Allelic loss and microsatellite alterations of chromosome 3p14.2 are more frequent in recurrent cervical dysplasias

Epidemiological studies have documented the unpredictable clinical progress ion or recurrence of cervical dysplasia. Recent studies have shown several molecular changes in cervical cancers and their associated dysplasia. We co nducted molecular analyses on a retrospectively ascertained cohort of recur rent and nonrecurrent cervical dysplasia cases in an attempt to define mole cular biomarkers to predict progressive or recurrent disease, Cases were ch osen if long-term follow-up (3-5 years after conization) and biopsy confirm ation were available, Paraffin-embedded, postconization cervical tissues fr om 19 recurrent and 18 nonrecurrent dysplasias were analyzed, Human papillo mavirus (HPV) was identified by PCR far general and type-specific (HPV-16 a nd HPV-18) primers. Allelotyping analysis was performed by multiplex PCR us ing a panel of 16 microsatellite markers targeting putative tumor suppresso r gene regions on chromosomes 3p, 50, 6p, 9p, 11q, and 17p. The overall rat e of HPV infection was similar in both groups. In the allelotyping analysis , loss of heterozygosity at the fragile histidine triad region in 3p14.2 wa s significantly higher in the recurrent group than in the nonrecurrent grou p (P = 0.005). Furthermore, microsatellite alterations (MAs) were more freq uent in the recurrent group (mean MA index, 0.254) as compared with the non recurrent group (mean MA index, 0.085; P = 0.0025). These findings suggest that HPV status alone does not predict recurrence and that loss of heterozy gosity at the fragile histidine triad region may represent a potential biom arker in predicting recurrence. Frequent MAs in the recurrent group may rep resent an underlying genomic instability that creates susceptibility for al lelic loss, thus increasing the risk for recurrence or progression.