Abstract
Along with their role in the maintenance of nuclear architecture, nuclear lamins also control genomic stability, DNA damage repair, transcription, cell proliferation, differentiation and senescence. Recent reports reveal that prelamin A-processing defects play a role in cancer development by impacting on transcription of key players in the maintenance of the genome stability, including RAD51. Here, we performed a 'proof of concept' study evaluating the role of prelamin A and RAD51 expression in clinical outcome of cervical cancer patients. We analyzed biomarker expression by immunohistochemistry in tumor material from locally advanced cervical cancer (LACC) patients (n=66) and correlated data with clinicopathological parameters and with response to neoadjuvant chemoradiation (CT/RT). In LACC patients who underwent neoadjuvant CT/RT the percentage of cases showing high prelamin A levels was greater in patients who completely responded to treatment (25 of 40, 62.5%) than in patients with macroscopic residual tumor (6 of 26, 23.1%, p=0.0024). Conversely, patients showing high RAD51 expression were less likely to respond to treatment (14 of 26, 53.8%) than were those with low protein levels (12 of 40, 30%, p=0.072). Only prelamin A retained an independent role in predicting response to treatment (p=0.003), while RAD51 approached statistical significance (p=0.07). Notably, high RAD51 expression highly significantly predicted poor outcome, emerging as an independent prognostic factor for disease free survival (p=0.038), while approaching statistical significance for overall survival (p=0.09). Our findings provide a framework for future prospective studies investigating molecular predictors of response to neoadjuvant chemoradiotherapy in LACC patients.