Molecular detection of cervical intraepithelial neoplasia and cervical carcinoma by microsatellite analysis of Papanicolaou smears

Carcinoma of the uterine cervix is one of the most common malignancies worl dwide, yet it is clearly preventable by population screening, The Papanicol aou (Pap) smear has proved to be the most successful test for the detection of precancerous lesions and is largely responsible for the reduction of ce rvical cancer mortality and morbidity rates. However, the Pap smear is not perfect; false-negative results of various rates are reported, To improve t he diagnostic efficacy of cervical cytology, we performed microsatellite an alysis on paired Pap smear samples from cervical lesions, Nine microsatelli te markers were chosen from chromosomal regions commonly displaying loss of heterozygostity (LOH) in cervical cancer and those displaying microsatelli te instability (MI) in other squamous cell cancer. Microsatellite alteratio ns were detected in 16/21 (76%) Pap smear DNA samples including 11 of 13 (8 5%) smears from invasive squamous cell carcinomas (SCCs) and 5 of 8 (63%) f rom squamous intraepithelial lesions (SILs), Microsatellite alterations det ected in the Pap smear DNA were identical to those identified in seven pair ed primary tumors available for analysis. Moreover, this molecular approach detected genetic alterations in two cases apparently negative by cytologic examination. None (0/25) of the control patients displayed microsatellite alterations in paired Pap smears. Microsatellite analysis of cervical cytol ogic samples may provide a complementary method to analyze suspicious but n ot diagnostic cytologic samples further, (C) 2001 Wiley-Liss, Inc.