Department of Pathology and Laboratory Medicine.
Division of Biostatistics and Epidemiology, Weill Cornell Medicine, New York, NY.
Am J Surg Pathol. 2018 Dec;42(12):1686-1692. doi: 10.1097/PAS.0000000000001145.
Intestinal-type colorectal adenocarcinomas are graded based on extent of glandular differentiation, although mucinous, signet-ring cell, and solid cancers are, by convention, classified as high grade. Mismatch repair-deficient tumors frequently show high-grade histologic features, yet the World Health Organization classifies them as low grade to reflect their favorable prognosis compared with mismatch repair-proficient cancers. Although some mismatch repair-deficient colorectal cancers behave aggressively, few authors have identified features that predict their behavior. We performed this study to determine which histologic features, if any, predicted outcome among mismatch repair-deficient colorectal carcinomas. We identified 116 mismatch repair-deficient colorectal carcinomas, including 77 localized (stage I to II) and 39 advanced (stage III to IV) tumors, and evaluated them for extent of gland formation, extracellular mucin, signet-ring cell differentiation, solid growth, nuclear grade, tumor-infiltrating lymphocytes and tumor budding. Relationships between these features, pathologic stage, and disease-free survival were assessed. We found that high-grade mismatch repair-deficient tumors were more often of advanced stage than low-grade tumors (46% vs. 23%, P=0.01). Disease-free survival was inversely associated with the presence of a dominant high-grade component and tumor budding (P=0.01 and 0.04, respectively). Predominantly solid tumors, in particular, were significantly associated with decreased disease-free survival compared with low-grade tumors (P=0.001). Nuclear grade and tumor-infiltrating lymphocytes were not associated with pathologic stage or outcome. We conclude that low-grade mismatch repair-deficient carcinomas present at an earlier stage and pursue a more favorable course than those mostly composed of high-grade elements. These findings suggest that mismatch repair status should not supplant histologic grade in the assessment of colorectal carcinomas.
肠型结直肠腺癌根据腺体分化程度分级，尽管黏液性、印戒细胞和实性癌通常被归类为高级别。错配修复缺陷型肿瘤常表现出高级别组织学特征，但世界卫生组织将其归类为低级别，以反映其与错配修复功能良好型癌症相比预后较好。尽管一些错配修复缺陷型结直肠癌表现出侵袭性，但很少有作者确定了预测其行为的特征。我们进行这项研究是为了确定错配修复缺陷型结直肠腺癌中哪些组织学特征（如果有的话）可以预测结局。我们鉴定了 116 例错配修复缺陷型结直肠癌，包括 77 例局限性（I 期至 II 期）和 39 例晚期（III 期至 IV 期）肿瘤，并评估了它们的腺体形成程度、细胞外黏液、印戒细胞分化、实性生长、核级、肿瘤浸润淋巴细胞和肿瘤芽生。评估了这些特征与病理分期和无病生存之间的关系。我们发现，高级别错配修复缺陷型肿瘤比低级别肿瘤更常处于晚期（46%比 23%，P=0.01）。无病生存与存在优势高级别成分和肿瘤芽生呈负相关（分别为 P=0.01 和 0.04）。特别是主要为实性的肿瘤与低级别肿瘤相比，无病生存明显降低（P=0.001）。核级和肿瘤浸润淋巴细胞与病理分期或结局无关。我们得出结论，低级别错配修复缺陷型腺癌的分期较早，且预后比主要由高级别成分组成的腺癌更好。这些发现表明，在评估结直肠癌时，错配修复状态不应替代组织学分级。
