Loss of MUC2 expression predicts disease recurrence and poor outcome in colorectal carcinoma

Loss of MUC2 expression predicts disease recurrence and poor outcome in colorectal carcinoma
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DOI:
10.1007/s13277-012-0588-8
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发表时间:
2013-04-01
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影响因子:
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通讯作者:
Pyrhonen, Seppo
Pyrhonen, Seppo
中科院分区:
其他
文献类型:
--
作者:
Elzagheid, Adam;Emaetig, Fatma;Pyrhonen, Seppo

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临床分期和术后组织学分级一直是预测结直肠癌预后和制定辅助治疗方案的“金标准”。随着分子标记物的发展,在分子水平上对肿瘤进行定性已经成为可能。这对于II期和III期CRC是重要的,其中临床病理学特征不能准确预测异质性,例如,肿瘤对辅助治疗的反应。在本研究中,使用1981-1990年期间在芬兰图尔库大学医院接受治疗的141例I、II、III或IV期CRC患者的存档样本(作为微阵列块),通过免疫组织化学分析MUC 2表达。总的来说,49.7%的肿瘤对MUC 2呈阳性。MUC 2的表达与年龄(P < 0.499)、肿瘤浸润深度(P < 0.127)、肿瘤分期(P < 0.470)、组织学分级(P < 0.706)、淋巴结转移(P < 0.854)和肿瘤转移(P < 0.586)均无明显相关性。MUC 2表达缺失与肿瘤复发(P < 0.031)、肿瘤定位(P < 0.048)及性别(P < 0.085)有显著相关性。在单变量(Kaplan-Meier)生存分析中,MUC 2阳性显著预测较长的无病生存期(DFS)和疾病特异性生存期(DSS)。然而,在多变量(考克斯)生存分析中,MUC 2失去了作为DFS和DSS的独立预测因子的能力。我们的研究结果暗示MUC 2表达在预测结直肠癌复发和长期生存中的价值。
Clinical staging and histological grading after surgery have been the "gold standard" for predicting prognosis and planning for adjuvant therapy of colorectal cancer (CRC). With the recent development of molecular markers, it has become possible to characterize tumors at the molecular level. This is important for stage II and III CRCs, in which clinicopathological features do not accurately predict heterogeneity, e.g., in their tumor response to adjuvant therapy. In the present study, archival samples from 141 patients with stage I, II, III, or IV CRC treated during 1981-1990 at Turku University Hospital (Finland) were used (as microarray blocks) to analyze MUC2 expression by immunohistochemistry. Altogether, 49.7 % of all tumors were positive for MUC2. There was no significant correlation between MUC2 expression and age (P < 0.499), tumor invasion (P < 0.127), tumor staging (P < 0.470), histological grade (P < 0.706), lymph node involvement (P < 0.854), or tumor metastasis (P < 0.586). However, loss of MUC2 expression was significantly associated with disease recurrence (P < 0.031), tumor localization (P < 0.048), and with borderline significance with gender (P < 0.085). In univariate (Kaplan-Meier) survival analysis, positive MUC2 significantly predicted longer disease-free survival (DFS) and disease-specific survival (DSS) as well. However, in multivariate (Cox) survival analysis, MUC2 lost its power as an independent predictor of DFS and DSS. Our results implicate the value of MUC2 expression in predicting disease recurrence and long-term survival in CRC.