M-cam expression as marker of poor prognosis in epithelial ovarian cancer
M-cam expression as marker of poor prognosis in epithelial ovarian cancer
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DOI：
10.1002/ijc.22082
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发表时间：
2006-10-15
影响因子：
6.4
通讯作者：
Barbareschi, Mattia
中科院分区：
文献类型：
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作者：
Aldovini, Daniela;Demichelis, Francesca;Barbareschi, Mattia
目前可用的临床病理标准对晚期上皮性卵巢癌（EOC）患者的预后评估不完善。识别与肿瘤生物学相关的预后因素可能会改善这种评估。我们研究了黑色素瘤细胞粘附分子 (M-CAM) 在 EOC 中的预后意义。使用相同的抗体，通过蛋白提取物中的蛋白质印迹法和由 133 个连续切除的、经过充分表征的 EOC 样本生成的组织微阵列中的免疫组织化学来测试 M-CAM 表达。 Fisher 检验、Kaplan-Meier 方法和 Cox 比例风险分析用于将 M-CAM 表达与临床病理变量以及进展时间 (TTP) 和总生存期 (OS) 联系起来。体外生化分析显示，从正常细胞到恶性细胞，M-CAM 表达逐渐增加。通过免疫组织化学检测，MCAM 蛋白与晚期肿瘤分期、浆液性和未分化组织型、残留病变范围和 p53 积累显着相关。 M-CAM 的存在或不存在根据患者的 TTP（中位分别为 22 个月和 79 个月；对数秩 p = 0.001）和 OS（中位分别为 42 个月和 131 个月；对数秩 p = 0.0003）对患者进行了显着划分。在一线治疗后获得完全缓解的晚期患者亚组中，在多变量水平上，M-CAM 表达和无残留病灶与较短的 TTP 显着相关（分别为 p = 0.003、HR 5.25、95% CI 1.79-15.41 和 p = 0.011、HR 3.77、95% CI 1.36-10.49）。在同一患者亚组中，M-CAM 表达仍然是与 OS 显着相关的唯一参数（p = 0.005，HR 3.35，95% CI 1.42-6.88）。 M-CAM 是 EOC 早期复发和较差预后的标志。特别是，M-CAM 表达识别出一线治疗反应性患者的亚组，这些患者经历了严重的复发，从而有助于更好地选择可能受益于新的/替代治疗方式的患者。 (c) 2006 Wiley-Liss, Inc.
Currently available clinico-pathologic criteria provide an imperfect assessment of outcome for patients with advanced epithelial ovarian cancer (EOC). Identification of prognostic factors related to tumor biology might improve this assessment. We investigated the prognostic significance of the melanoma cell adhesion molecule (M-CAM) in EOC. Using the same antibody, M-CAM expression was tested by Western blotting in protein extracts and by immunohistochemestry in tissue microarrays generated from 133 consecutively resected, well characterized EOC samples. Fisher test, Kaplan-Meier method and Cox proportional hazards analysis were used to relate M-CAM expression to clinico-pathological variables and to time to progression (TTP) and overall survival (OS). In vitro biochemical analysis showed a progressively increased M-CAM expression from normal to malignant cells. MCAM protein, detected immunohistochemically, was significantly associated with advanced tumor stage, serous and undifferentiated histotype, extent of residual disease and p53 accumulation. Presence or absence of M-CAM significantly divided patients according to their TTP (median, 22 vs. 79 months, respectively; log-rank p = 0.001) and OS (median, 42 vs. 131 months, respectively; log-rank p = 0.0003). In the subgroup of advanced stage patients who achieved complete response after front-line treatment, M-CAM expression and absence of residual disease were significantly associated with shorter TTP (p = 0.003, HR 5.25, 95% CI 1.79-15.41 and p = 0.011, HR 3.77, 95% CI 1.36-10.49 respectively) at the multivariate level. In the same sub-group of patients, M-CAM expression remained the only parameter significantly associated with OS (p = 0.005, HR 3.35, 95% CI 1.42-6.88). M-CAM is a marker of early relapse and poorer outcome in EOC. In particular, M-CAM expression identifies a subgroup of front-line therapy-responding patients who undergo dramatic relapses, thus helping to better select patients who might benefit from new/alternative therapeutic modalities. (c) 2006 Wiley-Liss, Inc.