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.
Highlights
Cervical cancer is the fourth most common cancer in women and the seventh overall, with an estimated 528,000 new cases and 266,000 deaths in 2012, accounting for 7.5% of all cancer deaths in females [1]
In locally advanced cervical cancer (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)
We found that the pathological tumor response to chemoradiation was significantly reduced in tumors with low- versus highprelamin A level in pre-treatment biopsy tissues; likewise, high RAD51 was associated with a significantly lower rate of pathological complete response compared to tumors with low expression
Summary
Cervical cancer is the fourth most common cancer in women and the seventh overall, with an estimated 528,000 new cases and 266,000 deaths in 2012, accounting for 7.5% of all cancer deaths in females [1]. Concurrent chemoradiation has significantly improved disease control and survival, patients in advanced stage of cervical cancer are at greater risk of recurrence and account for the majority of deaths, with a 5-year overall survival of about 70% [5,6,7] In this context, investigational approaches using either neoadjuvant chemotherapy (NACT) or CT/RT followed by radical surgery (RS) have reported encouraging results in terms of clinical outcome, with acceptable toxicity [8,9,10,11,12,13]. According to recently published data, EGFR signaling, C-erbB-2, and COX-2 could represent interesting indicators of poor response to chemoradiation [7], but to date, no one single biomarker has achieved combined sensitivity and specificity values across the breadth of clinical presentations
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
