Microsatellite instability, expression of hMSH2 and hMLH1 and HPV infection in cervical cancer and their clinico-pathological association

Infection with specific genotypes of human papillomavirus (HPV) has been st rongly implicated in cervical carcinogenesis. However, HPV infection alone is insufficient for malignant transformation of the cervical epithelium. An alteration of microsatellite repeats is the result of slippage owing to st rand misalignment during DNA replication and is referred to as microsatelli te instability (MSI). These defects in DNA repair pathways have been relate d to human carcinogenesis; however, the role of MSI in the tumorigenesis of cervical cancer remains unclear. The clinical and pathological features of cervical cancers which are MSI-positive have also not been fully character ized. This study investigated the prevalence of MSI in cervical cancer and its relationship to clinico-pathological characteristics and HPV infection. Polymerase chain reaction-based microsatellite assay combined with tissue microdissection was used to examine for MSI in 50 cervical squamous cell ca rcinomas in Hong Kong women. In addition, the immunohistochemical staining was performed to determine the expression of major DNA mismatch repair gene s, hMSH2 and hMLH1. Six cases (12%) displayed a low frequency of MSI (MSL-L ) showing MSI at one locus only in 5 loci examined. Seven cases (14%) showe d a high frequency of MSI (MSI-H) having MSI at 2 or more loci. Grouping MS I-L and MSI-H cases together as MSI-positive, statistical analysis of HPV i nfection, tumor grade, clinical stage and clinical status failed to disclos e differences between SI-positive and MSI-negative cases (p > 0.05). Howeve r, MSI-H correlated with advanced stage of disease (p < 0.05). Individuals with MSI-H tumors appeared to have reduced overall survival compared to ind ividuals with MSI-L and MSI-negative tumors, but the difference was not sta tistically significant (p = 0.059). An absence of either MSH2 or MLH1 expre ssion was observed in 2 MSI-L and 4 MSI-H cases, respectively. The results suggest that MSI is present in a subgroup of cervical squamous cell carcino mas, and defects resulting in MSI may be related to tumor progression and p ossibly poor prognosis in cervical cancer. Copyright (C) 2001 S. Karger AG, Basel.