Clinicopathologic and molecular markers in cervical carcinoma; a prospective cohort study

Abstract Background Cervical cancer is a major health problem worldwide. Identification of effective clinicopathologic and molecular markers is vital to improve treatment stratification. Objectives To validate a set of well-defined clinicopathologic features in a large population based, prospectively collected cervical cancer cohort to support their use in the clinic. Further, we explore p53 and HER2 as potential prognostic markers in cervical cancer. Study Design Tissue was collected from 401 cervical cancer patients. Clinical data including follow-up were collected from patient journals. Histopathologic data were evaluated and revised by an expert pathologist. Prognostic impact of selected clinicopathologic variables was analyzed in the whole cohort. Tissue microarrays (TMAs) were prepared from 292 carcinomas and p53 and HER2 protein levels were evaluated by immunohistochemistry. Fresh frozen samples from overlapping cervical carcinomas were previously subjected to HPV typing (n=94), whole exome (n=100) and RNA (n=79) sequencing, and results were available for our analyses. Results Among the clinicopathologic variables, vascular space invasion, histologic type and tumor size verified as strong independent prognostic markers. High p53 protein levels were significantly associated with markers for aggressive phenotype and survival, also in multivariate survival analysis, but did not reflect TP53 mutational status. High HER2 protein levels were identified in 21% of all tumors. ERBB2 amplification was associated with poor outcome (p = 0.003), HER2 protein level was not. Conclusions Our findings support that FIGO guidelines should include vascular space invasion and tumor size 2-4 cm and that careful selection of histologic type is essential for stratification of patient risk groups. High p53 independently predict poor survival, yet do not reflect mutational status in cervical cancer. Amplified ERBB2 significantly links to poor survival, while HercepTest do not. With optimal stratification, HER2-based therapy may improve cervical cancer treatment.