• Type II keratin of simple nonkeratinizing epithelia; molecular weight 51.4 kDa (OMIM: Keratin 7, TYPE II; KRT7 [Accessed 14 September 2020])
• Expression similar to but more limited than keratins 8 and 18 in simple, pseudostratified and ductal epithelium, mesothelium and urothelium

• Also known as keratin 7, CK7, KRT 7, K7

• Like other keratins, component of intermediate filaments forming cytoskeleton of epithelial cells (J Anat 2009;214:516)
• Type II keratins, arranged in pairs of heterotypic keratin chains, are expressed during differentiation of certain epithelial tissues (NCBI - Gene - KRT7)

• CK7 expression in esophageal squamous cell carcinoma is an independent prognostic factor for poor overall survival (Neoplasma 2018;65:469)
• CK7 / CK19 index is an independent adverse prognostic factor for postoperative survival in intrahepatic cholangiocarcinoma patients (J Surg Oncol 2018;117:1531)
• No association with prognosis when used as a marker for intestinal versus pancreaticobiliaryorigin in ampullary carcinoma (Am J Surg Pathol 2017;41:865)
• Expression in cervical low grade squamous intraepithelial lesion (LSIL / CIN 1) associated with higher rates of subsequent HSIL but clinical utility potentially limited by low magnitude of risk difference and interpretive variability; no prognostic utility in CIN 2 (Am J Surg Pathol 2013;37:1311, Am J Surg Pathol 2017;41:143, Am J Surg Pathol 2018;42:479)
• Colorectal tumor cells expressing CK7 may demonstrate invasive capability with metastatic potential (J Cancer 2019;10:2510)
• High CK7 expression in BRAF-V600E mutated metastatic colorectal cancer confers worse overall survival (Br J Cancer 2019;121:593)

Contributed by Kruti P. Maniar, M.D.



Contributed by Andrey Bychkov, M.D., Ph.D., Eddie Fridman, M.D. (Case #194) and Leica Microsystems


Contributed by Maria Tretiakova, M.D., Ph.D.

• Anal duct carcinoma (Hum Pathol 2012;43:216)
• Appendiceal mucinous neoplasms, subset (31%) (Histopathology 2016;68:977)
• Basaloid squamous cell carcinoma of Waldeyer ring (Hum Pathol 2000;31:1096)
• Bile duct carcinoma (Pathol Res Pract 2003;199:65)
• Bladder adenocarcinoma (63%) (Appl Immunohistochem Mol Morphol 2005;13:358)
• Breast carcinoma (Ann Diagn Pathol 1999;3:350)
• Cervical adenocarcinoma (HPV related and gastric type) and squamous cell carcinoma (Mod Pathol 2000;13:962, Am J Clin Pathol 2009;132:531, Am J Surg Pathol 2016;40:636)
• Colon adenocarcinoma, small subset including those related to ulcerative colitis (59%) and some rectal adenocarcinoma; also see above as CK7 expression relates to prognostication of some colorectal adenocarcinomas (Am J Surg Pathol 2011;35:1830, Virchows Arch 2006;448:756)
• Endometrial adenocarcinoma (Int J Gynecol Pathol 2002;21:4)
• Esophageal adenocarcinoma (Am J Surg Pathol 2002;26:1213)
• Gastric adenocarcinoma (71%) (Hum Pathol 2004;35:576)
• Hepatocellular carcinoma, subset (10 - 34%), particularly scirrhous and fibrolamellar types and those in patients ≤ 30 years (Am J Clin Pathol 2005;124:512, Histopathology 2005;47:382, Int J Surg Pathol 2010;18:313, Mod Pathol 2006;19:460)
• Lung: adenocarcinoma and primary pulmonary mucoepidermoid carcinoma (PLoS One 2015;10:e0143169, Hum Pathol 2006;37:542)
• Merkel cell carcinoma, subset (23%); it is also noted that CK7-/CK20- negative Merkel cell carcinomas have been described (Appl Immunohistochem Mol Morphol 2000;8:310, Am J Dermatopathol 2017;39:208)
• Mesothelioma, pleural and peritoneal (Cancer. 2001;92:2727, Arch Pathol Lab Med 2018;142:236)
• Ovarian endometrioid, clear cell, serous and seromucinous carcinoma and most primary mucinous carcinoma (74%) (Am J Surg Pathol 2006;30:1130, Am J Surg Pathol 2015;39:983, Am J Surg Pathol 2004;28:1499)
• Ovarian carcinoid, subset (24%); Sertoli cell tumors, small subset (13%) (Am J Surg Pathol 2007;31:255)
• Paget disease, mammary and extramammary (breast, anal, vulvar and esophageal), except vulvar secondary to anorectal carcinoma (Am J Surg Pathol 1998;22:170, Hum Pathol 2002;33:545, Am J Surg Pathol 2008;32:1068)
• Pancreatic adenocarcinoma, including intestinal type (Ann Diagn Pathol 2007;11:3, Arch Pathol Lab Med 2000;124:1196)
• Renal cell carcinoma (chromophobe, papillary, clear cell papillary, collecting duct types) (Arch Pathol Lab Med 2012;136:410)
• Salivary gland carcinoma (Mod Pathol 2004;17:407)
• Sebaceous carcinoma (Am J Dermatopathol 2015;37:809)
• Sinonasal adenocarcinoma, including subset of SMARCB1 (INI-1) deficient sinonasal carcinoma (48%) (Am J Surg Pathol 2017;41:458, Ann Otol Rhinol Laryngol 2006;115:59, Head Neck Pathol 2016;10:68)
• Small intestinal adenocarcinoma (Am J Surg Pathol 2004;28:1352)
• SMARCA4 deficient pulmonary adenocarcinoma (CK7 +, TTF-1 -, HepPar1 +) (Virchows Arch 2017;471:599)
• Synovial sarcoma (many) (Mod Pathol 2006;19:659)
• Thyroid carcinoma (Appl Immunohistochem Mol Morphol 2000;8:189)
• Urothelial carcinoma (Arch Pathol Lab Med 2001;125:921, Hum Pathol 2002;33:1136)
• Yolk sac tumors of somatic derivation, tumors of germ cell derivation usually negative) (Histopathology 2016;69:739)

A 54 year old woman presents with a 10 cm right ovarian mass. Histology demonstrates a mucinous carcinoma and the tumor cells are negative for CK7 and positive for CK20. Which of the following tumors is most likely to demonstrate this immunohistochemical profile?

1. Metastatic breast adenocarcinoma
2. Metastatic cervical adenocarcinoma
3. Metastatic colonic adenocarcinoma
4. Metastatic gastric adenocarcinoma
5. Primary ovarian mucinous carcinoma

C. Adenocarcinoma of the colon is most often CK7- / CK20+. Breast carcinoma is usually CK7+ / CK20-, cervical adenocarcinoma is usually CK7+ / CK20-, gastric carcinoma can be either CK7+ / CK20- (majority) or CK7+ / CK20+ and primary ovarian mucinous carcinoma is either CK7+ / CK20+ or CK7+ / CK20 variable (although lower GI type mucinous tumors arising in teratoma can be CK7-).

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Reference: Cytokeratin 7 (CK7, K7)

Which of the following is the best immunohistochemical marker for the diagnosis of primary, extramammary Paget disease?

1. CK7
2. CK20
3. p63
4. SOX10
5. Uroplakin

A. Of the above, CK7 is the best screening marker for primary, extramammary Paget disease. Sox10 would be positive in a melanocytic lesion (i.e. melanoma in situ), p63 positive in squamous cell carcinomas or primary adnexal neoplasms and uroplakin is positive in pagetoid urothelial intraepithelial neoplasia (PUIN). CK20 could be expressed in either metastatic colorectal adenocarcinoma or intraepidermal Merkel cell carcinoma (demonstrating perinuclear dot-like positivity).

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Reference: Cytokeratin 7 (CK7, K7)

Which staining pattern would most likely be appreciated in chromophobe renal cell carcinoma?

1. CK7-/c-Kit-/Hale’s Colloidal Iron-
2. CK7+/c-Kit-/Hale’s Colloidal Iron-
3. CK7+/c-Kit+/Hale’s Colloidal Iron-
4. CK7+/c-Kit+/Hale’s Colloidal Iron+

D. Classically, chromophobe renal cell carcinoma would be positive for CK7, c-Kit (or CD117) and Hale’s colloidal iron. Oncocytoma may demonstrate scattered CK7 positivity while conventional clear cell RCC is usually CK7 negative. Additionally, chromophobe RCC can stain diffusely for Hale’s colloidal iron while oncocytoma may show apical, non-diffuse staining. It must also be noted that, despite the above immunohistochemical studies, the distinction between different oncocytic / eosinophilic neoplasms can often be challenging as many of the entities may demonstrate significant morphologic overlap.

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Reference: Cytokeratin 7 (CK7, K7)