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.