CORRELATION OF C-MYC AND HER-2 NEU AMPLIFICATION AND EXPRESSION WITH HISTOPATHOLOGIC VARIABLES IN UTERINE CORPUS CANCER/

OBJECTIVE: Initial studies of protooncogenes in uterine corpus cancer have focused on a single aspect of the gene in question (deoxyribonucl eic acid, ribonucleic acid, protein) or have studied a small number of patients. Therefore we evaluated c-myc and HER-2/neu gene amplificati on and ribonucleic acid overexpression in such malignancies and correl ated these molecular changes with known pathologic risk factors. STUDY DESIGN: Quantitative Southern blot analysis for oncogene deoxyribonuc leic acid was used to examine 37 tumors from patients with primary unt reated uterine corpus cancer referred to the City of Hope National Med ical Center, Six normal endometrial specimens were controls. Seventeen tumors were also examined by Northern blotting to assess increased ri bonucleic expression. RESULTS: Histologic types included adenocarcinom a (0 = 30), papillary serous adenocarcinoma (n = 2), adenosquamous car cinoma (0 = 2), mixed mullerian sarcoma (n = 2); and leiomyosarcoma (0 = 1). Carcinomas were stage I (0 = 10), II (0 = 18), or III (0 = 6). Twenty-three had myometrial invasion of less than one third, six one t hird to two thirds, and eight deeper invasion (greater than two thirds ). According to the criteria of the International Federation of Gyneco logy and Obstetrics stage was as follows: I (n = 22), II (n = 3), III (n = 7), and IV (n = 5). Ten (27%) and four (11%) tumors showed gene a mplification of c-myc and HER-2/neu, respectively. Six demonstrated ov erexpression of either the c-myc or HER-2/neu gene. HER-2/neu gene amp lification was associated more closely with overexpression. Stepwise l ogistic analysis demonstrated c-myc amplification to be associated wit h higher grade (p = 0.01). CONCLUSION: In this referral population, c- myc activation is more common than HER-2/neu activation in uterine cor pus cancer and is associated with tumors of higher grade.