Thrombospondin-1 expression in epithelial ovarian carcinoma:: Association with p53 status, tumor angiogenesis, and survival in platinum-treated patients
Thrombospondin-1 expression in epithelial ovarian carcinoma:: Association with p53 status, tumor angiogenesis, and survival in platinum-treated patients
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DOI：
10.1006/gyno.2001.6287
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发表时间：
2001-08-01
影响因子：
4.7
通讯作者：
Rodriguez, GC
中科院分区：
文献类型：
--
作者：
Alvarez, AA;Axelrod, JR;Rodriguez, GC
目标。上皮性卵巢癌转移过程的调控机制尚未明确。与其他肿瘤类型相似，卵巢癌的血管生成表型强烈影响临床结果，提示获得促血管生成的环境对卵巢癌的增殖和转移过程是必不可少的。血栓反应蛋白-1(TSP-1)是一种在其他肿瘤系统中被发现与血管生成相关的有效多肽，可能受P53基因的调控，P53基因在高达50%的晚期卵巢癌中发生突变。本研究的目的是探讨TSP-1在卵巢浸润性上皮性癌中的表达及其与血管生成程度的关系。此外，我们还检测了TSP-1的表达是否与p53的过度表达有关。应用免疫组织化学方法检测85例卵巢浸润性上皮性癌冰冻切片中TSP-1和P53的表达。切片由两名研究人员进行显微镜检查，他们对临床病理变量视而不见。预后变量包括TSP-1、血管生成和P53之间的相关性，以及TSP-1表达与生存期之间的关系。大多数病例(62%)TSP-1高表达(3+)，7%无TSP-1表达。P53在55%的病例中过度表达，且表达与TSP-1染色呈负相关。13例癌组织呈0或1+TSP-1染色，其中12例(92%)P53蛋白过度表达。而在TSP-1高表达的肿瘤中，仅有49%的肿瘤有P53过表达(P=0.02)。TSP-1的高表达提示晚期疾病患者的中位生存期为2.4年，而TSP-1表达较低的肿瘤患者的中位生存期为1.5年(P=0.06)。提示TSP-1在晚期上皮性卵巢癌患者中可能具有抑瘤作用。TSP-1的表达降低与P53的过表达有关，可能与促血管生成环境和恶性表型的发展有关。(C)2001年学术出版社。
Objective. The regulation of the metastatic process in epithelial ovarian cancer has not been well defined. Similar to other tumor types, the angiogenic phenotype in ovarian cancer strongly influences clinical outcome, suggesting that the acquisition of a pro-angiogenic environment is essential to the process of ovarian cancer proliferation and metastasis. Thrombospondin-1 (TSP-1) is a potent peptide shown in other tumor systems to be associated with angiogenesis and possibly regulated by p53, a gene which is mutated in as high as 50% of advanced ovarian cancers. The purpose of this study was to investigate TSP-1 expression in invasive epithelial ovarian cancer and to examine the relationship between TSP-1 expression and the degree of angiogenesis. In addition, we examined whether TSP-1 expression was associated with overexpression of p53.Methods. Frozen sections obtained from 85 patients with invasive epithelial ovarian cancer were examined immunohistochemically for expression of TSP-1 and p53. The sections were examined microscopically by two investigators, who were blinded to the clinicopathologic variables. Outcome variables included the correlation among TSP-1, angiogenesis, and p53, as well as the association between TSP-1 expression and survival.Results. The majority (62%) of cases demonstrated high levels (3+) of TSP-1 expression; 7% demonstrated no TSP-1 expression. p53 was overexpressed in 55% of cases, and expression was inversely correlated with TSP-1 staining. Thirteen cancers had 0 or 1+ TSP-1 staining; 12 (92%) of these overexpressed the p53 protein. In contrast, only 49% of tumors with high expression of TSP-1 have overexpression of p53 (P = 0.02). TSP-1 was suggestive for improved survival in patients with advanced disease; high TSP-1 expression was associated with a median survival of 2.4 years compared to 1.5 years for patients with tumors having a lower degree of TSP-1 expression (P = 0.06).Conclusion. These data suggest that TSP-1 may possess a tumor inhibitory function in patients with advanced epithelial ovarian carcinoma. The reduction of TSP-1 expression associated with overexpression of p53 may be coupled with the development of a pro-angiogenic environment and malignant phenotype. (C) 2001 Academic Press.