Cyclin D1 and MLH1 Levels in Laryngeal Cancer are Linked to Chromosomal Imbalance

Abstract

Background: Carcinogenesis results from the accumulation of genetic alterations forming a functional network leading to genetic instability as a cardinal feature. Thus, the hypothesis that down-regulation of MLH1 in combination with aberrant cell cycle control may contribute to chromosomal instability in LSCC was tested. Patients and Methods: Fifty-two patients, diagnosed with primary LSCC, none of whom had a history of hereditary cancer, were evaluated by comparative genomics. The expression of selected proteins controlling the cell cycle and mismatch repair was assessed with immunostaining. Results: In our set, 1720 chromosomal imbalances were found, as well as altered protein synthesis including a decrease in RB1 and CDKN2A (10.2% and 44% of cases, respectively), an increase in CCND1 (47%) and a decrease in MLH1 (22.7%). Variation analysis correlating proteins, chromosomal imbalances and clinicohistopathological features of disease disclosed an association between chromosomal gains, low histopathological grade of tumour and CCND1 over-expression accompanied by a decrease in MLH1 expression (p<0.01). Conclusion: CCND1 and MLH1 seem functionally interconnected in regard to chromosomal imbalances in larynx cancer.