Cytokeratins 7 and 20 in Primary and Secondary Mucinous Tumors of the Ovary: Analysis of Coordinate Immunohistochemical Expression Profiles and Staining Distribution in 179 Cases

Abstract

Coordinate expression profiles for cytokeratins 7 and 20 (CK7 and CK20) are useful for distinguishing certain types of adenocarcinomas but use for distinction of primary and secondary mucinous tumors in the ovary is limited due to the existence of a number of tumor types exhibiting overlapping CK7/CK20 immunoprofiles; the use of staining distribution patterns in the distinction of tumors with shared profiles has not been evaluated in detail. We report analysis of both coordinate expression profiles and staining distribution in 179 rigorously classified mucinous tumors in the ovary, including 53 primary tumors [35 atypical proliferative (borderline) mucinous tumors of gastrointestinal type and 18 invasive mucinous carcinomas] and 126 secondary tumors [28 colorectal adenocarcinomas, 54 appendiceal tumors (23 adenocarcinomas, 31 low-grade adenomatous mucinous tumors associated with pseudomyxoma peritonei), 14 pancreatic adenocarcinomas, 8 endocervical adenocarcinomas, 5 gastric adenocarcinomas, 4 gallbladder/biliary tract adenocarcinomas, and 13 adenocarcinomas of unknown primary sites). A CK7+/CK20+ immunoprofile was the most common profile in primary ovarian tumors (74%), upper gastrointestinal tract tumors (78%), and endocervical tumors (88%) but was occasionally observed in lower intestinal tract tumors (colorectal: 11%; appendiceal: 13% of low-grade tumors, 35% of carcinomas). A CK7-/CK20+ immunoprofile was the most common profile in lower intestinal tract tumors (79%) and was uncommon in upper gastrointestinal tract tumors (9%), rarely seen in primary ovarian tumors (4%), and not seen in endocervical tumors. A CK7+/CK20- profile was observed in some primary ovarian (23%), upper gastrointestinal tract (13%), and endocervical tumors (13%) but not in lower intestinal tract tumors. For CK7+ tumors, staining distribution was very frequently diffuse (>50% of tumors cells positive) in primary ovarian, upper gastrointestinal tract, and endocervical tumors, whereas staining distribution was often focal (<50% of tumors cells positive) when present in colorectal and appendiceal carcinomas but not in low-grade appendiceal tumors. For CK20+ tumors, staining distribution was variable but often focal in primary ovarian tumors and nonlower intestinal tract tumors, whereas the pattern was almost always diffuse in lower intestinal tract tumors. Immunohistochemical staining distribution can supplement CK7/CK20 coordinate expression profiles to distinguish subsets of primary ovarian and metastatic lower intestinal tract mucinous tumors having overlapping immunoprofiles but neither coordinate expression profiles nor staining distribution distinguishes primary ovarian tumors from the nonlower intestinal tract metastases.

Data set for reporting of ovary, fallopian tube and primary peritoneal carcinoma: recommendations from the International Collaboration on Cancer Reporting (ICCR)

“…Thus CK7 immunopositivity is typically of greater extent than CK20 immunopositivity in primary ovarian mucinous tumours and CK20 staining is more extensive than CK7 in metastatic colonic adenocarcinoma. 133 Metastatic pancreatic or biliary adenocarcinoma may mimic a primary ovarian mucinous neoplasm of intestinal type, either borderline or malignant, and immunohistochemistry is of limited value. Most commonly, these tumour types are diffusely positive with CK7 while CK20 is variable, being negative, focally or diffusely positive.…”

Distinguishing primary from secondary mucinous ovarian tumors: an algorithm using the novel marker DPEP1

“…8,9,22 To evaluate the accuracy that the positivity of each marker predicts primary mucinous ovarian cancer vs ovarian metastasis of digestive organ cancer, we calculated the cutoff value by ROC curve. Each cutoff value of CK7, CK20, CDX2, and DPEP1 classified our cases in the accuracy of 76, 64, 83, and 81%, respectively (Supplementary Figure 1).…”

“…Contrary to the case of colorectal cancers, it is known that CK7, CK20, and CDX2 are not useful as markers to distinguish primary mucinous ovarian carcinomas from ovarian metastases of non-colorectal digestive organ cancers. 8,22 However, few reports have tested their utility in combination. Therefore, we conducted an analysis by combining multiple immunohistochemical markers.…”

Differential diagnostic and functional role of the multi-marker phenotype CDX2/CK20/CK7 in colorectal cancer stratified by mismatch repair status

“…2,5 According to several studies the multi-marker phenotype CK20 þ /CK7À is observed in colorectal cancer in approximately 75-95% 2,14 of cases whereas the multimarker phenotype CK20À/CK7 þ favors primary tumors of the lung, breast, biliary tract, pancreas, ovary and endometrium. 5 However, the combined use of CK20 and CK7 is limited, especially in the distinction of primary and secondary mucinous tumors in the ovary 16 thereby making the addition of other markers mandatory.…”