Granulin-epithelin precursor is a novel prognostic marker in epithelial ovarian carcinoma
Granulin-epithelin precursor is a novel prognostic marker in epithelial ovarian carcinoma
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DOI：
10.1002/cncr.20219
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发表时间：
2004-05-15
期刊：
影响因子：
6.2
通讯作者：
Kohn, EC
中科院分区：
文献类型：
--
作者：
Davidson, B;Alejandro, E;Kohn, EC
背景资料。颗粒蛋白前体(GEP)在浸润性卵巢肿瘤组织中的表达明显高于交界性卵巢肿瘤组织。本研究的目的是探讨GEP在晚期卵巢癌组织中的定位表达及其与临床病理参数和生存期的关系。方法：采用免疫组织化学方法，对190例卵巢癌渗出液、相应的原发肿瘤标本和125例转移灶标本进行免疫组织化学分析。结果：190例胸腔积液中有171例(90%)的肿瘤细胞中检测到GEP，并同时显示了灶性细胞膜和细胞质的定位。间皮细胞多为GEP阳性(81%)。189例肿瘤活检标本中有180例(95%)癌细胞表达GEP，其中93例(52%)有间质细胞表达，124例(67%)有内皮细胞表达。在化疗过程中或化疗后的转移灶中，基质细胞中GEP的表达较低(P=0.034)。未经治疗的原发肿瘤标本中GEP阳性间质细胞的存在与总体生存不良有关(P=0.014)。结论：GEP在卵巢癌原发灶和转移灶组织中均有表达，在恶性积液中表达下调。与间质GEP表达相关的不良预后提示这种生长因子在卵巢癌中的预后作用。由美国癌症协会于2004年出版。*
BACKGROUND. The granulin-epithelin precursor (GEP) was preferentially expressed in invasive ovarian tumor epithelium specimens compared with specimens of borderline ovarian tumors. The objective of the current study was to evaluate the anatomic site-related and cellular expression of GEP and its association with clinicopathologic parameters and survival in patients with advanced-stage ovarian carcinoma.METHODS. Effusions (n = 190), corresponding primary tumor specimens (n = 64), and specimens of metastatic lesions (n = 125) were analyzed using immunohistochemistry with a specific polyclonal antipeptide antibody. In addition, 36 effusions were analyzed using immunoblotting.RESULTS. GEP was detected in tumor cells in 171 of 190 (90%) effusions and demonstrated both focal membrane and cytoplasmic localization. Mesothelial cells were often GEP positive (81%). GEP was found in carcinoma cells in 180 of 189 (95%) tumor biopsy specimens, with stromal and endothelial cell expression in 93 of 180 (52%) and 124 of 185 (67%) specimens, respectively. Lower GEP expression in stromal cells was observed in metastases sampled during or after chemotherapy (P = 0.034). The presence of GEP-positive stromal cells in untreated primary tumor specimens correlated with worse overall survival (P = 0.014). Significantly more frequent GEP expression was observed in tumor cells of both primary (P = 0.002) and metastatic (P < 0.001) tissue specimens compared with malignant effusions.CONCLUSIONS. GEP expression was observed in primary and metastatic epithelial ovarian carcinoma specimens, with down-regulated expression in tumor cells of malignant effusions. The poor outcome associated with stromal GEP expression suggests a prognostic role for this growth factor in ovarian carcinoma. Published 2004 by the American Cancer Society.*