Xu Qian, Sun Li-Ping, Wang Ben-Gang, Liu Jing-Wei, Li Ping, He Cai-Yun, Yuan Yuan
Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, North Nanjing Street 155#, Heping District, Shenyang 110001, People's Republic of China.
BMC Clin Pathol. 2013 Aug 9;13(1):21. doi: 10.1186/1472-6890-13-21.
Pepsinogen C (PGC) and mucin1 (MUC1) are important physiologically functional gastric proteins; Mucin2 (MUC2) is an "ectopic" functional protein in intestinal metaplasia of gastric mucosa. We analyzed the co-expression of the above-mentioned three proteins in dynamic gastric diseases {superficial gastritis (SG)-atrophic gastritis (AG)--gastric cancer (GC)} as well as different histological types of gastric cancer in order to find molecular phenotypes of gastric cancer and precancerous disease and further explore the potential co-function of PGC, MUC1 and MUC2 in the occurrence and development of gastric cancer.
The SG-AG-GC sequence was 57-57-70 cases in this case-control study, respectively. Different histological types of GC were 28 cases of highly and moderately differentiated aden ocarcinoma (HMDA)、30 of poorly differentiated adenocarcinoma (PDA) and 12 of mucinous adenocarcinoma (MA) or signet ring cell carcinoma (SRCC). PGC, MUC1 and MUC2 expression in situ were detected in all 184 cases using immunohistochemistry.
Both PGC and MUC1 had a significantly decreased expression in GC than in SG and AG (P < 0.0001 and P < 0.01, respectively); While MUC2 had a significant increased expression in AG than in SG and GC (P < 0.0001). Seven phenotypes of PGC, MUC1 and MUC2 co-expression were found in which PGC+/MUC1+/MUC2- phenotype took 94.7%(54/57) in SG group; PGC+/MUC1+/MUC2+ and PGC-/MUC1+/MUC2+ phenotype took 43.9% (25/57) and 52.6% (30/57) in AG; the phenotypes in GC group appeared variable; extraordinarily, PGC-/MUC1-/MUC2+ phenotype took 100% (6/6) in MA or SRCC group and had a statistical significance compared with others (P < 0.05).
Phenotypes of PGC, MUC1 and MUC2 co-expression in dynamic gastric diseases are variable. In SG group it always showed PGC+/MUC1+/MUC2- phenotype and AG group showed two phenotypes (PGC+/MUC1+/MUC2+ and PGC-/MUC1+/MUC2+); the phenotypes in GC group appeared variable but the phenotype of PGC-/MUC1-/MUC2+ may be a predictive biomarker for diagnosing MA or SRCC, or distinguishing histological MA or SRCC from tubular adenocarcinoma accompanied by mucinous secretion or signet ring cell scattered distribution.
胃蛋白酶原C(PGC)和黏蛋白1(MUC1)是重要的具有生理功能的胃蛋白;黏蛋白2(MUC2)是胃黏膜肠化生中的一种“异位”功能蛋白。我们分析了上述三种蛋白在动态胃部疾病{浅表性胃炎(SG)-萎缩性胃炎(AG)-胃癌(GC)}以及不同组织学类型胃癌中的共表达情况,以寻找胃癌及癌前疾病的分子表型,并进一步探索PGC、MUC1和MUC2在胃癌发生发展中的潜在协同作用。
在这项病例对照研究中,SG-AG-GC序列分别为57-57-70例。不同组织学类型的GC包括28例高中分化腺癌(HMDA)、30例低分化腺癌(PDA)以及12例黏液腺癌(MA)或印戒细胞癌(SRCC)。采用免疫组织化学法检测了全部184例病例中PGC、MUC1和MUC2的原位表达。
与SG和AG相比,GC中PGC和MUC1的表达均显著降低(分别为P<0.0001和P<0.01);而AG中MUC2的表达显著高于SG和GC(P<0.0001)。发现了PGC、MUC1和MUC2共表达的七种表型,其中PGC+/MUC1+/MUC2-表型在SG组中占94.7%(54/57);PGC+/MUC1+/MUC2+和PGC-/MUC1+/MUC2+表型在AG组中分别占43.9%(25/57)和52.6%(30/57);GC组中的表型呈现多样化;特别的是,PGC-/MUC1-/MUC2+表型在MA或SRCC组中占100%(6/6),与其他组相比具有统计学意义(P<0.05)。
PGC、MUC1和MUC2在动态胃部疾病中的共表达表型是多样的。SG组中总是表现为PGC+/MUC1+/MUC2-表型,AG组表现为两种表型(PGC+/MUC1+/MUC2+和PGC-/MUC1+/MUC2+);GC组中的表型呈现多样化,但PGC-/MUC1-/MUC2+表型可能是诊断MA或SRCC,或区分伴有黏液分泌的管状腺癌或印戒细胞散在分布的组织学MA或SRCC的预测生物标志物。