Clinical Research Center, Department of Pathology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Sweden.
Am J Surg Pathol. 2011 Sep;35(9):1391-9. doi: 10.1097/PAS.0b013e318225c3f0.
Identification of Lynch syndrome tumors is challenging. This relates particularly to MSH6-associated cases, which show reduced penetrance of colorectal cancer and a higher age at diagnosis. We recorded the clinical and morphologic features of 52 MSH6-associated colorectal cancers in comparison with MLH1/MSH2-mutant tumors and sporadic mismatch repair-deficient cancers. In the MSH6 subset, we confirmed a higher age (median, 56 y) at diagnosis and found a significantly larger proportion (25%) of rectal cancers. Presence of dirty necrosis was the sole histologic component that significantly differed between MSH6 and MLH1/MSH2 tumors. Compared with the sporadic mismatch repair-defective cohort, MSH6 cases had a lower prevalence of tumor-infiltrating lymphocytes and Crohn-like reactions. Mismatch repair defects were identified in 92% of MSH6 tumors, with high concordance between microsatellite instability and loss of immunohistochemical MSH6 expression. The remaining 8% showed a mismatch repair-stable phenotype, which suggests that analysis of additional tumors might be considered in families suspected of Lynch syndrome.
林奇综合征肿瘤的鉴定具有挑战性。这尤其与 MSH6 相关病例有关，这些病例的结直肠癌外显率降低，且诊断年龄较大。我们记录了 52 例 MSH6 相关结直肠癌的临床和形态学特征，并与 MLH1/MSH2 突变型肿瘤和散发性错配修复缺陷型癌症进行了比较。在 MSH6 亚组中，我们证实了诊断时年龄更高（中位数为 56 岁），并且发现直肠肿瘤的比例明显更高（25%）。存在脏坏死是 MSH6 和 MLH1/MSH2 肿瘤之间唯一显著不同的组织学成分。与散发性错配修复缺陷队列相比，MSH6 病例中肿瘤浸润淋巴细胞和克罗恩样反应的发生率较低。92%的 MSH6 肿瘤存在错配修复缺陷，微卫星不稳定性和免疫组化 MSH6 表达缺失之间具有高度一致性。其余 8%表现出错配修复稳定表型，这表明在疑似林奇综合征的家族中可能需要考虑分析其他肿瘤。
