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Clinical Cancer Research Vol. 6, 1410-1414, April 2000
© 2000 American Association for Cancer Research


Molecular Oncology, Markers, Clinical Correlates

Allelic Loss and Microsatellite Alterations of Chromosome 3p14.2 Are More Frequent in Recurrent Cervical Dysplasias1

W. Michael Lin, Eugenia A. Michalopulos, Nina Dhurander, Pui C. Cheng, William Robinson, Raheela Ashfaq, Robert L. Coleman and Carolyn Y. Muller2

Departments of Obstetrics and Gynecology [W. M. L., R. L. C., C. Y. M.] and Pathology [R. A.] and the Hamon Center for Therapeutic Oncology Research [W. M. L., E. A. M., C. Y. M.], University of Texas Southwestern Medical Center, Dallas, Texas 75235, and Departments of Obstetrics and Gynecology [P. C. C., W. R.] and Pathology [N. D.], Tulane University Hospital, New Orleans, Louisiana 70112

Epidemiological studies have documented the unpredictable clinical progression or recurrence of cervical dysplasia. Recent studies have shown several molecular changes in cervical cancers and their associated dysplasia. We conducted molecular analyses on a retrospectively ascertained cohort of recurrent and nonrecurrent cervical dysplasia cases in an attempt to define molecular biomarkers to predict progressive or recurrent disease. Cases were chosen if long-term follow-up (3–5 years after conization) and biopsy confirmation were available. Paraffin-embedded, postconization cervical tissues from 19 recurrent and 18 nonrecurrent dysplasias were analyzed. Human papillomavirus (HPV) was identified by PCR for general and type-specific (HPV-16 and HPV-18) primers. Allelotyping analysis was performed by multiplex PCR using a panel of 16 microsatellite markers targeting putative tumor suppressor gene regions on chromosomes 3p, 5p, 6p, 9p, 11q, and 17p. The overall rate of HPV infection was similar in both groups. In the allelotyping analysis, loss of heterozygosity at the fragile histidine triad region in 3p14.2 was significantly higher in the recurrent group than in the nonrecurrent group (P = 0.005). Furthermore, microsatellite alterations (MAs) were more frequent in the recurrent group (mean MA index, 0.254) as compared with the nonrecurrent group (mean MA index, 0.085; P = 0.0025). These findings suggest that HPV status alone does not predict recurrence and that loss of heterozygosity at the fragile histidine triad region may represent a potential biomarker in predicting recurrence. Frequent MAs in the recurrent group may represent an underlying genomic instability that creates susceptibility for allelic loss, thus increasing the risk for recurrence or progression.




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D. C. Connolly, D. L. Greenspan, R. Wu, X. Ren, R. L. Dunn, K. V. Shah, R. W. Jones, F. X. Bosch, N. Muñoz, and K. R. Cho
Loss of Fhit Expression in Invasive Cervical Carcinomas and Intraepithelial Lesions Associated with Invasive Disease
Clin. Cancer Res., September 1, 2000; 6(9): 3505 - 3510.
[Abstract] [Full Text]




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Copyright © 2000 by the American Association for Cancer Research.