KRT7

Definition: CK7 is a type II keratin of simple nonkeratinizing epithelia. CK7is expressed in breast, lung, ovary and urothelium, but usually NOT in GI or stratified squamous epithelium.

CK7 expression in normal cells

 breast
 lung
 ovary
 urothelium
 biliary epithelial cells
 Anal glands and anal transition zone (Arch Pathol Lab Med 2001;125:1074)
 Bile ducts (Exp Cell Res 1987;170:235)
 Breast
 Cervical glands
 Endometrium
 Fallopian tube
 Fetal cells in transcervical mucus (J Obstet Gynaecol Res 2005;31:500)
 Gallbladder
 Kidney collecting ducts
 Lung
 Mesothelium
 Ovarian epithelium (Am J Pathol 1991;138:455)
 Pancreatic ducts (J Pathol 1998;184:234)
 Salivary gland acini (Mod Pathol 2004;17:803), intercalated ducts and intercalated duct lesions (Am J Surg Pathol 2009;33:1322)
 Thyroid epithelium
 Toker cells (Am J Dermatopathol 2005;27:185)
 Trophoblast (J Immunol Methods 2004;286:21)
 Urothelium (Eur J Cell Biol 2004;83:27)

CK7 expression in benign lesions

 Cystitis glandularis (bladder) of usual type (intestinal type is CK7-)
 Colonic serrated adenoma (Dig Dis Sci 2005;50:1741)
 Ependymoma: extra-axial (80%) versus CNS (10%, Am J Surg Pathol 2008;32:710)
 Esophagus-Barrett’s: strong diffuse CK7+ surface and crypt epithelium, strong CK20+ surface and superficial crypt staining; interpretation is affected by fixative (Hum Pathol 2005;36:58, but see Mod Pathol 2002;15:611); pattern may help distinguish short segment Barrett’s from cardiac intestinal metaplasia (World J Gastroenterol 2005;11:6360)
 Eye: Fuchs endothelial dystrophy (Cornea 2006;25:956)
 Liver: bile duct adenoma, mesenchymal hamartoma, chronic allograft rejection (Am J Clin Pathol 2011;135:238). perivenular hepatocytes associated with cholestatic chemistry profile and heart failure (Mod Pathol 2010;23:1650)
 Lymph nodes: individual / clusters of neuroendocrine cells (Am J Surg Pathol 2010;34:1701)
 Nephrogenic adenoma of GU tract (Am J Surg Pathol 2009;33:1654)
 Pancreas: lymphoepithelial cyst (Mod Pathol 2010;23:1467)
 Salivary gland oncocytoma (Laryngoscope 2005;115:1097)

CK7 expression in malignant tumors

 CK7 expression in tumors

• cutaneous Paget disease (#9500217#, #9331290#)
  • Intraepidermal cytokeratin 7 expression is not restricted to Paget cells but is also seen in Toker cells and Merkel cells. (#9989849#)

 mucinous cystadenocarcinoma of the breast

• All cases stain positively with cytokeratin 7 (CK7) but were negative with cytokeratin 20 (CK20).

 papilary renal cell carcinoma
 benign proliferative nipple duct lesions (#10555003#)
 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.

 mucinous adenocarcinomas from

• ampulla
• biliary tree
• esophagus
• pancreas
• stomach (93%, Am J Surg Pathol 2011;35:1830)
• colon / rectum / anus (only 19% are CK7+, most from rectum/anus, Am J Surg Pathol 2011;35:1830)

 Anal duct carcinoma (Hum Pathol 2011 Aug 3 [Epub ahead of print])
 Appendiceal epithelial neoplasms (benign and malignant-33%, Hum Pathol 2005;36:1217)
 Basaloid squamous cell carcinoma of Waldeyer’s ring (Hum Pathol 2000;31:1096)
 Bile duct carcinoma (90%, Hum Pathol 2005;36:1226)
 Bladder adenocarcinoma (63%, Appl Immunohistochem Mol Morphol 2005;13:358)
 Breast carcinoma (Ann Diagn Pathol 1999;3:350)
 Carcinoid (GI, 11%, Hum Pathol 2001;32:1087)
 Cervical adenocarcinoma (Am J Clin Pathol 2009;132:531)
 Colon adenocarcinoma related to ulcerative colitis (59%, Virchows Arch 2006;448:756)
 Germ cell tumors at various sites (variable, but usually negative)
 Kidney

• renal cell carcinoma
  • chromophobe (Am J Clin Pathol 2007;127:225)
  • clear cell tubulopapillary (Am J Surg Pathol 2010;34:1608)
  • collecting duct, papillary (Am J Surg Pathol 2011;35:949)

 Liver: hepatocellular carcinoma (10-34% positive, Mod Pathol 2006;19:460)

• particularly scirrhous / fibrolamellar type (Histopathology 2005;47:382) or age 30 or younger, Am J Clin Pathol 2005;124:512)

 Lung

• adenocarcinoma-94% vs. squamous cell-60% (Hum Pathol 2006;37:542, Am J Surg Pathol 2011;35:15)

 Merkel cell (50%, J Eur Acad Dermatol Venereol 2005;19:546)
 Mesothelioma, including with rhabdoid features (Mod Pathol 2006;19:373)

 Ovarian carcinoma (Mod Pathol 2006;19:1421)

• but mucinous carcinoma with pseudomyxoma ovarii (suggesting teratomatous derivation) are CK7- (Am J Surg Pathol 2007;31:854);
• ovarian carcinoids (24%)
• Sertoli cell tumors (13%, Am J Surg Pathol 2007;31:255)

 Paget’s cells (breast, anal, vulvar, esophageal, but not vulvar secondary to anorectal carcinoma, Am J Surg Pathol 1998;22:170-perianal, Hum Pathol 2002;33:545-vulvar, Am J Surg Pathol 2008;32:1068-esphageal)
 Pancreatic carcinoma including intestinal type (Ann Diagn Pathol 2007;11:3)
 Pseudomyxoma peritonei (almost all cases have variable positivity, Histopathology 2006;49:381)
 Salivary gland: carcinoma (100%, Pathol Int 2005;55:386), lymphadenoma (Mod Pathol 2011 Sep 2 [Epub ahead of print])
 Sinonasal adenocarcinoma (most, Ann Otol Rhinol Laryngol 2006;115:59)
 Small intestinal adenocarcinoma (Am J Surg Pathol 2004;28:1499)
 Synovial sarcoma (many, Mod Pathol 2006;19:659)
 Urothelial carcinoma (87%), urothelial carcinoma in situ of the bladder with glandular differentiation (Hum Pathol 2011;42:1653)
 Uterus: endometrioid adenocarcinoma (100%), endocervical (50%, Int J Gynecol Pathol 2012;31:57); most mucinous tumors (Appl Immunohistochem Mol Morphol 2009;17:8)

Negative for CK7 detection

 Adrenocortical carcinoma
 Cervical squamous epithelium
 Endometrial stromal sarcoma (Hum Pathol 2008;39:1459)
 GI epithelium (normal)
 GI carcinomas-nonmucinous (but see exceptions above)
 Hepatocytes; hepatoid adenocarcinoma
 Kidney

• normal tubules
• carcinoid (may have focal staining) (Am J Surg Pathol 2007;31:1539)
• clear cell carcinoma (usually)
• oncocytoma

 Nasal cavity: nonkeratinizing nasopharyngeal carcinoma-differentiated and undifferentiated

 Pituitary adenomas (usually, Endocr Pathol 2005;16:201)
 Prostate adenocarcinoma (Mod Pathol 2000;13:962), but prostatic mucin producing urothelial-type carcinoma is usually CK7+ (83%, Am J Surg Pathol 2007;31:1323)
 Skin (squamous epithelium)
 Tongue
 Yolk sac tumor (Am J Surg Pathol 2004;28:1499)

CK7 /CK20 coupled immunochemistry

 CK7+ / CK20+ tumors

• carcinomas of bile duct (extrahepatic / gallbladder, often, Pathol Res Pract 2003;199:65)
• lung-mucinous bronchioloalveolar (Am J Clin Pathol 2004;122:421)
• pancreas (Cancer 2006;106:693, but see Arch Pathol Lab Med 2000;124:1196)
• urothelium (often, Arch Pathol Lab Med 2001;125:921, Hum Pathol 2002;33:1136)
• primary mucinous tumors of ovary (74%)
• upper GI tract (78%)
• endocervix (88%, Am J Surg Pathol 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, Am J Surg Pathol 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 Pathol 2005;36:275)
• primary mucinous tumors of lower GI tract (79%, Am J Surg Pathol 2006;30:1130)
• primary bladder adenocarcinoma (29%, Am J Surg Pathol 2001;25:1380)

 CK7- / CK20-

• carcinoma of adrenal cortex
• prostate (Mod Pathol 2000;13:962)

CK7 use in differential diagnostic

 To distinguish primary lung carcinoma (CK7+ / CK20-) from metastatic colonic carcinoma to lung (CK7- / CK20+, BMC Cancer 2006;6:31) with the CDX2 labelling
 To distinguish adenocarcinoma of distal esophagus (CK7+ / CK19+: 90%, CK7+ / CK20-: 74%) from proximal stomach adenocarcinoma (CK7+ / CK19+: 44%, CK7+ / CK20-: 24%, Am J Surg Pathol 2002;26:1213)
 To distinguish chromophobe carcinoma (diffuse CK7+ staining) from oncocytoma (usually CK7-, Anal Quant Cytol Histol 2006;28:228)
 To help distinguish papillary renal cell carcinoma (CK7+) from metanephric adenoma (CK7-, Mod Pathol 2006;19:218)
 To distinguish endometrioid and clear cell carcinoma (CK7+) from yolk sac tumors (CK7-, Am J Surg Pathol 2004;28:1499)

See also

 KRT19 (CK19)

References

 http://www.pathologyoutlines.com/topic/stainsck7.html

Breast cancer and mammary lesions

 Benign proliferative nipple duct lesions frequently contain CAM 5.2 and anti-cytokeratin 7 immunoreactive cells in the overlying epidermis. Zeng Z, Melamed J, Symmans PJ, Cangiarella JF, Shapiro RL, Peralta H, Symmans WF. Am J Surg Pathol. 1999 Nov;23(11):1349-55. PMID: #10555003#

 Mucinous cystadenocarcinoma of the breast. Koenig C, Tavassoli FA. Am J Surg Pathol. 1998 Jun;22(6):698-703. PMID: #9630176#

Paget disease

 Intraepidermal cytokeratin 7 expression is not restricted to Paget cells but is also seen in Toker cells and Merkel cells. Lundquist K, Kohler S, Rouse RV. Am J Surg Pathol. 1999 Feb;23(2):212-9. PMID: #9989849#

 Perianal Paget’s disease: a histologic and immunohistochemical study of 11 cases with and without associated rectal adenocarcinoma. Goldblum JR, Hart WR. Am J Surg Pathol. 1998 Feb;22(2):170-9. PMID: #9500217#

 Vulvar Paget’s disease: a clinicopathologic and immunohistochemical study of 19 cases. Goldblum JR, Hart WR. Am J Surg Pathol. 1997 Oct;21(10):1178-87. PMID: #9331290#

Renal cell carcinomas

 Renal cell carcinomas in children and young adults: increased incidence of papillary architecture and unique subtypes. Renshaw AA, Granter SR, Fletcher JA, Kozakewich HP, Corless CL, Perez-Atayde AR. Am J Surg Pathol. 1999 Jul;23(7):795-802. PMID: #10403302#