Microsatellite instability is a late event in the carcinogenesis of uterine cervical cancer

The purpose of this study was to elucidate the role of genetic instability and LOH in the progression of cervical cancer and also to analyze for correlations between these genetic abnormalities and the clinicopathological characteristics of cervical cancers.

Seventy-two DNA samples were obtained from 29 carcinoma in situ, 8 microinvasive carcinoma, and 35 invasive cancers. Seven highly polymorphic microsatellite markers representing the chromosome 3p, 6p, and 6q arms were examined by PCR amplification.

Microsatellite instability was detected in 8 of 35 (22.9%) invasive cancers and in 1 of 37 (2.7%) early stage cancers (microinvasive cancer and carcinoma in situ). The incidence of MI was statistically higher in invasive cancers (P < 0.02). On the other hand, loss of heterozygosity (LOH) of chromosome 3p was identified in 6/41 (14.6%) invasive cancers and in 3/27 (11.1%) carcinomas in situ. There was no statistical difference between the two groups. There were no significant correlations between the presence of MI or 3p LOH and clinicopathological characteristics including the histological type, FIGO stage, depth of myometrial invasion, lymphovascular involvement, lymph node metastasis, and recurrence.

Our results indicate that genomic instability is a late event during the carcinogenesis of cervical cancer and is associated with the conversion of cervical intraepithelial neoplasia to an invasive phenotype. To the contrary, LOH of chromosome 3p plays an early role in the development of cervical intraepithelial neoplasia. No significant correlation was observed between the presence of MI or LOH and clinicopathological characteristics.