Kersemaekers A M, Fleuren G J, Kenter G G, Van den Broek L J, Uljee S M, Hermans J, Van de Vijver M J
Department of Pathology, Leiden University Medical Center, The Netherlands.
Clin Cancer Res. 1999 Mar;5(3):577-86.
The involvement of human papillomavirus (HPV) in the development of carcinomas of the uterine cervix has been firmly established. However, other genetic alterations also play an important role in the pathogenesis of cervical cancer. Therefore, we have investigated the role of several (onco)genes in cervical carcinoma. In tumors from 136 patients with stage I and II cancer of the uterine cervix, the expression of epidermal growth factor receptor (EGFR), c-erbB-2/neu, p53, and murine double minute 2 (MDM-2) was studied using immunohistochemistry. In 32 cases, amplification of EGFR, c-erbB-2/neu, MDM-2, and c-myc was studied by Southern blot hybridization. The expression levels of these proteins were correlated with HPV positivity, International Federation of Gynecologists and Obstetricians stage, lymph node metastases, tumor diameter, vessel invasion, and disease-free and overall survival. Moderate/strong expression of EGFR was observed in 54% of tumors. c-erbB-2/neu was focally positive in 12 cases. p53 showed moderate/strong expression in 32% of the tumors. Thirteen % of tumors showed a moderate/strong expression of MDM-2, and this expression was correlated to p53 expression (P<0.001). Only moderate/strong expression of EGFR was associated with reduced disease-free (P = 0.002) and overall survival (P = 0.003). In multivariate analysis, the association of EGFR overexpression with poor prognosis was independent from lymph node status. Gene amplification was found for EGFR (four cases), c-erbB-2/ neu (two cases), and c-myc (six cases). In two tumors, rearrangement of c-myc was found, probably due to the integration of HPV. In conclusion, overexpression of the EGFR is an independent predictor for prognosis in earlier stages (stage I and II) of cervical cancer. p53 and MDM-2 expression are correlated to each other and may play a role in the interaction with HPV. The importance of c-erbB-2/neu and c-myc amplification is relatively small in stage I and II cervical cancer.
人乳头瘤病毒（HPV）与子宫颈癌的发生之间的关联已得到确凿证实。然而，其他基因改变在宫颈癌的发病机制中也起着重要作用。因此，我们研究了几种（癌）基因在宫颈癌中的作用。采用免疫组织化学方法，对136例I期和II期子宫颈癌患者肿瘤组织中表皮生长因子受体（EGFR）、c-erbB-2/neu、p53和鼠双微体2（MDM-2）的表达进行了研究。在32例病例中，通过Southern印迹杂交研究了EGFR、c-erbB-2/neu、MDM-2和c-myc的基因扩增情况。这些蛋白的表达水平与HPV阳性、国际妇产科联合会分期（FIGO分期）、淋巴结转移、肿瘤直径、血管浸润以及无病生存期和总生存期相关。5
