CK20

Expression in normal tissues

 Colon, Merkel cells, small intestine (AJSP 2004;28:1352), stomach
 Urothelium (umbrella cells, AJSP 2001;25:1074)
 Uterus

Expression in benign lesions or tumors

 Bladder intestinal metaplasia (Mod Path 2006;19:1395)
 Fibroepithelioma of Pinkus (Am J Dermatopathol 2007;29:7)
 GI carcinoid (25%)
 Hydatidiform mole (complete-100%, partial-50%, Gynecol Oncol 2002;87:34)
 Renal oncocytoma (dot-like pattern, J Histochem Cytochem 2001;49:919)

Expression in malignant tumors

 digestive carcinomas

• colorectal adenocarcinoma
  • The most common immunophenotype of colorectal adenocarcinoma is positivity for CK20 and negativity for CK7, which is a relatively specific staining pattern for colorectal origin.
  • However, up to 20% of the tumors may exhibit a CK7-positive/CK20 negative or CK7-negative/CK20-negative staining pattern.
  • It has been suggested that reduced or absent CK20 expression in colorectal carcinoma is associated with MSI-H.

• ampullary carcinoma (variable-AJSP 2005;29:359)
  *- Anal (variable-Br J Dermatol 2000;142:243, Cancer 2001;92:2045)
• Appendiceal epithelial neoplasms (benign and malignant, 100%, Hum Path 2005;36:1217)
  *- Biliary papillary tumors (benign and malignant, Hepatology 2006;44:1333)
• Gastric (18-31%, Appl Immunohistochem Mol Morphol 2006;14:303, reduced if high levels of microsatellite instability, AJSP 2004;28:712)
• Hepatoid adenocarcinoma (AJSP 2003;27:1302)

 hepatocellular carcinoma (20% positive, Hum Path 2005;36:1226)

 pulmonary mucinous adenocarcinoma (Hum Path 2002;33:915)

 Merkel cell carcinoma (dot like, references above)

• Merkel cell carcinoma can be distinguished from metastatic small cell carcinoma using antibodies to cytokeratin 20 and thyroid transcription factor 1. (11533085)
• dot-like CK20+

 Ovarian carcinomas (Mod Path 2006;19:1421)

 pancreatic ductal carcinoma (Cancer 2006;106:693)

 prostatic carcinoma (variable)

 sinonasal adenocarcinoma (50%, Archives 2007;131:530)

 small cell of major salivary glands (AJSP 2004;28:762), urothelial (references above)

 Paget disease (secondary only-Br J Dermatol 2000;142:243)

• vulvar Paget disease secondary to anorectal or urothelial carcinoma but not primary (Hum Path 2002;33:545)

 mucinous ovarian carcinoma

Negative labelling

 anal glands (Archives 2001;125:1074)
 inverted urothelial papilloma (Hum Path 2004;35:1499)

Use in diagnostic pathology

 CK7+/CK20+ tumors

• carcinomas of bile duct (extrahepatic/gallbladder, often, Pathol Res Pract 2003;199:65)
• lung-mucinous bronchioloalveolar (AJCP 2004;122:421)
• pancreas (Cancer 2006;106:693 but see Archives 2000;124:1196)
• Urothelium (often, Archives 2001;125:921, Hum Path 2002;33:1136)
• primary mucinous tumors of ovary (74%)
• upper GI tract (78%)
• endocervix (88%, AJSP 2006;30:1130)

 CK7+/CK20- tumors

• carcinomas of bile duct (intrahepatic, Pathol Res Pract 2003;199:65)
• breast (Ann Diagn Pathol 1999;3:350)
• endocervical and endometrial adenocarcinoma (Int J Gynecol Pathol 2002;21:4), esophagus (distal, AJSP 2002;26:1213)
• lung (not mucinous bronchioloalveolar, BMC Cancer 2006;6:31)
• salivary gland (Pathol Int 2005;55:386)
• thyroid (Appl Immunohistochem Mol Morphol 2000;8:189)
• mesothelioma (Cancer 2001;92:2727)

 CK7-/CK20+ tumors

• carcinoma of colon (particularly early stage, Hum Path 2005;36:275)
• CK20 is less sensitive for poorly differentiated colonic carcinoma (Chin J Physiol 2006;49:298)
• Primary mucinous tumors of lower GI tract (79%, AJSP 2006;30:1130)
• primary bladder adenocarcinomas (29%, AJSP 2001;25:1380)

 CK7-/CK20- tumors

• carcinomas of adrenal cortex (Mod Path 2000;13:962)
• prostate (Mod Path 2000;13:962)

Differential diagnosis

 Urothelial carcinoma

• CK20+ p53+ CD44- favors urothelial carcinoma in situ vs. reactive urothelium (AJSP 2001;25:1074)
• CIS shows CK20 staining of deep urothelial cells compared with surface cells only in non-neoplastic lesions (Appl Immunohistochem Mol Morphol 2006;14:260)
• CK20+ in voided urine by RT-PCR is sensitive and specific for bladder carcinoma (Clin Biochem 2004;37:803, J Egypt Natl Canc Inst 2006;18:82, but see J Urol 2003;169:86)
• In papillary urothelial neoplasms, CK20+ is associated with increasing tumor grade and stage in pTa and pT1 patients (Mod Path 2000;13:1315, free full text)

 primary lung carcinoma (CK7+/CK20-) VS metastatic colonic carcinoma to lung (CK7-/CK20+, BMC Cancer 2006;6:31)
 colorectal adenocarcinoma (80% are CK20+) VS poorly differentiated prostatic carcinoma (90% are CK20-) at biopsy (Archives 2007;131:599)
 Merkel cell carcinoma (CK20+ dot-like, TTF1-) VS metastatic small cell carcinoma of lung (CK20-, TTF1+, Am J Dermatopathol 2006;28:99)
 Anal carcinoma (CK7+/CK20-) VS downward growth of colorectal carcinoma (CK7-/CK20+, Archives 2001;125:1074)

 short segment Barrett’s VS cardiac intestinal metaplasia (World J Gastroenterol 2005;11:6360)

• May confirm Barrett’s mucosa, which has strong diffuse CK7+ surface and crypt epithelium, strong CK20+ surface and superficial crypt staining
• Interpretation is affected by fixative (Hum Path 2005;36:58, but see Mod Path 2002;15:611-free full text)

 Rathke cleft cysts and pituitary gland pars intermedia (CK8+, CK20+) VS craniopharyngioma (CK8-, CK20-, Archives 2002;126:1174)

 adenocarcinoma of distal esophagus (CK7+/CK19+: 90%, CK7+/CK20-: 74%) VS proximal stomach adenocarcinoma (CK7+/CK19+: 44%, CK7+/CK20-: 24%, AJSP 2002;26:1213)

 To detect occult nodal tumor cells in colorectal adenocarcinoma (Hum Path 2006;37:1259, Br J Cancer 2006;95:218)

Molecular biology

- RT-PCR to detect tumor cells of breast and colorectal carcinoma in blood (J Mol Diagn 2006;8:105)

 RT-PCR assessment in peritoneal wash may predict recurrence in gastric carcinoma (Oncol Rep 2007;17:667)