Department of Cancer Research and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
Department of Pathology, St Olav's Hospital-Trondheim University Hospital, Trondheim, Norway.
Horm Cancer. 2018 Feb;9(1):40-54. doi: 10.1007/s12672-017-0311-8. Epub 2017 Oct 4.
Gastric cancer is an important disease due to its high mortality. Despite the decline in frequency, most cases are discovered late in its course, and most of the cancer patients die within a few years of diagnosis. In addition to Helicobacter pylori gastritis, gastrin is considered an important factor in the development of this disease, and thus, cholecystokinin-B receptor (CCKBR) becomes of interest. The aim of our study was to explore whether CCKBR is expressed in stomach cancers. Thirty-seven tumors from 19 men and 18 women diagnosed with either adenocarcinoma or neuroendocrine neoplasm (NENs) were included in this study. The tumors were classified into 29 adenocarcinomas and eight NENs. Immunohistochemistry with antibodies against chromogranin A (CgA), synaptophysin and CCKBR, and in situ hybridization with probes against CgA, CCKBR and histidine decarboxylase were used to further explore these tumors. Thirty-three (89%) of the tumors expressed CCKBR protein, whereas only 20 (54%) of all tumors expressed CCKBR mRNA. Of the 20 tumors expressing CCKBR mRNA, eight were NENs and 12 were adenocarcinoma. The highest amount of CCKBR was expressed in NEN. Interestingly, a high degree of co-expression of CCKBR and CgA was observed when the two markers were examined together with in situ hybridization. In conclusion, we found that all eight NENs expressed CCKBR and neuroendocrine markers in a majority of tumor cells. The same markers were also expressed in a proportion of adenocarcinomas supporting the view that gastrin is important in the development of gastric cancer.
胃癌是一种重要的疾病，因为其死亡率很高。尽管发病率有所下降，但大多数病例在病程晚期才被发现，大多数癌症患者在诊断后几年内死亡。除了幽门螺杆菌胃炎外，胃泌素被认为是这种疾病发展的一个重要因素，因此，胆囊收缩素 B 受体（CCKBR）成为研究的焦点。我们的研究目的是探讨 CCKBR 是否在胃癌中表达。本研究纳入了 19 名男性和 18 名女性的 37 例肿瘤，这些患者被诊断为腺癌或神经内分泌肿瘤（NEN）。这些肿瘤分为 29 例腺癌和 8 例 NEN。使用针对嗜铬粒蛋白 A（CgA）、突触素和 CCKBR 的抗体进行免疫组织化学染色，以及针对 CgA、CCKBR 和组氨酸脱羧酶的探针进行原位杂交，以进一步探索这些肿瘤。33 例（89%）肿瘤表达 CCKBR 蛋白，而所有肿瘤中只有 20 例（54%）表达 CCKBR mRNA。在表达 CCKBR mRNA 的 20 例肿瘤中，有 8 例为 NEN，12 例为腺癌。NEN 表达的 CCKBR 最多。有趣的是，当同时使用原位杂交检查这两种标志物时，观察到 CCKBR 和 CgA 的高度共表达。总之，我们发现所有 8 例 NEN 均表达 CCKBR 和神经内分泌标志物，大多数肿瘤细胞均表达这些标志物。同样的标志物也在一部分腺癌中表达，这支持胃泌素在胃癌发展中很重要的观点。
