Cyclin D1 and MLH1 levels in laryngeal cancer are linked to chromosomal imbalance.
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.


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).


CONCLUSIONS
CCND1 and MLH1 seem functionally interconnected in regard to chromosomal imbalances in larynx cancer.
Sasiadek
Maria M
MM
Department of Genetics, Wroclaw Medical University, Marcinkowskiego 1, 50-368, Wroclaw, Poland. sasiadek@gen.am.wroc.pl
Smigiel
Robert
R
Stembalska
Agnieszka
A
Ramsey
David
D
Blin
Nikolaus
N
D048868:Adaptor Proteins, Signal Transducing; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D043171:Chromosomal Instability; D019938:Cyclin D1 / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007822:Laryngeal Neoplasms / Q000235:genetics / Q000378:metabolism*; D008297:Male; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000378:metabolism*; D009693:Nucleic Acid Hybridization
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D019938:Cyclin D1; D000070957:MutL Protein Homolog 1