Correlation of C-myc and HER-2/neu amplification and expression with histopathologic variables in uterine corpus cancer

Abstract

Initial studies of protooncogenes in uterine corpus cancer have focused on a single aspect of the gene in question (deoxyribonucleic acid, ribonucleic acid, protein) or have studied a small number of patients. Therefore we evaluated c-myc and HER-2/neu gene amplification and ribonucleic acid overexpression in such malignancies and correlated these molecular changes with known pathologic risk factors. Quantitative Southern blot analysis for oncogene deoxyribonucleic acid was used to examine 37 tumors from patients with primary untreated uterine corpus cancer referred to the City of Hope National Medical Center. Six normal endometrial specimens were controls. Seventeen tumors were also examined by Northern blotting to assess increased ribonucleic expression. Histologic types included adenocarcinoma (n = 30), papillary serous adenocarcinoma (n = 2), adenosquamous carcinoma (n = 2), mixed mullerian sarcoma (n = 2), and leiomyosarcoma (n = 1). Carcinomas were stage I (n = 10), II (n = 18), or III (n = 6). Twenty-three had myometrial invasion of less than one third, six one third to two thirds, and eight deeper invasion (greater than two thirds). According to the criteria of the International Federation of Gynecology 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 amplification of c-myc and HER-2/neu, respectively. Six demonstrated overexpression of either the c-myc or HER-2/neu gene. HER-2/neu gene amplification was associated more closely with overexpression. Stepwise logistic analysis demonstrated c-myc amplification to be associated with higher grade (p = 0.01). In this referral population, c-myc activation is more common than HER-2/neu activation in uterine corpus cancer and is associated with tumors of higher grade.