Gulmann Christian, Grace Antoinette, Leader Mary, Butler David, Patchett Stephen, Kay Elaine
Department of Pathology, Beaumont Hospital and Royal College of Surgeons in Ireland, Dublin, Ireland.
Appl Immunohistochem Mol Morphol. 2003 Sep;11(3):230-7. doi: 10.1097/00129039-200309000-00005.
The aims of this study were (1) to compare protein expression of adenomatous polyposis coli (APC) gene, beta-catenin, and E-cadherin between proximal and distal gastric adenocarcinomas and (2) to investigate their use as markers of cancer risk in intestinal metaplasia (IM). The epidemiology of proximal (cardia and gastroesophageal junction) and distal (antrum and corpus) gastric carcinomas is strikingly different despite similar morphologies. Carcinoma of the distal stomach is decreasing in incidence, whereas proximal carcinomas are increasing in incidence more than any other cancer in the Western world. This phenomenon has so far not been satisfactorily explained. IM is a well-established precursor for adenocarcinoma in the distal stomach but less so in the proximal stomach. However, its specificity as a predictor of gastric carcinoma is very low. Abnormalities of APC, beta-catenin, and E-cadherin are implicated in carcinogenesis of the stomach and may show aberrant expression at early stages of the neoplastic process. This study evaluated their immunoprofiles in 3 groups: biopsies showing normal mucosa (n = 108), biopsies showing IM (n = 99), and gastric cancer resections (n = 117). In the last group, carcinoma and noninvolved mucosa were studied. All groups included material from both proximal and distal locations. The results of this study showed that there were no differences between proximal and distal locations with regard to APC, beta-catenin, or E-cadherin expression. In both locations, high normal expression rates for all 3 molecules were present in biopsies showing normal gastric mucosa or IM and noninvolved mucosa from gastric cancer resections. In carcinomas, there was a significant decrease in both APC and E-cadherin expression, whereas beta-catenin showed abnormal cytoplasmic and nuclear staining. Diffuse-type cancers showed significantly lower E-cadherin expression than intestinal types. Noninvolved mucosa from cancer resections showed normal APC, beta-catenin, and E-cadherin expression regardless of adjacent tumor type and whether the mucosa was morphologically normal or showed IM. In conclusion, proximal and distal gastric carcinomas show no differences in expression of APC, beta-catenin, or E-cadherin; thus, the observed abnormalities do not seem to contribute to the observed epidemiologic differences between these tumors. Because loss of APC, decreased E-cadherin, or abnormal beta-catenin expression did not occur in IM, even when associated with carcinoma these immunostains are unlikely to be of value in the assessment of malignant potential in IM.
（1）比较近端和远端胃癌中腺瘤性息肉病 coli（APC）基因、β-连环蛋白和 E-钙黏蛋白的蛋白表达；（2）研究它们作为肠化生（IM）中癌症风险标志物的用途。近端（贲门和胃食管交界处）和远端（胃窦和胃体）胃癌的流行病学情况显著不同，尽管形态相似。远端胃癌的发病率在下降，而在西方世界，近端胃癌的发病率比其他任何癌症上升得都要快。迄今为止，这一现象尚未得到令人满意的解释。IM 是远端胃癌公认的癌前病变，但在近端胃癌中则不然。然而，其作为胃癌预测指标的特异性非常低。APC、β-连环蛋白和 E-钙黏蛋白的异常与胃癌发生有关，并且可能在肿瘤形成过程的早期阶段出现异常表达。本研究评估了这三种蛋白在三组中的免疫表达情况：显示正常黏膜的活检样本（n = 108）、显示 IM 的活检样本（n = 99）以及胃癌切除术样本（n = 117）。在最后一组中，对癌组织和未受累黏膜进行了研究。所有组均包含来自近端和远端部位的样本。本研究结果显示，就 APC、β-连环蛋白或 E-钙黏蛋白的表达而言，近端和远端部位之间没有差异。在两个部位，显示正常胃黏膜或 IM 以及胃癌切除术中未受累黏膜的活检样本中，这三种分子的正常高表达率均存在。在癌组织中，APC 和 E-钙黏蛋白的表达均显著降低，而β-连环蛋白显示出异常的细胞质和细胞核染色。弥漫型癌的 E-钙黏蛋白表达显著低于肠型癌。无论相邻肿瘤类型如何，以及黏膜在形态上是否正常或显示 IM，癌症切除术中未受累黏膜的 APC、β-连环蛋白和 E-钙黏蛋白表达均正常。总之，近端和远端胃癌在 APC、β-连环蛋白或 E-钙黏蛋白的表达上没有差异；因此，观察到的异常似乎并未导致这些肿瘤之间观察到的流行病学差异。由于在 IM 中未出现 APC 缺失、E-钙黏蛋白减少或β-连环蛋白表达异常的情况，即使与癌相关，这些免疫染色在评估 IM 的恶性潜能方面也不太可能有价值。
