Cervical intraepithelial neoplasia: prognosis by combined LOH analysis of multiple loci.

OBJECTIVE Cervical intraepithelial neoplasias (CIN) show markedly variable clinical behavior. Clinically, it is important to distinguish CIN lesions with different behaviors and identify those likely to persist and progress. The purpose of this study is to explore whether CIN lesions with different clinical behaviors can be stratified by analysis of loss of heterozygosity (LOH) at multiple loci. METHODS One hundred sixty-four cases of CIN (54 CIN1, 59 CIN2 and 51 CIN3) were screened for LOH at 12 microsatellite markers including 10 from 3p14, 3p21-22, 6p21 and 11q23. LOH was correlated with clinical follow-up data and high-risk HPV infection. RESULTS In a pilot study of 71 cases of CIN, screening of 12 microsatellite markers identified four (D3S1300, D3S1260, D11S35, and D11S528) at which LOH was significantly associated with disease persistence/progression. These four markers were further investigated in a larger cohort, which brought the total number of cases examined to 164. Combined analysis of LOH at the above four loci permitted the identification of 22-47% of CIN lesions depending on the histological grade, which showed disease persistence/progression. LOH at these loci was significantly associated with HPV16 infection. Bioinformatic analysis identified several candidate genes including the fragile histidine triad gene and progesterone receptor gene that may be the target of deletions. CONCLUSIONS LOH at D3S1300, D3S1260, D11S35 and D11S528 was significantly associated with cins that showed persistence/progression, and combined LOH analyses at these loci could be used to identify such cases.

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