Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang, China.
Histol Histopathol. 2010 Apr;25(4):445-52. doi: 10.14670/HH-25.445.
Japan is a high-risk region for gastric carcinoma with a comparatively early stage and favorable prognosis. To clarify the pathobiological behaviors and prognosis of Japanese gastric adenocarcinoma, we analyzed the clinicopathological characteristics of different WHO subtypes of carcinomas. The expression of ki-67, CPP32, p53, FHIT, maspin, parafibromin, GRP78, GRP94, EMMPRIN, VEGF, P-GSK3beta-ser9, fascin, cortactin, Arp2, Arp3 MUC-2, MUC-5AC and MUC-6 was examined using immunohistochemistry and tissue microarrays. The majority of cases were well-, poorly-, or moderately-differentiated subtype, whereas the minority were papillary or signet ring cell carcinoma (SRC). Patients with poorly-differentiated or SRC carcinoma were predominantly young and female. Poorly-differentiated and mucinous carcinomas were larger, with deeper invasion, more venous or lymphatic invasion, frequent lymph node involvement and peritoneal dissemination, or higher staging. The SRC group exhibited weaker expression of ki-67, CPP32, p53, parafibromin, GRP78, GRP94, P-GSK3beta-ser9, VEGF or cortactin. The moderately-differentiated subtype exhibited lower expression of FHIT and Arp3 positivity. The poorly-differentiated group showed weaker expression of CPP32, EMMPRIN, MUC-2, MUC-5AC, and MUC-6. Survival analysis indicated that the patients with poorly-differentiated or mucinous subtypes had a lower cumulative survival rate than those with papillary, well-, moderately-differentiated, or SRC carcinomas (P<0.05). The age, invasive depth, lymphatic invasion, peritoneal dissemination, and WHO classification were independent prognostic factors for carcinoma patients (P<0.05). It was suggested that poorly-differentiated and mucinous subtypes are more aggressive and of unfavorable prognosis among Japanese gastric carcinomas. Lower levels of proliferation and apoptosis, as well as alterations in tumor suppressor genes, mucin production and ER stress protein played important roles in the pathogenesis of poorly-differentiated and SRC carcinomas.
日本是胃癌的高发地区，其胃癌具有相对较早的分期和较好的预后。为了阐明日本胃腺癌的病理生物学行为和预后，我们分析了不同 WHO 组织学亚型的癌的临床病理特征。使用免疫组织化学和组织微阵列检测了 ki-67、CPP32、p53、FHIT、maspin、副肌球蛋白、GRP78、GRP94、EMMPRIN、VEGF、P-GSK3beta-ser9、 fascin、cortactin、Arp2、Arp3、MUC-2、MUC-5AC 和 MUC-6 的表达。大多数病例为高、中或低分化型，少数为乳头状或印戒细胞癌（SRC）。低分化或 SRC 癌患者主要为年轻女性。低分化和黏液腺癌较大，侵袭更深，静脉或淋巴管侵犯更频繁，淋巴结转移和腹膜播散更常见，或分期更高。SRC 组 ki-67、CPP32、p53、副肌球蛋白、GRP78、GRP94、P-GSK3beta-ser9、VEGF 或 cortactin 的表达较弱。中分化型 FHIT 和 Arp3 阳性表达较低。低分化组 CPP32、EMMPRIN、MUC-2、MUC-5AC 和 MUC-6 的表达较弱。生存分析表明，低分化或黏液型患者的累积生存率低于乳头状、高、中分化或 SRC 癌患者（P<0.05）。年龄、浸润深度、淋巴管浸润、腹膜播散和 WHO 分类是癌患者的独立预后因素（P<0.05）。提示日本胃腺癌中低分化和黏液型侵袭性更强，预后不良。增殖和凋亡水平降低以及肿瘤抑制基因、黏蛋白产生和 ER 应激蛋白的改变在低分化和 SRC 癌的发病机制中起重要作用。
