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Distinction of Low Grade from High Grade Human Ovarian Carcinomas on the Basis of Losses of Heterozygosity on Chromosomes 3, 6, and 11 and HER-2/neu Gene Amplification¹

Departments of Pathology [J. Z., L. D.], Gynecologic Oncology [W. R. R., T. E.], and Preventive Medicine [M. C. Y.], Kenneth Norris Jr. Comprehensive Cancer Center, University of Southern California School of Medicine, Los Angeles, California 90033

We examined the frequencies of loss of heterozygosity at 13 different loci distributed on 9 chromosomes in 30 human ovarian carcinomas. The same tumors were also examined for the presence of amplification of the HER-2/neu and H-ras protooncogenes. The results confirmed earlier findings that losses of heterozygosity occurred at nonrandom frequencies on chromosomes 3, 6, and 11 in these tumors. None of the tumors examined showed amplification at the H-ras locus. The HER-2/neu gene, however, was amplified in approximately one-third of the tumors, in agreement with earlier studies from other laboratories. We subdivided our tumor specimens according to their histological grades, which can be regarded as representing different stages of tumor progression. Losses of heterozygosity on chromosomes 3 or 11 were not seen in low grade lesions, although they were present in most of the high grade tumors examined. Losses of heterozygosity on chromosome 6 as well as HER-2/neu amplification, in contrast, were present in several low grade tumors and were not more frequent in high grade lesions. We conciude that the latter two abnormalities are associated with cellular functions involved at earlier stages of ovarian tumor development, whereas inactivation of genes on chromosome 3 or 11 is associated with later steps that may be incompatible with the well differentiated phenotype.

¹ Supported by Grant PDT375 from the American Cancer Society and by Grant R29 CA51167A from the National Cancer Institute.

² Present address: Department of Gynecologic Oncology, Wellesley Hospital, Toronto, Ontario M4Y 1J3, Canada.

³ To whom requests for reprints should be addressed.

Received 1/ 2/91. Accepted 5/22/91.

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