The cytokeratin 17 expression in primary ovarian tumors has diagnostic but not prognostic significance
Language English Country Germany Media print-electronic
Document type Journal Article
Grant support
AZV NV19-03-00007
Ministerstvo Zdravotnictví Ceské Republiky
MH CZ DRO-VFN 64165
Ministerstvo Zdravotnictví Ceské Republiky
UNCE204065
Univerzita Karlova v Praze
EF16_013/0001674
European Regional Development Fund
BBMRI_CZ LM2018125
European Regional Development Fund
PubMed
35554675
DOI
10.1007/s00428-022-03338-z
PII: 10.1007/s00428-022-03338-z
Knihovny.cz E-resources
- Keywords
- Cytokeratin 17, Differential diagnosis, Gastrointestinal tract tumors, Ovarian tumors,
- MeSH
- Adenocarcinoma * diagnosis MeSH
- Diagnosis, Differential MeSH
- Gastrointestinal Neoplasms * diagnosis MeSH
- Immunohistochemistry MeSH
- Keratin-17 MeSH
- Colorectal Neoplasms * diagnosis MeSH
- Humans MeSH
- Biomarkers, Tumor analysis MeSH
- Pancreatic Neoplasms * diagnosis MeSH
- Ovarian Neoplasms * pathology MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Keratin-17 MeSH
- Biomarkers, Tumor MeSH
We assessed the value of cytokeratin 17 (CK17) expression for the differential diagnosis between primary ovarian mucinous tumors and metastases from the gastrointestinal tract (GIT) and the significance of CK17 expression in a broad spectrum of primary ovarian tumors with respect to their prognosis. The sample set consisted of 554 primary ovarian tumors and 255 GIT tumors. In the primary ovarian tumors, a higher CK17 expression (in > 10% of tumors cells) was present only in 0-11.4% of all tumors (including mucinous tumors, micropapillary serous borderline tumors, clear cell, endometrioid, and high-grade serous carcinomas). The only exception was low-grade serous carcinoma, where higher CK17 expression was present in 24% of cases. Concerning GIT tumors, the higher levels of CK 17 expression (in > 10% of tumor cells) were observed in the upper GIT tumors (68.5% of pancreatic ductal adenocarcinoma, 61.6% of gallbladder adenocarcinoma, and 46% of gastric adenocarcinoma), which differs substantially not only from most of the primary ovarian tumors, but also from colorectal carcinoma (3.7%; p < 0.001). The results of our study suggest that expression of CK17 can potentially be used as an adjunct marker in differential diagnosis between primary ovarian mucinous tumors and metastases from the upper GIT, but not from colorectal carcinoma. However, in GIT tumors, CK17 can be used in the differential diagnosis between adenocarcinomas of the upper and lower GIT. Statistical analysis did not reveal strong association of CK17 expression with clinicopathological variables or patient outcomes in any primary ovarian tumors.
Department of Oncological Pathology Masaryk Memorial Cancer Institute Brno Czech Republic
Department of Pathology Belfast Health and Social Care Trust Belfast UK
Department of Pathology Faculty of Medicine University of Debrecen 4032 Debrecen Hungary
Department of Pathology General Hospital Graz 2 Graz Austria
Department of Pathology Leiden University Medical Center Leiden Netherlands
Department of Pathology University of California San Diego San Diego CA USA
See more in PubMed
Moll R, Divo M, Langbein L (2008) The human keratins: biology and pathology. Histochem Cell Biol 129(6):705–733 PubMed DOI PMC
Troyanovsky SM et al (1989) Patterns of expression of keratin 17 in human epithelia: dependency on cell position. J Cell Sci 93(Pt 3):419–426 PubMed DOI
Guelstein VI et al (1988) Monoclonal antibody mapping of keratins 8 and 17 and of vimentin in normal human mammary gland, benign tumors, dysplasias and breast cancer. Int J Cancer 42(2):147–153 PubMed DOI
Miettinen M et al (1997) Keratin 17: immunohistochemical mapping of its distribution in human epithelial tumors and its potential applications. Applied Immunohistochemistry 5(3):152–159 DOI
Guelstein VI et al (1993) Immunohistochemical localization of cytokeratin 17 in transitional cell carcinomas of the human urinary tract. Virchows Arch B Cell Pathol Incl Mol Pathol 64(1):1–5 PubMed DOI
Escobar-Hoyos LF et al (2014) Keratin 17 in premalignant and malignant squamous lesions of the cervix: proteomic discovery and immunohistochemical validation as a diagnostic and prognostic biomarker. Mod Pathol 27(4):621–630 PubMed DOI
Maddox P et al (1999) Differential expression of keratins 10, 17, and 19 in normal cervical epithelium, cervical intraepithelial neoplasia, and cervical carcinoma. J Clin Pathol 52(1):41–46 PubMed DOI PMC
Regauer S, Reich O (2007) CK17 and p16 expression patterns distinguish (atypical) immature squamous metaplasia from high-grade cervical intraepithelial neoplasia (CIN III). Histopathology 50(5):629–635 PubMed DOI PMC
Podoll MB et al (2017) Assessment of CK17 as a marker for the diagnosis of differentiated vulvar intraepithelial neoplasia. Int J Gynecol Pathol 36(3):273–280 PubMed DOI
Escobar-Hoyos LF et al (2015) Keratin-17 promotes p27KIP1 nuclear export and degradation and offers potential prognostic utility. Cancer Res 75(17):3650–3662 PubMed DOI
Goldstein NS, Bassi D, Uzieblo A (2001) WT1 is an integral component of an antibody panel to distinguish pancreaticobiliary and some ovarian epithelial neoplasms. Am J Clin Pathol 116(2):246–252 PubMed DOI
Ackroyd SA et al (2019) Pancreaticobiliary metastasis presenting as primary mucinous ovarian neoplasm: a systematic literature review. Gynecol Oncol Rep 28:109–115 PubMed DOI PMC
Nemejcova K et al (2021) A comprehensive analysis of the expression, epigenetic and genetic changes of HNF1B and ECI2 in 122 cases of high-grade serous ovarian carcinoma. Oncol Lett 21(3):185 PubMed DOI PMC
Bartu M et al (2020) Expression, epigenetic, and genetic changes of HNF1B in colorectal lesions: an analysis of 145 cases. Pathol Oncol Res 26(4):2337–2350 PubMed DOI
Dundr P et al (2021) Uterine cellular leiomyomas are characterized by common HMGA2 aberrations, followed by chromosome 1p deletion and MED12 mutation: morphological, molecular, and immunohistochemical study of 52 cases. Virchows Arch 480(2):281–289 PubMed DOI
Yang HS et al (2012) Clinical significance of MUC1, MUC2 and CK17 expression patterns for diagnosis of pancreatobiliary arcinoma. Biotech Histochem 87(2):126–132 PubMed DOI
Roa-Pena L et al (2019) Keratin 17 identifies the most lethal molecular subtype of pancreatic cancer. Sci Rep 9(1):11239 PubMed DOI PMC
Ide M et al (2012) Keratin 17 expression correlates with tumor progression and poor prognosis in gastric adenocarcinoma. Ann Surg Oncol 19(11):3506–3514 PubMed DOI
Lok T et al (2014) Immunohistochemical distinction between intrahepatic cholangiocarcinoma and pancreatic ductal adenocarcinoma. Hum Pathol 45(2):394–400 PubMed DOI
Kim K et al (2017) Cytokeratin 17 expression is associated with poor prognosis in gallbladder adenocarcinoma. Appl Immunohistochem Mol Morphol 25(5):346–350 PubMed DOI
Ujiie D et al (2020) KRT17 as a prognostic biomarker for stage II colorectal cancer. Carcinogenesis 41(5):591–599 PubMed DOI
Wang YF et al (2013) Overexpression of keratin 17 is associated with poor prognosis in epithelial ovarian cancer. Tumour Biol 34(3):1685–1689 PubMed DOI
Carrasco C et al (2021) The evaluation of 17 gastrointestinal tumor markers reveals prognosis value for MUC6, CK17, and CD10 in gallbladder-cancer patients. Diagnostics (Basel) 11(2):153 DOI
Chu PG et al (2005) Immunohistochemical staining in the diagnosis of pancreatobiliary and ampulla of Vater adenocarcinoma: application of CDX2, CK17, MUC1, and MUC2. Am J Surg Pathol 29(3):359–367 PubMed DOI
Hamada T et al (2008) Immunohistochemical analysis of reserve cell-like cells of ovarian mullerian mucinous/mixed epithelial borderline tumor. Int J Gynecol Pathol 27(2):199–206 PubMed
Sarbia M et al (2007) Differentiation between pancreaticobiliary and upper gastrointestinal adenocarcinomas: is analysis of cytokeratin 17 expression helpful? Am J Clin Pathol 128(2):255–259 PubMed DOI
Kim CY et al (2012) Proteomic analysis reveals overexpression of moesin and cytokeratin 17 proteins in colorectal carcinoma. Oncol Rep 27(3):608–620 PubMed
Mockler D et al (2017) Keratin 17 is a prognostic biomarker in endocervical glandular neoplasia. Am J Clin Pathol 148(3):264–273 PubMed DOI
Merkin RD et al (2017) Keratin 17 is overexpressed and predicts poor survival in estrogen receptor-negative/human epidermal growth factor receptor-2-negative breast cancer. Hum Pathol 62:23–32 PubMed DOI
Regenbogen E et al (2018) Elevated expression of keratin 17 in oropharyngeal squamous cell carcinoma is associated with decreased survival. Head Neck 40(8):1788–1798 PubMed
Zeng Y et al (2020) Keratin 17 suppresses cell proliferation and epithelial-mesenchymal transition in pancreatic cancer. Front Med (Lausanne) 7:572494 DOI
Bai JDK et al (2019) Keratin 17 is a negative prognostic biomarker in high-grade endometrial carcinomas. Hum Pathol 94:40–50 PubMed DOI
Li C et al (2021) A pan-cancer analysis of the oncogenic role of keratin 17 (KRT17) in human tumors. Transl Cancer Res 10(10):4489–4501 PubMed DOI PMC
Pan CH et al (2020) An unbiased high-throughput drug screen reveals a potential therapeutic vulnerability in the most lethal molecular subtype of pancreatic cancer. Mol Oncol 14(8):1800–1816 PubMed DOI PMC
Seidman JD, Kurman RJ, Ronnett BM (2003) Primary and metastatic mucinous adenocarcinomas in the ovaries: incidence in routine practice with a new approach to improve intraoperative diagnosis. Am J Surg Pathol 27(7):985–993 PubMed DOI
Platz CE, Benda JA (1995) Female genital tract cancer. Cancer 75(1 Suppl):270–294 PubMed DOI
Mink PJ, Sherman ME, Devesa SS (2002) Incidence patterns of invasive and borderline ovarian tumors among white women and black women in the United States. Results from the SEER Program, 1978-1998. Cancer 95(11):2380–9 PubMed DOI
Dundr P et al (2021) Primary mucinous ovarian tumors vs ovarian metastases from gastrointestinal tract, pancreas and biliary tree: a review of current problematics. Diagn Pathol 16(1):20 PubMed DOI PMC
McCluggage WG, Wilkinson N (2005) Metastatic neoplasms involving the ovary: a review with an emphasis on morphological and immunohistochemical features. Histopathology 47(3):231–247 PubMed DOI
McCluggage WG, Young RH (2005) Immunohistochemistry as a diagnostic aid in the evaluation of ovarian tumors. Semin Diagn Pathol 22(1):3–32 PubMed DOI
McCluggage WG (2012) Immunohistochemistry in the distinction between primary and metastatic ovarian mucinous neoplasms. J Clin Pathol 65(7):596–600 PubMed DOI
Hu J et al (2018) The pathologic distinction of primary and metastatic mucinous tumors involving the ovary: a re-evaluation of algorithms based on gross features. Ann Diagn Pathol 37:1–6 PubMed DOI
Talia KL, Parra-Herran C, McCluggage WG (2022) Ovarian mucinous and seromucinous neoplasms: problematic aspects and modern diagnostic approach. Histopathology 80(2):255–278 PubMed DOI
Meagher NS et al (2019) A combination of the immunohistochemical markers CK7 and SATB2 is highly sensitive and specific for distinguishing primary ovarian mucinous tumors from colorectal and appendiceal metastases. Mod Pathol 32(12):1834–1846 PubMed DOI PMC
Park CK, Kim HS (2018) Clinicopathological characteristics of ovarian metastasis from colorectal and pancreatobiliary carcinomas mimicking primary ovarian mucinous tumor. Anticancer Res 38(9):5465–5473 PubMed DOI
Meriden Z et al (2011) Ovarian metastases of pancreaticobiliary tract adenocarcinomas: analysis of 35 cases, with emphasis on the ability of metastases to simulate primary ovarian mucinous tumors. Am J Surg Pathol 35(2):276–288 PubMed DOI
Yoshida H et al (2021) Gross mucinous multinodular appearance aids in the identification of ovarian metastases in low-grade appendiceal mucinous neoplasms during intraoperative consultation. Ann Diagn Pathol 50:151641 PubMed DOI
Young RH, Hart WR (1989) Metastases from carcinomas of the pancreas simulating primary mucinous tumors of the ovary. A report of seven cases. Am J Surg Pathol 13(9):748–56 PubMed DOI
Alghamdi S, Alghaashamy K, Pinto A (2020) Expression of SMAD4 is retained in most gynecologic tumors with mucinous differentiation. Int J Gynecol Pathol 39(5):493–497 PubMed DOI
Zapata M, Cohen C, Siddiqui MT (2007) Immunohistochemical expression of SMAD4, CK19, and CA19-9 in fine needle aspiration samples of pancreatic adenocarcinoma: utility and potential role. Cytojournal 4:13 PubMed DOI PMC
Ritterhouse LL et al (2019) Loss of SMAD4 protein expression in gastrointestinal and extra-gastrointestinal carcinomas. Histopathology 75(4):546–551 PubMed DOI
Hu Z et al (2020) The repertoire of serous ovarian cancer non-genetic heterogeneity revealed by single-cell sequencing of normal fallopian tube epithelial cells. Cancer Cell 37(2):226-242 e7 PubMed DOI
Immunohistochemical expression of PRAME in 485 cases of epithelial tubo-ovarian tumors
A comprehensive immunohistochemical analysis of 26 markers in 250 cases of serous ovarian tumors
A comprehensive immunohistochemical analysis of IMP2 and IMP3 in 542 cases of ovarian tumors