Nashville VA Medical Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Hum Pathol. 2013 May;44(5):734-42. doi: 10.1016/j.humpath.2012.07.017. Epub 2012 Oct 16.
Upper gastrointestinal neoplasia in the esophagus, stomach, and pancreas is associated with the formation of preneoplastic metaplasias. We have previously reported the up-regulation of human epididymis protein 4 (HE4) in all metaplasias in the stomach of humans and mice. We have now sought to evaluate the expression of HE4 in metaplasias/preneoplastic precursors and cancers of the human stomach, pancreas, and esophagus. Tissue microarrays for gastric cancers, pancreatic cancers, and esophageal adenocarcinoma were stained with antibodies against HE4. Immunostaining was quantified by digital imaging, and the results were evaluated to assess the expression in metaplasias, the expression in cancer pathological subtypes, and the effects of expression on survival in patients with cancer. In patients with gastric cancer from Korea, HE4 was detected in 74% of intestinal and 90% of diffuse cancers, whereas in a gastric cancer cohort from Johns Hopkins, HE4 was detected in 74% of intestinal-type and 92% of diffuse cancers. Nevertheless, in both cohorts, there was no impact of HE4 expression on overall survival. In the esophagus, we observed the expression of HE4 in scattered endocrine cells within Barrett esophagus samples, but Barrett columnar metaplasias and HE4 were detected in only 2% of esophageal adenocarcinomas. Finally, in the pancreas, HE4 expression was not observed in pancreatic intraepithelial neoplasia lesions, but 46.8% of pancreatic adenocarcinomas expressed HE4. Still, we did not observe any influence of HE4 expression on survival. The results suggest that HE4 is up-regulated during gastric and pancreatic carcinogenesis.
食管、胃和胰腺的上消化道肿瘤与癌前性化生的形成有关。我们之前曾报道过，人附睾蛋白 4（HE4）在人类和小鼠胃的所有化生中均上调。现在，我们试图评估 HE4 在人类胃、胰腺和食管的化生/癌前前体和癌症中的表达。使用针对 HE4 的抗体对胃癌、胰腺癌和食管腺癌的组织微阵列进行染色。通过数字成像对免疫染色进行定量，并评估结果以评估在化生中的表达、在癌症病理亚型中的表达以及表达对癌症患者生存的影响。在来自韩国的胃癌患者中，HE4 在 74%的肠型和 90%的弥漫型癌症中被检测到，而在约翰霍普金斯的胃癌队列中，HE4 在 74%的肠型和 92%的弥漫型癌症中被检测到。然而，在这两个队列中，HE4 的表达均与总生存率无关。在食管中，我们观察到在 Barrett 食管样本中的散在内分泌细胞中表达 HE4，但 Barrett 柱状化生和 HE4 仅在 2%的食管腺癌中被检测到。最后，在胰腺中，HE4 表达未在胰腺上皮内瘤变病变中被检测到，但 46.8%的胰腺腺癌表达 HE4。尽管如此，我们没有观察到 HE4 表达对生存的任何影响。结果表明，HE4 在胃和胰腺发生癌变过程中上调。
