Signet Ring Cell Colorectal Carcinoma A Distinct Subset of Mucin-poor Microsatellite-stable Signet Ring Cell Carcinoma Associated With Dismal Prognosis
Signet Ring Cell Colorectal Carcinoma A Distinct Subset of Mucin-poor Microsatellite-stable Signet Ring Cell Carcinoma Associated With Dismal Prognosis
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DOI：
10.1097/pas.0b013e3182851e2b
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发表时间：
2013-07-01
影响因子：
5.6
通讯作者：
Pai, Reetesh K.
中科院分区：
文献类型：
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作者：
Hartman, Douglas J.;Nikiforova, Marina N.;Pai, Reetesh K.
我们评估了一系列连续的印戒细胞结直肠癌，试图将浸润的组织病理学模式与分子改变和预后联系起来。在2002年至2012年手术切除的4760例原发性结直肠癌中，53例（1%）由>50%的印戒细胞组成。在53例印戒细胞癌中，40例（75%）由>50%的细胞外粘蛋白组成，印戒细胞漂浮在粘蛋白池中，并被细分为富含粘蛋白的印戒细胞癌。13例（25%）癌的特征为弥漫性浸润癌，伴有极少量或无细胞外粘蛋白，并被细分为粘蛋白缺乏的印戒细胞癌。所有13例粘蛋白缺乏的印戒细胞癌均为III期或IV期，而许多粘蛋白丰富的印戒细胞癌为I期或II期（17例）（P = 0.005）。与富含粘蛋白的肿瘤相比，缺乏粘蛋白的印戒细胞癌更常表现出不良的组织学特征，如淋巴管浸润（13/13，100% vs. 22/40，55%; P = 0.002），静脉侵犯（6/13，46% vs. 3/40，8%; P = 0.004）和神经周围浸润（11/13，85% vs. 9/40，23%; P = 0.0001）。53例印戒细胞癌中有23例（43%）表现出高水平的微卫星不稳定性（MSI-H）。23例MSI-H印戒细胞癌中有22例（96%）富含粘蛋白;只有1例MSI-H印戒细胞癌粘蛋白缺乏（P = 0.0033）。与富含粘蛋白的印戒细胞癌相比，粘蛋白缺乏的印戒细胞癌的总体生存率和无复发生存率显著降低（分别为P = 0.0035和0.0001），即使调整了肿瘤分期。与富含粘蛋白的印戒细胞癌（5/40，12.5%）相比，缺乏粘蛋白的印戒细胞癌有更高的腹膜播散倾向（5/13，38%），尽管这在统计学上不显著（P = 0.052）。最后，MSI-H和微卫星稳定的印戒细胞癌具有相似的总体和无复发生存率（分别为P = 0.2266和0.1055），即使调整肿瘤分期。总之，我们确定了一个独特的印戒细胞结直肠癌的亚群，具有弥漫性浸润和最小或无细胞外粘蛋白（粘蛋白缺乏印戒细胞癌），缺乏MSI-H，预后不良，临床病程侵袭性强，常伴有腹膜播散。此外，我们的研究结果证实，MSI不影响生存在结直肠印戒细胞癌。
We evaluated a consecutive series of signet ring cell colorectal carcinomas in an attempt to correlate the histopathologic pattern of infiltration with molecular alterations and prognosis. Of the 4760 primary colorectal carcinomas surgically resected between the years 2002 and 2012, 53 (1%) were composed of >50% signet ring cells. Of the 53 signet ring cell carcinomas, 40 (75%) were composed of >50% extracellular mucin with signet ring cells floating within pools of mucin and were subclassified as mucin-rich signet ring cell carcinomas. Thirteen (25%) carcinomas were characterized by diffusely infiltrating carcinomas with minimal to no extracellular mucin and were subclassified as mucin-poor signet ring cell carcinomas. All 13 mucin-poor signet ring cell carcinomas were either stage III or IV, whereas many cases of mucin-rich signet ring cell carcinoma were stage I or II (17 cases) (P = 0.005). Compared with mucin-rich tumors, mucin-poor signet ring cell carcinomas more frequently demonstrated adverse histologic features such as lymphatic invasion (13/13, 100% vs. 22/40, 55%; P = 0.002), venous invasion (6/13, 46% vs. 3/40, 8%; P = 0.004), and perineural invasion (11/13, 85% vs. 9/40, 23%; P = 0.0001). Twenty-three of 53 (43%) signet ring cell carcinomas demonstrated high levels of microsatellite instability (MSI-H). Twenty-two of 23 (96%) MSI-H signet ring cell carcinomas were mucin rich; only 1 MSI-H signet ring carcinoma was mucin poor (P = 0.0033). Mucin-poor signet ring cell carcinoma had significantly reduced overall and recurrence-free survival compared with mucin-rich signet ring cell carcinomas (P = 0.0035 and 0.0001, respectively), even when adjusting for tumor stage. Mucin-poor signet ring cell carcinoma had a higher propensity for peritoneal dissemination (5/13, 38%) compared with mucin-rich signet ring cell carcinoma (5/40, 12.5%), although this was not statistically significant (P = 0.052). Finally, MSI-H and microsatellite-stable signet ring cell carcinomas had similar overall and recurrence-free survival (P = 0.2266 and 0.1055, respectively), even when adjusting for tumor stage. In conclusion, we identified a unique subset of signet ring cell colorectal carcinoma with diffuse infiltration and minimal to no extracellular mucin (mucin-poor signet ring cell carcinoma), which lacks MSI-H and has a dismal prognosis with an aggressive clinical course often with peritoneal dissemination. Further, our results confirm that MSI does not affect survival in colorectal signet ring cell carcinomas.