Kallikrein 5 overexpression is associated with poor prognosis in uterine cervical cancer

Objective: Kallikrein 5 (KLK5), which is frequently observed in normal cervico-vaginal fluid, is known to be related to prognosis in several solid tumors. We investigated the prognostic significance of KLK5 in uterine cervical cancer using tumor tissue microarray and immunohistochemistry staining. Methods: We analyzed samples of165 patients with uterine cervical cancer who received definitive radiation therapy between 2004 and 2012. We divided patients into two groups stratified by their KLK5 activity by immunohistochemistry staining: negative/weak (0-1+) (n=120 patients) and moderate/strong (2-3+) group (n=45 patients). Patient and tumor characteristics, patterns of failure, and survival outcomes were compared. Univariable and multivariable analyses were performed to identify prognostic factors. Results: Patients with KLK5 2-3+ were younger (median: 52 vs. 60 years) and had frequent paraaortic lymph node involvement (40.0% vs. 18.3%) than those with KLK5 0-1+. With a median follow-up of 60.8 (interquartile range, 47.5-77.9) months, patients with KLK5 2-3+ had inferior 5-year locoregional recurrence-free survival and distant metastasis-free survival of 61.7% (vs. 77.5% in KLK5 0-1+ group) and 59.4% (vs. 72.8% in the KLK5 0-1+ group), respectively (all p<0.05). KLK5 2-3+ expression retained its significance after adjusting for other well-known prognostic factors of tumor size and stage in multivariable analysis. Conclusions: KLK5 overexpression is associated with the aggressiveness of cervical cancer and may underlie the diminished response to conventional treatments. Therefore, KLK5 could be a reliable prognostic factor in cervical cancer.