Abstract
Several members of the KLK family have been proposed to modulate various tumor-relevant processes. Previously, we have shown that in advanced high-grade serous ovarian cancer tissue high KLK11 mRNA levels were significantly associated with prolonged overall and progression-free patients' survival. Furthermore, KLK11 mRNA expression positively correlated with KLK10 mRNA. In the present study, we examined the prognostic value for both KLK10 and KLK11 on the protein expression level by immunohistochemistry (IHC). A cohort encompassing 159 patient tumor samples afflicted with advanced high-grade (FIGO III/IV) serous ovarian cancer, present on tissue microarrays (TMA), was analyzed. For estimation of KLK10 and KLK11 immunoreactivity, an automated digital IHC image analysis algorithm was selected to quantify the antibody staining intensity in the tissues via an immunoreactive score (IRS). In line with the results obtained by mRNA analysis, KLK10 protein expression values were significantly and positively correlated with KLK11 protein expression values. In Kaplan-Meier analyses, both elevated KLK10, KLK11, and the combination of KLK10 and KLK11 protein levels were significantly linked with prolonged overall survival (OS). The addition of KLK10, KLK11 or the KLK10+KLK11 combination IRS to the base model in multivariate Cox analysis demonstrated that high KLK11 and KLK10+KLK11 protein expression levels, apart from clinical parameters, remained favorable independent predictive markers for OS. In conclusion, in the present study, we have validated the coordinate expression of KLK10 and KLK11 in advanced high-grade serous ovarian cancer. Furthermore, both increased KLK10 and KLK11 protein expression is associated with favorable prognosis in this major ovarian cancer subtype. The combined KLK10+KLK11 marker performed even stronger than KLK10 or KLK11 alone.