Stains & molecular markers
Cytokeratin 7 (CK7, K7)


Topic Completed: 17 September 2020

Minor changes: 17 September 2020

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PubMed Search: CK7 stain "loattrfree full text"[sb]

Kruti P. Maniar, M.D.
Brandon Umphress, M.D.
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Cite this page: Maniar KP, Umphress B. Cytokeratin 7 (CK7, K7). PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/stainsck7.html. Accessed September 29th, 2020.
Definition / general
Essential features
  • Membranous / cytoplasmic marker with expression in many normal epithelia and epithelial tumors
  • Despite wide distribution, useful as part of a panel in determining primary site of metastatic carcinoma
  • Generally expressed (with some variation) in adenocarcinoma of lung, breast, thyroid, endometrium, cervix, ovary, salivary gland, upper GI tract, urothelial carcinoma, papillary renal cell carcinoma and Paget disease
  • Generally negative (with some variation) in colorectal carcinoma, Merkel cell carcinoma, hepatocellular carcinoma, prostatic adenocarcinoma, adrenocortical tumors and squamous cell carcinoma
Terminology
  • Also known as keratin 7, CK7, KRT 7, K7
Pathophysiology
  • 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)
Uses by pathologists
Prognostic factors
  • 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)
Interpretation
  • Membranous / cytoplasmic staining, ranging from weak / focal to strong / diffuse
Microscopic (histologic) images

Contributed by Kruti P. Maniar, M.D., Andrey Bychkov, M.D., Ph.D., Eddie Fridman, M.D., Maria Tretiakova, M.D., Ph.D. and Leica Microsystems

Cervical squamocolumnar junction

Cholangio- carcinoma

Colon

Liver portal tract

Lung adenocarcinoma


Ovarian seromucinous borderline tumor

Pancreas

Yolk sac tumor, glandular variant

Ovarian cancer

Urothelial carcinoma


Urethra: clear cell adenocarcinoma

Ureter (normal)

Normal kidney

Normal kidney

Clear cell RCC

Clear cell RCC

Clear cell papillary RCC

Clear cell papillary RCC


Papillary RCC, type1

Papillary RCC, type1

Papillary RCC, type 2

Papillary RCC, type 2

Chromophobe RCC

Chromophobe RCC

Oncocytoma

Oncocytoma

Positive staining - malignant
Negative staining - normal
Negative staining - tumor / disease
Sample pathology report
  • Skin, shoulder, biopsy:
    • Metastatic adenocarcinoma, consistent with breast origin (see comment)
    • Comment: Immunohistochemical staining demonstrates diffuse tumor positivity for CK7, GATA3, ER and PR and negativity for CK20, TTF-1, WT-1 and Pax-8. The morphologic and immunophenotypic findings are consistent with metastatic breast adenocarcinoma. Clinical correlation is recommended.
  • Vulva, biopsy:
    • Intraepidermal adenocarcinoma, consistent with Paget disease (see comment)
    • Comment: Histologic sections demonstrate atypical epithelioid cells with prominent nucleoli and clear-to-pale cytoplasm exhibiting intraepidermal growth in a pagetoid-like fashion. No dermal invasion is identified. Immunohistochemical studies show the cells to be positive for CK7, CAM5.2 and HER2 while negative for SOX10, p63, CK5/6, CK20 and adipophilin. The morphologic and immunophenotypic findings are consistent with primary Paget disease of the vulva. Clinical correlation is recommended to exclude metastasis from an extracutaneous site.
Board review style question #1
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
Board review answer #1
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)
Board review style question #2
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
Board review answer #2
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)
Board review style question #3
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+
Board review answer #3
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)
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