Loss of lamin A/C expression in stage II and III colon cancer is associated with disease recurrence

• Published in: European journal of cancer (1990) 2011-08, Vol.47 (12), p.1837-1845
• Main Authors: Belt, E.J.Th, Fijneman, R.J.A, van den Berg, E.G, Bril, H, Delis-van Diemen, P.M, Tijssen, M, van Essen, H.F, de Lange-de Klerk, E.S.M, Beliën, J.A.M, Stockmann, H.B.A.C, Meijer, S, Meijer, G.A
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biological and medical sciences; Biomarker; Biomarkers, Tumor - analysis; Colon cancer; Colonic Neoplasms - chemistry; Colonic Neoplasms - pathology; Colonic Neoplasms - surgery; Disease recurrence; Disease-Free Survival; Female; Gene Expression Regulation, Neoplastic; Hematology, Oncology and Palliative Medicine; Humans; Immunohistochemistry; Lamin A/C; Lamin Type A - analysis; Male; Medical sciences; Microsatellite Instability; Middle Aged; Multivariate Analysis; Neoplasm Recurrence, Local - chemistry; Neoplasm Recurrence, Local - diagnosis; Neoplasm Staging; Netherlands; Odds Ratio; Pharmacology. Drug treatments; Predictive Value of Tests; Prognosis; Protein Array Analysis; Recurrence; Risk Factors; Tumors
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2011.04.025

Abstract Aim of the study Loss of the nuclear lamina protein lamin A/C (LMNA) has been observed in several human malignancies. The present study aimed to investigate associations between LMNA expression and clinical outcome in colon cancer patients. Patients and methods Clinicopathological data and formalin-fixed paraffin embedded tissues were collected from 370 stage II and III colon cancer patients. Tissue microarrays were constructed, stained for lamin A/C and evaluated microscopically. Microsatellite instability status was determined for 318 tumours. Results Low levels of LMNA expression were observed in 17.8% of colon tumours, with disease recurrence occurring in 45.5% of stage II and III colon cancer patients with LMNA-low expressing tumours compared to 29.6% of patients with LMNA-high expressing tumours ( p = 0.01). For stage II patients, disease recurrence was observed for 35.7% of LMNA-low compared to 20.3% of LMNA-high expressing tumours ( p = 0.03). Microsatellite stable (MSS) tumours exhibited more frequently low LMNA expression than microsatellite instable (MSI) tumours (21% versus 9.8%; p = 0.05). Interestingly, disease recurrence among LMNA-low and LMNA-high expressing MSS tumours varied significantly for stage III patients who had not received adjuvant chemotherapy (100% versus 37.8%; p < 0.01) while no such difference was observed for patients who received adjuvant chemotherapy (46.7% versus 46.0%; p = 0.96). Conclusion These data indicate that low expression of LMNA is associated with an increased disease recurrence in stage II and III colon cancer patients, and suggest that these patients in particular may benefit from adjuvant chemotherapy.