
CK20
Coordinate cytokeratin 7/20 expression
CK7CK7
CK20
CK20
Coordinate cytokeratin 7/20 expression
CK7CK7CK7
cdx2
Cytokeratins and other epithelail markers
Mogens Vyberg 2013 19
Coordinate cytokeratin 7/20 expression
CK7 CK20
CK20+ CK20 amb CK20-
CK7+
Lung MBAC1
EsophagusBiliary tractPancreasOvary muc.
Lung 1
Breast d./l.Thyroid p./f.
Endom. c.Cervix ad.Ovar. nonmuc
Coordinate cytokeratin 7/20 expression
Urothelium
CK7 ambAppendixSmall intest.Rectum
StomachNeuroend.2
Germ cell t.5
Chr.phobe rc.6
CK7-
ColonMerkel cell 2
Carcinoid 2
Liver cell c.Renal cell. c.6
Adrenal cort.c.Prostate
CK20+ CK20 amb CK20-
CK7+
Lung MBAC1
EsophagusBiliary tractPancreasOvary muc.
Lung 1
Breast d./l.Thyroid p./f.
Endom. c.Cervix ad.Ovar. nonmuc
Coordinate cytokeratin 7/20 expression
Urothelium
CK7 ambAppendixSmall intest.Rectum
StomachNeuroend.2
Germ cell t.5
Chr.phobe rc.6
CK7-
ColonMerkel cell 2
Carcinoid 2
Liver cell c.Renal cell. c.6
Adrenal cort.c.Prostate
Cytokeratins and other epithelail markers
Mogens Vyberg 2013 20
CK7CK7
Coordinate cytokeratin 7/20 expression
CK7CK7CK20
CDX2
CK20+ CK20 amb CK20-
CK7+
Lung MBAC1
EsophagusBiliary tractPancreasOvary muc.
Lung 1
Breast d./l.Thyroid p./f.
Endom. c.Cervix ad.Ovar. nonmuc
Coordinate cytokeratin 7/20 expression
Urothelium
CK7 ambAppendixSmall intest.Rectum
StomachNeuroend.2
Germ cell t.5
Chr.phobe rc.6
CK7-
ColonMerkel cell 2
Carcinoid 2
Liver cell c.Renal cell. c.6
Adrenal cort.c.Prostate
CK20
Urothelial carcinoma
Coordinate cytokeratin 7/20 expression
CK7
Cytokeratins and other epithelail markers
Mogens Vyberg 2013 21
CK20+ CK20 amb CK20-
CK7+
Lung MBAC1
EsophagusBiliary tractPancreasOvary muc.
Lung 1
Breast d./l.Thyroid p./f.
Endom. c.Cervix ad.Ovar. nonmuc
Coordinate cytokeratin 7/20 expression
Urothelium
CK7 ambAppendixSmall intest.Rectum
StomachNeuroend.2
Germ cell t.5
Chr.phobe rc.6
CK7-
ColonMerkel cell 2
Carcinoid 2
Liver cell c.Renal cell. c.6
Adrenal cort.c.Prostate
CK20+ CK20 amb CK20-
CK7+
Lung MBAC1
EsophagusBiliary tractPancreasOvary muc.
Lung 1
Breast d./l.Thyroid p./f.
Endom. c.Cervix ad.Ovar. nonmuc
Coordinate cytokeratin 7/20 expression
Urothelium
CK7 ambAppendixSmall intest.Rectum
StomachNeuroend.2
Germ cell t.5
Chr.phobe rc.6
CK7-
ColonMerkel cell 2
Carcinoid 2
Liver cell c.Renal cell. c.6
Adrenal cort.c.Prostate
Optimal: 11%Good: 13%Insuff.: 76%
Cytokeratins and other epithelail markers
Mogens Vyberg 2013 22
Cytokeratins: Selection of antibodies
optimal too diluted HIER Prot.
CK5: XM-26CK5/6: clone D5/16 B4
34BE12:CK5/14/1/10/19?
Conc. Abs: CK types N Optimal Good Bord. Poor Suff.1 Suff. OPS2
mAb clone 34BE12
1/5/10/14 (19?)
89 1 6 75 7 8 % 40 %
mAb clone D5/16B4 5/6 17 6 7 3 1 76 % 82 %
mAb clone XM26 5 6 4 1 1 0 83 % 83 %
CK-HMW run 32, 2011
CK 5 or CK5/6 34BE12
Cytokeratins and other epithelail markers
Mogens Vyberg 2013 23
Cytokeratins – which clones
5D3 35βH11C51
CAM5.2DC10
TS1
Cytokeratins: Selection of antibodies
optimalEsophagus
CK19 l A53 B/A2 26 CK19 l RCK108CK19: clone A53-B/A2.26 CK19: clone RCK108After proteolysis as recommended by the vendor
Papillary thyroid carcinoma
Cytokeratins and other epithelail markers
Mogens Vyberg 2013 24
Cancer Most relevant markers
Lung carcinoma TTF-1, Napsin
Breast carcinoma ER, Mammaglobin, GCDFP-15, GATA3
Colorectal carcinoma CK20, CDX2, CEA, Cadherin17
Prostate carcinoma PSA, Prostein
Malignant melanoma MSA MLA SOX10
Secondary panels for carcinoma identification/subclassification
Malignant melanoma MSA, MLA, SOX10
Non-muc. ovarian carcinoma CA125, WT1, PAX8
Urothelial carcinoma CK20, GATA3
Pancreatic carcinoma SMAD4
Hepatocellular carcinoma Glypican 3, Arginase, canCD66a, canCD10
Neuroendocrine carcinoma Synaptophysin, Chromogranin
Thyroid transcription factor-1
Lung adenocarcinoma 80 70
- large cell carcinoma 50 40
- small cell carcinoma 90 90
- carcinoid 60 20
SPT24 8G7G3/1% pos.:
- squamous cell carcinoma 15 0
Non-lung small cell carcinoma 20-40 ?
Thyroid carc. (non-anaplastic) 100 100
Non-lung carcinomas 0 - 5 0 - 5
Non-lung carcinoids ~ 0 ~ 0
Matoso et al, AIMM 2010,18:142-149
SPT24 8G7G3/1
1:100
1:25
1:100
Thyroid
Cytokeratins and other epithelail markers
Mogens Vyberg 2013 25
SPT24 8G7G3/1
1:100
SPT24
1:25
1:100
Lung adenocarcinoma
8G7G3/1
1:100
SPT24
1:25
1:100
Lung carcinoid
CDX-2 protein in adenocarcinoma
Colorectum +(–)Mucinous ovar. +(–)Esoph./Stom. +/–Mucinous lung +/–Pancr./biliary –/+
Colon adenocarcinoma
yProstate –(+)Urothelial –(+)Endometrioid –(+)
Yolk sac tumour +
Cytokeratins and other epithelail markers
Mogens Vyberg 2013 26
CDX2Normalcolon
EPR-CON EPR-RTUEPR = rmAb EPR2764Y
DAK-CDX2 AMT-28 CDX2-88
CDX2Normalpancreas
EPR-CON EPR-RTU
DAK-CDX2 AMT-28 CDX2-88
CDX2Colonadenocarc
EPR-CON EPR-RTU
DAK-CDX2 AMT-28 CDX2-88
Cytokeratins and other epithelail markers
Mogens Vyberg 2013 27
Carcinoembryonic antigen (CD66e)
Adhesion molecule espc. associated with intestine
Carcinoembryonic antigen (CD66e) in adenocarcinomas
Colorectal +Medull. thyroid +Pancreas/biliary tract +/–Stomach +/–Lung +/–Ovary, mucinous +/–Ovary non-muc –/+Ovary, non-muc. –/+Prostate –Kidney –Liver (!) –
metast. colon adenoc
Carcinoembryonic antigen – which antibody?
Cytokeratins and other epithelail markers
Mogens Vyberg 2013 28
Carcinoembryonic antigen – which antibody?
Normal liver
II-7 pAb / TF3H8-1
Carcinoembryonic antigen – which antibody?
Mal. mesothelioma
mAb II-7 pAb / TF3H8-1
Paired box transcription factors: PAX8
RCC Endometrioid carc.
Cytokeratins and other epithelail markers
Mogens Vyberg 2013 29
SMAD4: Loss in pancreaticbiliary carcinomas
Ep-CAM
CIQC/CAP-ACP SEMINAR 2013:DIAGNOSTIC IHCAND MOLECULAR PATHOLOGY
Cytokeratins and other epithelial markers
Mogens Vyberg
Aalborg University HospitalDenmark
in diagnostic IHC
Thank you for your attention