Differences of the Clinicopathological Features and Expression of Mismatch Repair Proteins between Colorectal Cancer Patients Who Fulfilled with the Amsterdam-II Criteria Completely and Lack Only One

完全符合阿姆斯特丹－II標準或僅缺少一個標準之結直腸癌病人的臨床病理特徵及錯配修復蛋白表現之差異

江支銘(Jy-Ming Chiang) ； 陳澤卿(Tse-Ching Chen) ； 蔣昇甫(Sum-Fu Chiang) ； 游正府(Jeng-Fu You) ； 洪欣園(Hsin-Yun Huang)

《中華民國大腸直腸外科醫學會雜誌》 30卷2期 (2019/06) Pp. 56-69

https://doi.org/10.6312/SCRSTW.201906_30(2).10726

摘要

Purpose. Hereditary nonpolyposis colorectal cancer (HNPCC) patients were reported with clinicopathological characteristics. To compare the clinicopathological characteristics of patients who satisfied the Amsterdam II criteria (A-II C) or lack one criterion alone (HNPCC-like). Methods. Immunohistochemistry was used to detect mismatch repair (MMR) gene expression. Cox proportional hazards model was used to investigate the effect of the A-II C and MMR status on survival and clinicpathological factors. Results. We retrospectively evaluated patients who satisfied the A-II C or lack one criterion alone over a period of 14 years. 380 CRC patients were collected including 177 patients with HNPCC and 203 HNPCC-like cases (lacking one A-II criterion) were analyzed. Overall, 63.3% of the HNPCC patients and 16.3% of the HNPCC-like cases demonstrated loss of at least one MMR protein. MMR-deficient (dMMR) patients had larger tumors (28 cm^2 vs. 18 cm^2, p ＜ 0.0001), deeper (T4) tumor invasion (40.7% vs. 29.0%, p ＜ 0.0173), lower rates of lymph node involvement (N0, 31.0% vs. 48.5%, p = 0.0034), and fewer distant metastases (M0, 8.3% vs. 15.3%, p = 0.0447) than MMR-proficient (pMMR) patients. The dMMR/HNPCClike subgroup also had significantly more male patients (72.7% vs. 43.8%, p = 0.0034) and a higher rate of poor differentiation (42.4% vs. 22.9%, p ＜ 0.028) than the dMMR/HNPCC subgroup. Significantly different rates of developing metachrous CRC were observed, ranging from lowest 3.28 (pMMR/HNPCC-like), 6.18 (pMMR/HNPCC), 20.57 (dMMR/HNPCC), to highest 37.78 person-years. Conclusion. We reported distinguishing features related to the subgroups of dMMR/HNPCC-like patients, including male predominance and an extremely high rate of poor differentiation. In addition, risk of developing metachronous CRC might be further classified by combining family history and MMR status.

關鍵字

Amsterdam II criteria ； Detect mismatch repair gene expression ； Metachronous CRC ； Male ； Poor differentiation

並列摘要

目的：遺傳性非息肉性結直腸癌（HNPCC）患者被報導具有臨床病理學特徵。本研究比較滿足阿姆斯特丹II標準（A-II C）或僅缺乏一個標準的患者（HNPCC-like）的臨床病理特徵。方法：利用免疫組織化學用於檢測錯配修復（MMR）基因表現。Cox比例風險模型用於研究A-II C和MMR狀態對生存和臨床病理因素的影響。結果：我們回顧性評估共380例大腸直腸癌患者，包括177例HNPCC患者和203例類似HNPCC樣病例（缺乏一種A-II標準）。總體而言，63.3％的HNPCC患者和16.3％的HNPCC樣病例表現出至少一種MMR蛋白的喪失。與MMR-正常（pMMR）患者相比，MMR缺陷（dMMR）患者具有腫瘤較大（28 cm^2vs.18 cm^2，p＜0.0001），腫瘤浸潤較深（T4）（40.7% vs. 29.0%，p＜0.0173)，淋巴結轉移率較低（N0）（31.0% vs. 48.5%，p＝0.0034），及遠處轉移（M0，8.3%對15.3%，p＝0.0447）較少。與dMMR／HNPCC亞組相比，dMMR／類似HNPCC亞組的男性患者（72.7% vs. 43.8%，p＝0.0034）顯著更多，腫瘤分化差（42.4％vs.22.9％，p＜0.028）更高。並且觀察到顯著不同的發展中有限的CRC的發生率，從最低3.28（pMMR／類似HNPCC），6.18（pMMR／HNPCC），20.57（dMMR／HNPCC）到最高37.78人年（dMMR／類似HNPCC）。結論：我們報告了dMMR／HNPCC樣患者亞組相關的顯著特徵，包括男性佔優勢，極低分化率和發生異時CRC的風險。因此，經由結合家族史和MMR狀態，可以進一步對發生異時性結直腸癌的風險進行分類。

並列關鍵字

阿姆斯特丹－II標準 ； 錯配修復蛋白表現缺陷 ； 異時性結直腸癌 ； 分化不良 ； 男性

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