TRIM72 Immunohistochemical Expression Can Predict Relapse in Colorectal Carcinoma
TRIM72 Immunohistochemical Expression Can Predict Relapse in Colorectal Carcinoma
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DOI：
10.1007/s12253-019-00629-w
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发表时间：
2020-04-01
影响因子：
2.8
通讯作者：
Cebrian, A.
中科院分区：
文献类型：
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作者：
Fernandez-Acenero, M. J.;Cruz, M.;Cebrian, A.
大肠腺癌是人类最常见的肿瘤之一，尽管最近对这种疾病的病理生理学和分子基础有了深入的了解，但晚期和转移性病例的死亡率仍然很高。大多数指南建议对涉及淋巴结的肿瘤进行辅助化疗，但不适用于局部I期或II期疾病的患者。然而，众所周知，大约20%的II期结直肠癌患者最终复发，主要是远处或腹膜受累，预后不良。重要的是要预测哪些患者复发风险增加，以指导潜在的辅助治疗在这种有争议的情况下使用。在这个意义上，只有微卫星稳定性已被提议作为一个预测工具，在一些指南。TRIM 72是一种泛素连接酶，参与细胞膜修复机制，与胰岛素抵抗有关。它在结肠癌中的潜在作用最近被提出。本研究的目的是确定TRIM 72免疫组化表达在II期结肠癌中的潜在预测价值。我们回顾性分析了2006年至2012年期间在马德里（西班牙）一家大型三级医院进行根治性手术的95例II期结肠微卫星稳定型癌患者。所有患者均未接受辅助化疗。我们回顾了组织病理学切片，并构建了三个代表性区域的组织微阵列（TMA），以进行TRIM 72的免疫组织化学染色。在我们的系列中，30例患者（31.7%）在中位随访17.5个月后复发。TRIM 72在肿瘤中的免疫组化表达的缺乏与复发显著且独立相关。Chen等人的最近报道显示，TRIM 72可以在血浆中测量用于结肠癌检测，作为CEA或CA 19.9的替代，在癌症患者中具有较低水平。我们的报告是第一个表明TRIM 72的免疫组化表达较低预测II期结肠癌复发的报告。我们认为这种预测影响可能与其作为许多信号通路（PI 3 K-AKT，ERK）中的中央调节器的关键作用有关。作为一种泛素连接酶，缺乏TRIM 72可能会增加几种潜在致癌分子的水平，因此导致更具侵袭性的表型。化疗是否能改变这一预后不良人群的临床表现还有待证实。我们建议TRIM 72免疫组化分析作为一个潜在的工具，以预测复发风险的第二阶段结肠癌患者。我们的研究结果应该在更大的系列中得到证实，但可能为这一早期患者组的管理策略改进开辟道路。
Large bowel adenocarcinoma is one of the most frequent human neoplasms and despite recent insights into the pathophysiology and molecular basis of this disease, mortality remains high in advanced and metastatic cases. Most guidelines recommend adjuvant chemotherapy for tumours involving lymph nodes, but not for patients with localized stage I or II disease. However, it is well known that approximately 20% of stage II colorectal carcinoma patients eventually recur, mainly with distant or peritoneal involvement and show bad prognosis. It would be important to predict which patients are at increased risk of recurrence to guide potential adjuvant therapy use in this controversial setting. In this sense, only microsatellite stability has been proposed as a predictive tool in some guidelines. The tripartite motif family protein 72 (TRIM72) is a ubiquitin ligase, involved in the cell membrane repair machinery and known to be associated to insulin resistance. Its potential role in colon cancer has recently been proposed. The aim of this study is to determine the potential predictive value of TRIM72 immunohistochemical expression in stage II colon carcinoma. We have retrospectively reviewed a series of 95 patients with stage II colon microsatellite stable carcinomas operated with a curative intent at a single large tertiary hospital in Madrid (Spain) between 2006 and 2012. None of the patients received adjuvant chemotherapy. We reviewed the histopathological slides and constructed a tissue microarray (TMA) of three representative areas to perform immunohistochemical staining for TRIM72. In our series 30 patients (31.7%) recurred after a median follow-up of 17.5 months. Lack of immunohistochemical expression of TRIM72 in the tumor was significantly and independently associated to recurrence. A recent report by Chen et al. has shown that TRIM72 can be measured in plasma for colon carcinoma detection as an alternative to CEA or CA19.9, with lower levels in patients with carcinoma. Our report is the first one to show that lower immunohistochemical expression of TRIM72 predicts recurrence in colon stage II carcinoma. We feel this predictive influence can be related to its crucial role as a central regulator in many signaling pathways (PI3K-AKT, ERK). As an ubiquitin ligase, the lack of TRIM72 could increase the levels of several potential oncogenic molecules and therefore lead to a more aggressive phenotype. It remains to be shown whether chemotherapy could change the clinical behaviour of this bad prognosis group. We propose TRIM72 immunohistochemical analysis as a potential tool to predict recurrence risk in stage II colon carcinoma patients. Our results should be confirmed in larger series, but could open the way to management strategies refinement in this early stage group of patients.