Guner Gunes, Isik Aynur, Karabulut Erdem, Gedikoglu Gokhan, Sokmensuer Cenk, Akyol Aytekin
Departments of Pathology.
Transgenic Animal Technologies Research and Application Center, Hacettepe University, Ankara, Turkey.
Appl Immunohistochem Mol Morphol. 2018 Nov/Dec;26(10):e107-e115. doi: 10.1097/PAI.0000000000000618.
Gastric carcinoma management requires adjustments answering their genetic and morphologic heterogeneity. We aim to assess the expression and significance of a myriad of biomarkers (p53, MLH1, MSH2, PMS2, MSH6, Epstein-Barr encoding region-RNA, c-erbB2, E-cadherin, CEA, chromogranin, Ki-67, CDX2, presenilin-1, cathepsin E, MUC5AC, cyclin-dependent kinase 1) in 117 gastric carcinomas, which we have morphologically subclassified with a simple algorithm. Immunohistochemical stains were applied to 3 tissue microarrays of primary gastric carcinomas (n=117) obtained from resection specimens of untreated patients. These cases represented the morphologic subgroups that emerged from a reclassification attempt carried out according to the predominant (>50%) morphologic component they contained (adenocarcinoma, diffuse infiltrative carcinoma, mucinous carcinoma) and "mixed" carcinoma if none predominated. Cases with unusual morphology were assigned to a "special subtypes" group ("rare" tumors). Correlation of overall survival and staining patterns was carried out. Adenocarcinomas comprised 43.6% (n=51), diffuse infiltrative carcinomas 28.2% (n=33), mucinous carcinomas 6% (n=7), mixed carcinomas 6%, and "rare/other" carcinomas 16.2% (n=19) of the 117 muscle-invasive carcinoma cases. High tumor stage was associated with worse overall survival at multivariate analysis (P=0.000, log-rank). Higher cathepsin E and cyclin-dependent kinase 1 expression was associated with worse overall survival on univariate analysis (log-rank; P=0.050 and 0.001, respectively). Mismatch repair defects were seen in adenocarcinomas and "rare" tumors with MLH1 silencing. These above-mentioned points can lead to the differentiation of metabolic and phenotypic features per gastric carcinoma subtype and may help design targeted approaches.
胃癌的治疗需要根据其基因和形态学异质性进行调整。我们旨在评估117例胃癌中多种生物标志物（p53、MLH1、MSH2、PMS2、MSH6、爱泼斯坦-巴尔编码区RNA、c-erbB2、E-钙黏蛋白、癌胚抗原、嗜铬粒蛋白、Ki-67、CDX2、早老素-1、组织蛋白酶E、MUC5AC、细胞周期蛋白依赖性激酶1）的表达及其意义，我们已使用一种简单算法对这些胃癌进行了形态学亚分类。免疫组织化学染色应用于从未经治疗患者的切除标本中获取的3个原发性胃癌组织微阵列（n = 117）。这些病例代表了根据其所含主要（>50%）形态学成分（腺癌、弥漫浸润性癌、黏液癌）重新分类尝试中出现的形态学亚组，若没有主要成分，则为“混合”癌。形态异常的病例被归入“特殊亚型”组（“罕见”肿瘤）。进行了总生存期与染色模式的相关性分析。在117例肌层浸润性癌病例中，腺癌占43.6%（n = 51），弥漫浸润性癌占28.2%（n = 33），黏液癌占6%（n = 7），混合癌占6%，“罕见/其他”癌占16.2%（n = 19）。多变量分析显示高肿瘤分期与较差的总生存期相关（P = 0.000，对数秩检验）。单变量分析显示较高的组织蛋白酶E和细胞周期蛋白依赖性激酶1表达与较差的总生存期相关（对数秩检验；P分别为0.050和0.001）。在MLH1沉默的腺癌和“罕见”肿瘤中发现错配修复缺陷。上述要点可导致区分每种胃癌亚型的代谢和表型特征，并可能有助于设计靶向治疗方法。
