Inverse correlation between Lamin A/C and survival in ovarian cancer: implications for predicting responsiveness to taxane-based chemotherapy.

OBJECTIVE: Although paclitaxel is widely used to treat several solid cancers, the initial response rate in ovarian cancer is ∼60 %, but only ∼30 % in recurrent ovarian cancer. The basis of resistance remains poorly understood, and predictive biomarkers are currently unavailable. Nuclear Lamin A/C proteins determine the sturdiness of the nuclear envelope and were suggested to influence the sensitivity of the malignant cells to undergo paclitaxel-induced micronucleation and cell death. The relationship between Lamin A/C expression in ovarian cancer tissues and progression free survival (PFS) and overall survival (OS) in advanced ovarian cancer patients, most of whom had been treated at least once with platinum and taxane, was investigated. METHODS: Ovarian cancer samples in tumor microarrays were immunostained for Lamin A/C and analyzed for Lamin A/C expression in tumor cells. On the basis of this expression, tumors were stratified as either Lamin A/C-low or Lamin A/C-high. Overall survival and PFS were assessed using Kaplan-Meier plots. RESULTS: Both age and Lamin A/C expression correlate with OS, where older (> 60 years) and higher Lamin A/C expression aligned with lower survival. Lamin A/C expression was a predictor of OS independently of age. The median OS for the Lamin A/C-low group was 58 months versus 34.5 months for the high-expression group. CONCLUSIONS: A significant correlation was found between Lamin A/C expression and OS, which implies that strong, widespread Lamin A/C expression in primary tumor tissues may be a predictive marker for paclitaxel sensitivity and thus survival, supporting a proposed paclitaxel mechanism in inducing micronucleation of cancer cells.