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卵巢癌中耐药相关蛋白的免疫组织化学分析

Immunohistochemical analysis of drug resistance-associated proteins in ovarian carcinomas.

作者信息

Mayr D, Pannekamp U, Baretton G B, Gropp M, Meier W, Flens M J, Scheper R, Diebold J

机构信息

Pathological Institute, University of Munich, Germany.

出版信息

Pathol Res Pract. 2000;196(7):469-75. doi: 10.1016/S0344-0338(00)80048-5.

DOI:10.1016/S0344-0338(00)80048-5
PMID:10926324
Abstract

Loss of function of the tumor suppressor gene p53, increased expression of glutathione-S-transferase pi (GST7pi) and the major vault protein are involved in drug resistance of ovarian carcinomas. However, a study comparing these factors has not yet been performed. Therefore, paraffin-embedded material of 213 ovarian tumors with well-documented follow-up was used for immunohistochemical analysis of p53 protein, GSTpi, and major vault protein (antibodies LRP-56, LMR-5). Forty-six percent of the cases showed nuclear p53 accumulation. Strong immunoreactivity for GSTpi, LRP-56, and LMR-5 was seen in 50%, 36%, and 47%, respectively. p53 positivity was most often found in serous carcinomas (p < 0.05). Strong GSTpi expression was the only factor that correlated with clinical resistance to chemotherapy (p = 0.04). In the whole group, as well as in FIGO III cases stratified for residual disease < or = and >2 cm, p53 and GSTpi correlated with an adverse outcome (p = 0.01 for p53 and p = 0.04 for GSTpi). Strong LRP-56 or LMR-5 staining was associated with a tendency towards poorer prognosis, without reaching statistical significance. In multivariate analysis for FIGO III, only residual disease and p53 proved to be independent prognostic factors. Our observations confirm the prognostic significance of p53 accumulation in ovarian carcinomas. Only GSTpi immunoreactivity was significantly correlated with drug resistance.

摘要

肿瘤抑制基因p53功能丧失、谷胱甘肽-S-转移酶pi(GST7pi)表达增加以及主要穹窿蛋白与卵巢癌耐药有关。然而,尚未进行比较这些因素的研究。因此,对213例有详细随访记录的卵巢肿瘤石蜡包埋材料进行p53蛋白、GSTpi和主要穹窿蛋白(抗体LRP-56、LMR-5)的免疫组织化学分析。46%的病例显示p53核内积聚。GSTpi、LRP-56和LMR-5的强免疫反应性分别见于50%、36%和47%的病例。p53阳性最常见于浆液性癌(p<0.05)。GSTpi强表达是唯一与临床化疗耐药相关的因素(p = 0.04)。在整个组以及根据残留病灶<或=和>2 cm分层的FIGO III期病例中,p53和GSTpi与不良预后相关(p53为p = 0.01,GSTpi为p = 0.04)。LRP-56或LMR-5强染色与预后较差的趋势相关,但未达到统计学意义。在FIGO III期的多因素分析中,只有残留病灶和p53被证明是独立的预后因素。我们的观察结果证实了p53积聚在卵巢癌中的预后意义。只有GSTpi免疫反应性与耐药显著相关。

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