Jennings T S, Dottino P R, Mandeli J P, Segna R A, Kelliher K, Cohen C J
Department of Obstetrics, Gynecology and Reproductive Sciences, Mount Sinai Hospital, New York, New York 10029.
Gynecol Oncol. 1994 Nov;55(2):190-7. doi: 10.1006/gyno.1994.1276.
Both epidermal growth factor receptor (EGFR) and HER-2/neu (neu) have been found to be of prognostic importance in epithelial ovarian and endometrial carcinoma, but alterations in proto-oncogene expression of normal tissues of patients with gynecologic malignancies are unknown. Patients (118) undergoing laparotomy for gynecologic indications (78 ovarian cancer, 11 endometrial cancer, 19 benign gynecologic disease, 10 other cancers) had biopsies of normal peritoneum for quantitative assessment of neu and EGFR concentrations. Patients undergoing exploration for gynecologic malignancy were found to have significantly higher median neu expression in the peritoneal biopsies than patients with benign gynecologic disease (P = 0.002). Most patients in this study were found to have ovarian cancer, and median peritoneal neu expression was found to be significantly higher in patients with ovarian cancer versus benign ovarian masses (P = 0.0008) or any benign gynecologic disease (P = 0.004). No significant alteration of unbound EGFR was found in peritoneal biopsies of any of the groups of patients. No associations were found for a history of breast cancer, presence of ascites, or menopausal status with alteration of neu or EGFR expression in normal peritoneum. These findings of altered expression of neu in normal tissues of patients with ovarian cancer are suggestive of the presence of proto-oncogene alterations in loco-regional tissues of the peritoneum, such as might be seen if a paracrine influence existed between tumor and peritoneal cells. Alternatively, the alterations may represent subtle alterations of proto-oncogene expression of germ-line tissues.
表皮生长因子受体(EGFR)和HER-2/neu(neu)已被发现对上皮性卵巢癌和子宫内膜癌具有预后重要性,但妇科恶性肿瘤患者正常组织中原癌基因表达的改变尚不清楚。因妇科指征接受剖腹手术的患者(118例)(78例卵巢癌、11例子宫内膜癌、19例良性妇科疾病、10例其他癌症)取正常腹膜活检组织,用于定量评估neu和EGFR浓度。结果发现,接受妇科恶性肿瘤探查的患者腹膜活检组织中的neu表达中位数显著高于良性妇科疾病患者(P = 0.002)。本研究中的大多数患者为卵巢癌患者,且发现卵巢癌患者腹膜neu表达中位数显著高于良性卵巢肿块患者(P = 0.0008)或任何良性妇科疾病患者(P = 0.004)。在任何一组患者的腹膜活检组织中均未发现未结合EGFR有显著改变。未发现乳腺癌病史、腹水情况或绝经状态与正常腹膜中neu或EGFR表达改变之间存在关联。卵巢癌患者正常组织中neu表达改变的这些发现提示腹膜局部区域组织中存在原癌基因改变,例如如果肿瘤与腹膜细胞之间存在旁分泌影响时可能会出现这种情况。或者,这些改变可能代表种系组织原癌基因表达的细微改变。