POTENTIAL BIOMARKERS IN PREDICTING PROGRESSION OF EPITHELIAL HYPERPLASTIC LESIONS OF THE LARYNX

Factors contributing to malignant transformation of laryngeal pre-neop lastic lesions remain largely unknown. potential etiologic factors may be related to a genetically controlled sensitivity to environmental c arcinogens. In this study, we investigated bleomycin-induced chromosom e fragility in 15 patients with laryngeal keratoses who experienced a malignant transformation of pre-neoplastic lesions during follow-up, a s compared with chromosome fragility in 15 historical controls with no progression of laryngeal keratoses during a 10-year follow-up, in a m atch-paired analysis. Chromosomal analysis demonstrated a higher sensi tivity to clastogens in patients with malignant progression of larynge al pre-neoplastic lesions than that of control patients with no evolut ion of their original laryngeal keratoses (p < 0.01). Furthermore, in the attempt to identify possible prognostic markers we studied prolife rative activity (MIB-1 expression) and p53 gene aberration in biopsy s amples from non-invasive and invasive laryngeal lesions in both groups . p53 immunostaining was observed in 10/15 (66.7%) of pre-neoplastic l esions and in 11/15 (73.3%) of metachronous laryngeal cancers. No diff erences in terms of p53 expression were noted between transformed and not-transformed lesions. Mutations at p53 gene were observed in 3/15 ( 20%) of pre-invasive biopsies and in 4/5 (80%) of the laryngeal cancer s analyzed. Our data suggest that p53 alteration is an early event in the genesis of a subset of laryngeal carcinomas and that there is no c onclusive data about the possible clonal development of metachronous l aryngeal carcinoma from a p53 mutated pre-invasive disease in the same patient. MIB-1 expression was found to progressively increase with de gree of epithelial hyperplasia and dysplasia in both transformed (p=0. 007) and not-transformed (p<0.1) lesions. Surprisingly, pre-invasive l esions with tumor evolution showed a lower proliferative activity when compared with laryngeal lesions without malignant transformation (p=0 .013). These data suggests that subjects with pre-neoplastic laryngeal lesion showing an increased susceptibility to carcinogens and with le ss proliferative disease could be at a higher risk for development of laryngeal carcinoma.