High Keratin-7 Expression in Benign Peri-Tumoral Prostatic Glands Is Predictive of Bone Metastasis Onset and Prostate Cancer-Specific Mortality

SIMPLE SUMMARY: Keratin-7 overexpression has been associated with poor prognosis in several cancers. To determine its prognostic relevance in prostate cancer, cohorts of patients presenting with localized or advanced tumors were investigated by either immunohistochemistry or immunofluorescence. Keratin-7 immunostaining was absent in localized tumors and rare in advanced tumors. By contrast, it was abundantly detected in basal cells within benign glands surrounding localized tumors. Importantly, high keratin-7 expression in benign peri-tumoral glands was correlated with shorter bone metastasis-free survival and increased risk of cancer-specific mortality. This study establishes keratin-7 expression in localized prostate cancer specimens as a promising biomarker of disease progression. ABSTRACT: Background: New predictive biomarkers are needed to accurately predict metastasis-free survival (MFS) and cancer-specific survival (CSS) in localized prostate cancer (PC). Keratin-7 (KRT7) overexpression has been associated with poor prognosis in several cancers and is described as a novel prostate progenitor marker in the mouse prostate. Methods: KRT7 expression was evaluated in prostatic cell lines and in human tissue by immunohistochemistry (IHC, on advanced PC, n = 91) and immunofluorescence (IF, on localized PC, n = 285). The KRT7 mean fluorescence intensity (MFI) was quantified in different compartments by digital analysis and correlated to clinical endpoints in the localized PC cohort. Results: KRT7 is expressed in prostatic cell lines and found in the basal and supra-basal compartment from healthy prostatic glands and benign peri-tumoral glands from localized PC. The KRT7 staining is lost in luminal cells from localized tumors and found as an aberrant sporadic staining (2.2%) in advanced PC. In the localized PC cohort, high KRT7 MFI above the 80th percentile in the basal compartment was significantly and independently correlated with MFS and CSS, and with hypertrophic basal cell phenotype. Conclusion: High KRT7 expression in benign glands is an independent biomarker of MFS and CSS, and its expression is lost in tumoral cells. These results require further validation on larger cohorts.