Greenson Joel K, Huang Shu-Chen, Herron Casey, Moreno Victor, Bonner Joseph D, Tomsho Lynn P, Ben-Izhak Ofer, Cohen Hector I, Trougouboff Phillip, Bejhar Jacob, Sova Yanina, Pinchev Mila, Rennert Gad, Gruber Stephen B
Department of Pathology, The University of Michigan Health System, Ann Arbor, MI 48109-0054, USA.
Am J Surg Pathol. 2009 Jan;33(1):126-33. doi: 10.1097/PAS.0b013e31817ec2b1.
Identification of microsatellite unstable (MSI-H) colorectal cancers (CRCs) is important not only for the identification of hereditary nonpolyposis colorectal cancer syndrome but also because MSI-H CRCs have a better prognosis and may respond differently to 5-fluorouracil-based chemotherapy. We present 2 nearly equivalent logistic regression models for clinical use that predict microsatellite instability based on the review of 1649 CRCs from patients of all ages collected in a population-based case control study in northern Israel. One hundred ninety-eight of these 1649 tumors demonstrated a high degree of microsatellite instability (12%). Multivariate analysis found that >2 tumor-infiltrating lymphocyte (TIL) cells per high-powered field, the lack of dirty necrosis, the presence of a Crohn-like reaction, right-sided location, any mucinous differentiation (mucinous or focally mucinous) and well or poor differentiation, and age less than 50 were all independent predictors of MSI-H. We developed 2 logistic regression models that differ only by the statistical approach used to analyze the number of TIL cells per high-powered field, where the slightly more accurate (and complex) model uses the log of the total number of TIL cells. The simpler clinical model uses a cut-off of 2>TIL cells per high-powered field. The accuracy of both models is high, with an 85.4% versus 85.0% probability of correctly classifying tumors as MSI-H. By employing the simpler model, pathologists can predict the likelihood of microsatellite instability by compiling the MSI probability score (Table 4 and Fig. 1) from simple histologic and clinical data available during sign-out. Our model shows that approximately 43% of CRCs have a MSI probability score of 1 or less and hence have little likelihood (<3%) of being MSI-H. Although this model is not perfect in predicting microsatellite instability, its use could improve the efficiency of expensive diagnostic testing.
鉴定微卫星不稳定（MSI-H）的结直肠癌（CRC）不仅对于遗传性非息肉病性结直肠癌综合征的诊断很重要，还因为MSI-H的CRC预后较好，并且对基于5-氟尿嘧啶的化疗可能有不同反应。我们提出了2个几乎等效的用于临床的逻辑回归模型，这些模型基于对以色列北部一项基于人群的病例对照研究中收集的1649例各年龄段CRC患者的回顾，来预测微卫星不稳定性。这1649例肿瘤中有198例表现出高度微卫星不稳定性（12%）。多变量分析发现，每高倍视野>2个肿瘤浸润淋巴细胞（TIL）细胞、无脏坏死、存在克罗恩样反应、右侧位置、任何黏液分化（黏液性或局灶性黏液性）以及高分化或低分化，以及年龄小于50岁，均为MSI-H的独立预测因素。我们开发了2个逻辑回归模型，它们的区别仅在于分析每高倍视野TIL细胞数量所采用的统计方法，其中稍更准确（且更复杂）的模型使用TIL细胞总数的对数。更简单的临床模型使用每高倍视野2>TIL细胞的临界值。两个模型的准确性都很高，将肿瘤正确分类为MSI-H的概率分别为85.4% 和85.0%。通过采用更简单的模型，病理学家可以根据签出时可用的简单组织学和临床数据编制MSI概率评分（表4和图1），来预测微卫星不稳定性的可能性。我们的模型显示，大约43%的CRC的MSI概率评分为1或更低，因此MSI-H的可能性很小（<3%）。尽管该模型在预测微卫星不稳定性方面并不完美，但其应用可以提高昂贵诊断检测的效率。
