Cytokeratins and other epithelial markers dth ithlil k in...
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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
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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 - ++
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Cytokeratins and other epithelail markers
Mogens Vyberg 2013 3
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 - ++
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Cytokeratins and other epithelail markers
Mogens Vyberg 2013 4
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
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Cytokeratins and other epithelail markers
Mogens Vyberg 2013 5
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 - ++
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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.
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Cytokeratins and other epithelail markers
Mogens Vyberg 2013 7
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 - ++
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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
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Cytokeratins and other epithelail markers
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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 - - - - - + ++ - ++
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Cytokeratins and other epithelail markers
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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)
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Cytokeratins and other epithelail markers
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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
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Cytokeratins and other epithelail markers
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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
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Cytokeratins and other epithelail markers
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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
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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
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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 - - - - - + ++ - ++
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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 - - - - - + ++ - ++
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Cytokeratins and other epithelail markers
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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
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Cytokeratins and other epithelail markers
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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
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Cytokeratins and other epithelail markers
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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
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Cytokeratins and other epithelail markers
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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
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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%
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Cytokeratins and other epithelail markers
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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
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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
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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
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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 +
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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
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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?
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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.
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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