A novel logistic model based on clinicopathological features predicts microsatellite instability in colorectal carcinomas
A novel logistic model based on clinicopathological features predicts microsatellite instability in colorectal carcinomas
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DOI：
10.1097/01.pas.0000177800.65959.48
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发表时间：
2005-12-01
影响因子：
--
通讯作者：
Puig, X
中科院分区：
文献类型：
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作者：
Colomer, A;Erill, N;Puig, X
据报道，高频微卫星不稳定性与结直肠腺癌的良好预后相关。然而，评估微卫星不稳定性 (MIN) 的方法基于遗传测定，并不适合大多数组织病理学实验室。本研究的目的是开发一个基于表型特征预测结直肠癌 MIN 状态的模型。按照预定标准对 204 名原发性结肠癌患者的临床病理学特征进行了回顾性评价。通过测试一组 11 个微卫星标记，对从福尔马林固定、石蜡包埋的标本切片中提取的 DNA 进行 MIN 状态的遗传评估。 Logistic 回归分析生成了一种数学工具，能够识别显示 MIN 状态的结直肠肿瘤，灵敏度为 77.8%，特异性为 96.8%。与不稳定相关的特征包括病变的近端位置、实体和/或粘液分化的发生、筛状结构的缺失、瘤周克罗恩样反应的存在、扩张的生长模式、高Ki67增殖指数和p53阴性表型。该方法预测结直肠癌中的微卫星不稳定性，总体分配准确度为 95.1%，阴性预测值为 97.8%。在常规组织病理学研究中应用该工具可以改善结直肠癌患者的治疗，特别是那些患有 II 期和 III 期疾病的患者。它还将有助于确定可能受益于辅助化疗的患者子集。
High-frequency microsatellite instability has been reported to be associated with good prognosis in colorectal adenocarcinoma. However, methods to assess microsatellite instability (MIN) are based on genetic assays and are not ideally suited to most histopathology laboratories. The aim of the present study was to develop a model for prediction of MIN status in colorectal cancer based on phenotypic characteristics. Clinicopathological features of a cohort of 204 patients with primary colon cancer were retrospectively reviewed following predetermined criteria. Genetic assessment of MIN status was performed on DNA extracted from sections of formalin-fixed, paraffinembedded specimens by testing a panel of 11 microsatellite markers. Logistic regression analysis generated a mathematical tool capable of identifying colorectal tumors displaying MIN status with a sensitivity of 77.8% and a specificity of 96.8%. Features associated with instability included the proximal location of the lesions, occurrence of solid and/or mucinous differentiation, absence of cribriform struclures, presence of peritumoral Crohn-like reaction, expansive growth pattern, high Ki67 proliferative index, and p53-negative phenotype. This approach predicts microsatellite instability in colorectal carcinoma with an overall assigned accuracy of 95.1% and a negative predictive value of 97.8%. Implementation of this tool to routine histopathological studies could improve the management of patients with colorectal cancer, especially those presenting with stage II and III of the disease. It will also assist in identifying a subset of patients likely to benefit from adjuvant chemotherapy.