DETECTION OF CLONALITY AND GENETIC ALTERATIONS IN ENDOMETRIAL PIPELLEBIOPSY AND ITS SURGICAL SPECIMEN COUNTERPART

Carcinoma of the endometrium is the most frequently diagnosed gynecolo gic malignancy in the western world. Because endometrial carcinoma is monoclonal in origin, the small samples obtained in endometrial pipell e biopsies can be used in PCR clonal studies to distinguish cancerous from noncancerous lesions. The method used for clonal analysis was bas ed on RFLP of the X chromosome-linked phosphoglycerokinase gene and ra ndom inactivation of one X chromosome by methylation in women. Among 5 0 endometrial pipelle biopsies, 26 (52%) were found to be heterozygous for the above-mentioned polymorphism. Of the samples taken from these informative (ie, heterozygous) patients, six were monoclonal includin g five cases of endometrial carcinoma and one of endometrial atypical hyperplasia. In each case, the same pattern of monoclonality was prese nt in the surgical specimen counterpart. All of the remaining samples were polyclonal and, when the anatomical pathology data were contraste d, they correlated with nonmalignant endometrium (five secretory, five proliferative, seven atrophic, and three simple hyperplasias). In add ition, genetic alterations study of monoclonal endometrial samples rev ealed a K-ras point mutation and a c-erbB2/neu gene amplification in t wo different endometrial carcinomas. Both alterations were also detect ed in the surgical specimens. In addition, a diagnosed set of 10 sampl es of simple hyperplasia and 5 of atypical hyperplasia were subjected to clonal assay. Among eight informative cases, the three that showed the monoclonal pattern corresponded with cases of atypical hyperplasia . No other genetic alterations were detected in these samples. In conc lusion, our data indicate that the detection of clonality in endometri al biopsy samples obtained by pipelle would be a useful application fo r the early diagnosis of endometrial cancer.