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

• Published in: Anticancer research Vol. 26; no. 6B; pp. 4597 - 4601
• Main Authors: SASIADEK, Maria M, SMIGIEL, Robert, STEMBALSKA, Agnieszka, RAMSEY, David, BLIN, Nikolaus
• Format: Journal Article
• Language: English
• Published: Attiki International Institute of Anticancer Research 01.11.2006
• Subjects: Adaptor Proteins, Signal Transducing; Biological and medical sciences; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Carrier Proteins - metabolism; Chromosomal Instability; Cyclin D1 - metabolism; Down-Regulation; Female; Humans; Immunohistochemistry; Laryngeal Neoplasms - genetics; Laryngeal Neoplasms - metabolism; Male; Medical sciences; MutL Protein Homolog 1; Nuclear Proteins - metabolism; Nucleic Acid Hybridization; Otorhinolaryngology. Stomatology; Tumors; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; Chromosomal aberration; Laryngeal cancer; microsatellite instability; Larynx cancer; Cyclin D1; DNA repair; Repair gene; Cancerology; Base mismatching; Microsatellite DNA; Cell cycle; ENT disease; Genetics; Larynx disease; chromosomal inbalance; Protooncogene; DNA mismatch repair; Chromosome; Malignant tumor; Gene expression; MLH1; Comparative genomic hybridization; C-Onc gene; cyclin Dl; Instability
• ISSN: 0250-7005; 1791-7530

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.