Clinicopathologic and Molecular Profiles of Microsatellite Unstable Barrett Esophagus-associated Adenocarcinoma
Clinicopathologic and Molecular Profiles of Microsatellite Unstable Barrett Esophagus-associated Adenocarcinoma
复制标题
DOI：
10.1097/pas.0b013e31820f18a2
复制
发表时间：
2011-05-01
影响因子：
5.6
通讯作者：
Mino-Kenudson, Mari
中科院分区：
文献类型：
--
作者：
Farris, Alton B., III;Demicco, Elizabeth G.;Mino-Kenudson, Mari
微卫星不稳定性（MSI）已在各种肿瘤中报道，结肠癌为原型。然而，关于Barrett食管（BE）相关腺癌的MSI知之甚少。因此，本研究的目的是比较有和没有MSI的BE相关腺癌的临床病理和分子特征。研究队列包括76例BE相关腺癌患者（66例男性，10例女性），平均年龄为65.1岁。对MLH 1、MSH 2、MSH 6、PMS 2和CD 3进行免疫组织化学（IHC），并对EB病毒编码的RNA进行原位杂交。5例（6.6%）经免疫组化检测MLH 1和PMS 2表达缺失;其中5例经聚合酶链反应检测显示高水平MSI（MSI-H），4例显示hMLH 1启动子甲基化。在组织学上，MSI-H肿瘤是异质性的，包括具有肿瘤浸润淋巴细胞的常规腺癌（n = 1）、髓样癌（n = 2）、印戒细胞（n = 1）以及印戒细胞和粘液成分（n = 1）。与通过IHC检测MSI阴性的肿瘤相比，伴有MSI-H的BE相关腺癌与患者年龄较大（P = 0.0060）、淋巴管浸润（P = 0.027）和肿瘤浸润淋巴细胞数量显著增加（P < 0.0001）相关。然而，两组之间的总生存期无统计学差异（P = 0.285）。总之，MSI-H在BE相关腺癌中并不常见，但与散发性微卫星不稳定结直肠癌的临床病理特征非常相似。鉴于越来越多的证据表明氟尿嘧啶辅助治疗结肠癌缺乏益处，因此在BE相关腺癌中鉴定MSI-H可能很重要。
Microsatellite instability (MSI) has been reported in various tumors, with colon cancer as the prototype. However, little is known about MSI in Barrett esophagus (BE)-associated adenocarcinoma. Thus, the aim of this study was to compare the clinicopathologic and molecular features of BE-associated adenocarcinomas with and without MSI. The study cohort consisted of 76 patients with BE-associated adenocarcinomas (66 male, 10 female), with a mean age of 65.1 years. Immunohistochemistry (IHC) for MLH1, MSH2, MSH6, PMS2, and CD3 and in situ hybridization for Epstein-Barr virus-encoded RNA were performed. MLH1 and PMS2 expression was lost by IHC in 5 cases (6.6%); of these, 5 showed high-level MSI (MSI-H) by polymerase chain reaction assay, and 4 showed hMLH1 promoter methylation. Histologically, tumors with MSI-H were heterogenous and included conventional adenocarcinomas with tumor-infiltrating lymphocytes (n = 1), medullary carcinoma (n = 2), signet ring cells (n = 1), and signet ring cell and mucinous components (n = 1). Compared with tumors negative for MSI by IHC, BE-associated adenocarcinomas with MSI-H were associated with older patient age (P = 0.0060), lymphovascular invasion (P = 0.027), and significantly larger numbers of tumor-infiltrating lymphocytes (P < 0.0001). However, there was no statistical difference in overall survival between the 2 groups (P = 0.285). In conclusion, MSI-H is uncommon in BE-associated adenocarcinomas, but is associated with clinicopathologic features fairly similar to sporadic microsatellite unstable colorectal cancers. Given the growing evidence that indicates lack of benefits from adjuvant therapy with fluorouracil in the colonic counterpart, it may be important to identify MSI-H in BE-associated adenocarcinomas.