Lou Lei, Wang Yuan, Cui Jinfeng, Yan Xia, Xue Liying, Li Yuehong
Department of Pathology, The Second Hospital, Hebei Medical University, Shijiazhuang, China.
Tumour Biol. 2014 May;35(5):5029-36. doi: 10.1007/s13277-014-1664-z. Epub 2014 Feb 2.
Gastric cardia adenocarcinoma (GCA) is distinct from adenocarcinoma of the distal stomach because of its different etiological factors, tumor characteristics, and biological behavior. However, its pathogenesis is not fully understood. The purpose of this study is to characterize the role of Pim-3, c-Myc, and p-p27 in the tumorigenesis and progression of different sites of gastric adenocarcinoma by determining its pathogenetic significance. The expression of Pim-3, c-Myc, and p-p27 proteins was evaluated by immunohistochemistry in 140 resection specimens of gastric adenocarcinomas (78 GCAs , 62 DGAs and 20 normal gastric tissues). The level of expression of Pim-3, c-Myc, and p-p27 and the co-expression of all three markers (Pim-3+/c-Myc+/p-p27+) in GCA were significantly lower than that in DGA tumors (P < 0.05). Detailed analysis of the immunoreactivity patterns showed that in DGA, Pim-3 immunoreactivity was associated significantly with poor tumor differentiation, advanced tumor stage, and presence of lymph node metastasis. In addition, c-Myc overexpression correlated with tumor stage and lymph node metastasis, and positive p-p27 expression correlated with poor differentiation and tumor stage. The phenotype of Pim-3(+)/c-Myc(+)/p-p27(+) co-expression was closely correlated with tumor stage and lymph node metastasis (P < 0.05). In contrast, GCA only demonstrated a close correlation of Pim-3 overexpression with poor tumor differentiation and tumor stage (P < 0.05). Our results demonstrate the presence of different expression patterns of Pim-3, c-Myc, p-p27, and Pim-3(+)/c-Myc(+)/p-p27(+) and their clinicopathologic significance in GCA and DGA tumors. Our results add support to the notion that distinct molecular mechanisms may be involved in the development and progression of adenocarcinomas from the gastric cardia and distal portion of stomach.
贲门腺癌（GCA）因其病因、肿瘤特征及生物学行为不同，与远端胃癌腺癌有所区别。然而，其发病机制尚未完全明确。本研究旨在通过确定Pim-3、c-Myc和p-p27在胃腺癌不同部位肿瘤发生及进展中的致病意义，来明确它们的作用。采用免疫组织化学方法评估了140例胃腺癌切除标本（78例GCA、62例远端胃癌腺癌[DGA]和20例正常胃组织）中Pim-3、c-Myc和p-p27蛋白的表达。GCA中Pim-3、c-Myc和p-p27的表达水平以及这三种标志物的共表达（Pim-3+/c-Myc+/p-p27+）均显著低于DGA肿瘤（P < 0.05）。对免疫反应模式的详细分析表明，在DGA中，Pim-3免疫反应性与肿瘤低分化、肿瘤晚期及淋巴结转移显著相关。此外，c-Myc过表达与肿瘤分期和淋巴结转移相关，p-p27阳性表达与低分化和肿瘤分期相关。Pim-3(+)/c-Myc(+)/p-p27(+)共表达的表型与肿瘤分期和淋巴结转移密切相关（P < 0.05）。相比之下，GCA仅显示Pim-3过表达与肿瘤低分化和肿瘤分期密切相关（P < 0.05）。我们的结果表明，Pim-3、c-Myc、p-p27和Pim-3(+)/c-Myc(+)/p-p27(+)在GCA和DGA肿瘤中存在不同的表达模式及其临床病理意义。我们的结果支持了贲门和胃远端腺癌的发生和进展可能涉及不同分子机制这一观点。
