Keratin 17 Identified as Negative Prognostic Marker in High-Grade Endometrial Cancer
Both mRNA analysis from TCGA data (271 patients) and immunohistochemistry on an independent cohort (119 patients) confirmed that high keratin 17 expression correlates with decreased overall survival in high-grade endometrial carcinoma (HR 1.8 in both analyses). K17 was specific to malignant glandular cells with no staining in stroma, myometrium, or sarcoma. For pathology labs, K17 IHC could serve as a straightforward prognostic add-on to routine endometrial cancer workup, building on its established role in cervical and ovarian cancers.
The original study
Keratin 17 is a negative prognostic biomarker in high-grade endometrial carcinomas.
- Authors
- Bai JDK, Babu S, Roa-Peña L, Hou W, Akalin A, Escobar-Hoyos LF, et al.
- Journal
- Human pathology
- Type
- Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't
- PMID
- 31655172
Original abstract
Keratin 17 (K17) has been established as a negative prognostic biomarker in cervical and ovarian cancers but has not previously been evaluated as a prognostic biomarker in endometrial adenocarcinoma. The association of K17 with decreased patient survival may be explained in part by the discovery that K17 drives tumor aggression by serving as a nuclear shuttle of p27, leading to cell cycle progression and tumor growth. The current study tests the hypothesis that K17 mRNA and protein levels correlate with decreased survival of patients with high-grade endometrial cancer. Gene expression data (mRNA) from The Cancer Genome Atlas were analyzed for 271 high-grade endometrial carcinomas and K17 immunohistochemistry (IHC) was performed on a separate cohort of 119 high-grade endometrial cancer cases from two academic medical centers. Survival analyses were determined by Cox proportional hazards regression. High K17 mRNA and IHC correlated with decreased overall survival (HR: 1.8, P = .0101, HR: 1.8, P = .0488, respectively). K17 was positive in malignant glandular cells of the endometrium but not in other tissues, including endometrial stroma, myometrium and uterine sarcoma. These results support the conclusion that K17 is a negative prognostic biomarker in high-grade endometrial carcinoma and that K17 IHC test results could be used to inform decisions related to therapeutic intervention.