Ikeda K, Sakai K, Yamamoto R, Hareyama H, Tsumura N, Watari H, Shimizu M, Minakami H, Sakuragi N
Department of Obstetrics and Gynecology, Hokkaido University School of Medicine, Sapporo, Japan.
Int J Gynecol Cancer. 2003 Nov-Dec;13(6):776-84. doi: 10.1111/j.1525-1438.2003.13381.x.
It has been suggested that histologic subtype of ovarian cancer is a factor that determines the chemoresponsiveness of tumor. In this study, we wanted to clarify the prognostic significance of histologic subtype and its correlation to expression of chemoresistance-related proteins (CRPs) in ovarian cancer. A total of 93 stage II-IV ovarian cancers, where the proportion of serous, endometrioid, mucinous, and clear cell subtype was 61.3%, 14.0%, 7.5%, and 17.2%, respectively, were investigated for glutathione S-transferase-pi (GST-pi), MDR (multidrug resistance)-1, and p53 expression using immunohistochemistry. GST-pi expression was detected in 62.4% of the tumors and was not related to histologic subtype of tumor. MDR-1 expression was observed in 12.9% of the tumors tested and was more frequently detected in clear cell adenocarcinomas than other histologic subtypes of tumor (10/ 16 vs. 2 / 77, P < 0.001). P53 expression was found in 49.1% of serous, 53.8% of endometrioid, and 50% of mucinous adenocarcinomas. In contrast, none of 16 clear cell adenocarcinomas showed positive p53 staining. In univariate analysis, no direct correlations were found between CRPs and overall survival. Histology of mucinous/clear cell tumors (P = 0.0063), as well as FIGO stage III/IV (P = 0.0091) and residual tumor >or= 2 cm (P = 0.0045), was found to have independent prognostic value in multivariate analysis. In conclusion, histologic subtype proved to be the significant independent prognostic factor in addition to FIGO stage and residual tumor in stage II-IV ovarian cancer. GST-pi, MDR-1, and p53 expression pattern is closely related to histologic subtype of ovarian cancer, although they are not significant predictors of survival.
有人提出,卵巢癌的组织学亚型是决定肿瘤化疗反应性的一个因素。在本研究中,我们想阐明组织学亚型的预后意义及其与卵巢癌中化疗耐药相关蛋白(CRPs)表达的相关性。我们使用免疫组织化学方法,对总共93例II-IV期卵巢癌进行了研究,其中浆液性、子宫内膜样、黏液性和透明细胞亚型的比例分别为61.3%、14.0%、7.5%和17.2%。检测了谷胱甘肽S-转移酶-pi(GST-pi)、多药耐药(MDR)-1和p53的表达。在62.4%的肿瘤中检测到GST-pi表达,且其与肿瘤的组织学亚型无关。在12.9%的检测肿瘤中观察到MDR-1表达,在透明细胞腺癌中比其他组织学亚型更频繁地检测到(10/16 vs. 2/77,P<0.001)。在49.1%的浆液性、53.8%的子宫内膜样和50%的黏液性腺癌中发现p53表达。相比之下,16例透明细胞腺癌中无一例p53染色呈阳性。在单因素分析中,未发现CRPs与总生存期之间有直接相关性。在多因素分析中,黏液性/透明细胞肿瘤的组织学(P = 0.0063)以及国际妇产科联盟(FIGO)III/IV期(P = 0.0091)和残留肿瘤≥2 cm(P = 0.0045)被发现具有独立的预后价值。总之,除了FIGO分期和残留肿瘤外,组织学亚型被证明是II-IV期卵巢癌的重要独立预后因素。GST-pi、MDR-1和p53的表达模式与卵巢癌的组织学亚型密切相关,尽管它们不是生存的重要预测指标。