Abstract 688: Lamin A/C a novel potential prognostic marker in early operable primary breast cancer

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Abstract Background Lamins A/C, a major component of the nuclear lamina of highly differentiated mammalian cells is encoded by LMNA gene. Its involvement in tumorignesis is of interest due to its role in maintaining the nuclear integrity, regulation of gene expression, cell proliferation and apoptosis. Reduced lamin A/C expression in cancer has been reported to be a sign of poor prognosis. However there is few data on its clinical significance in breast cancer. This study aimed to evaluate expression of lamin A/C in a large series of patients with early operable invasive breast cancer; we analyzed the association of lamin A/C expression with clinicopathological parameters and long term clinical outcome. Methods Using immunohistochemistal staining of tissue microarrays, expression of Lamin A/C was evaluated in a large well characterized series of early operable invasive breast carcinoma patients (n=938) obtained from Nottingham Tenovus Primary Breast Carcinoma Series between the period of 1988 and 1998 who underwent primary surgery. All patients were managed following a standard management guidelines by a single team of clinicians and the decision of adjuvant systemic therapy was made on the basis of Nottingham prognostic Index (NPI) score and hormonal status. Using X-tile bioinformatics software a positivity cut-off of H-score >150 was found to be most informative. The expression was then correlated with clinicopathological parameters (age, tumour grade, tumour stage, tumour size, nodal status, vascular invasion, and NPI) using Chi-squared analyses. Association of lamin A/C expression with prognosis [loco-regional recurrence, distant metastasis and breast cancer specific survival (BCSS)] was evaluated by Kaplan Meier survival analysis and Cox proportional hazards model was used to assess the statistical independence and significance of the marker on BCSS. Results The median follow-up of patients was 146 months. Positive expression rate of Lamin A/C was 42.2%. (n=398). Lamin A/C expression was significantly associated with low histological grade (p<0.001), tumour size <1.5 cm (p=0.004), good NPI score (p<0.001), absence of vascular invasion (p=0.014) and absence of distant metastasis (p = 0.027). No association was found between cells expressing lamin A/C and lymph node stage, distant metastases, loco-regional recurrence and patient age. Survival analysis showed that lamin A/C positivity was significantly associated with a longer breast cancer specific survival (p = 0.008) but it was not independent of tumour stage, grade or size for predicting BCSS (p=0.304). Conclusion This study suggests lamin A/C expression as a potential prognostic biomarker for early operable invasive breast cancer. Our findings indicate that lamin A/C expressing tumours are associated with better breast cancer specific survival. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 688. doi:1538-7445.AM2012-688