PTEN编码产物在胃癌发生发展不同阶段中的表达及意义

目的观察抑癌基因PTEN编码蛋白在癌旁胃黏膜、肠上皮化生、异型增生及胃癌组织中的表达,探讨PTEN表达在胃癌发生发展过程中的作用.方法采用SABC免疫组化方法检测了184例胃癌及癌旁胃黏膜、肠上皮化生和异型增生中的PTEN蛋白表达,比较其与胃癌的临床病理分期、淋巴结转移、Lauren分型及组织学分型的关系.并检测了其中60例胃癌中血管内皮生长因子(VEGF)的蛋白表达,比较VEGF与PTEN蛋白表达的关系.结果 PTEN蛋白在癌旁胃黏膜、肠化生、异型增生和胃癌中的阳性表达率分别为100.0%(102/102)、98.5%(65/66)、66.7%(4/6)和47.8%(88/184),后两者的阳性率均显著低于前两者(P<0.01);进展期胃癌PTEN表达显著低于早期胃癌( 42.9%∶67.6%,P<0.01);PTEN蛋白表达降低与胃癌淋巴结转移呈显著正相关(40.3%∶ 63.3%, P< 0.01);弥漫型胃癌PTEN表达显著低于肠型胃癌(41.5%∶57.8%,P<0.05);印戒细胞癌中PTEN表达最低(25.0%,7/28),显著低于高中分化管状腺癌(P< 0.01).PTEN蛋白与VEGF蛋白表达呈负相关趋势,但差异无显著性(P>0.05).结论 PTEN基因编码蛋白在胃癌发生发展不同阶段表达呈进行性下调或缺失,可能系通过降低细胞黏附、促进血管形成和提高细胞运动性等途径参与胃癌的发生和演进过程.PTEN蛋白表达水平可作为判定胃癌病理生物学行为的客观指标.

Expression of PTEN-encoding product in different stages of carcinogenesis and progression of gastric carcinoma

OBJECTIVE: To illustrate the significance of expression of phosphatase and tensin homologue derived from chromosome ten (PTEN) encoding product in normal mucosa, intestinal metaplasia (IM), dysplasia and carcinoma of the stomach, and to evaluate its clinical implication in tumorigenesis and progression of gastric carcinoma. METHODS: Formalin-fixed and paraffin-embedded tissues from 184 cases of gastric carcinoma, its adjacent normal mucosa, IM and dysplasia were evaluated for the expression of PTEN by SABC immunohistochemistry. PTEN expression was assessed as to tumor stage, lymph node metastasis, Lauren's classification and WHO histological classification of gastric carcinoma. Expression of VEGF protein was also studied in 60 cases of gastric carcinoma, with its correlation with PTEN concerned. RESULTS: The positive rates of PTEN protein were 100% (102/102), 98.5% (65/66), 66.7% (4/6) and 47.8% (88/184) in normal mucosa, IM, dysplasia and carcinoma of stomach, respectively. The positive rates in the last two groups were lower than the first two (P < 0.01). PTEN was less expressed in advanced gastric carcinoma than in early ones (42.9% vs 67.6%, P < 0.01). The positive rate of PTEN protein was lower in gastric carcinoma with lymph node metastasis than without (40.3% vs 63.3%, P < 0.01). PTEN was less expressed in diffuse-type gastric carcinoma than in intestinal-type (41.5% vs 57.8%, P < 0.05). Signet ring cell carcinoma expressed PTEN stood the lowest (25.0%, 7/28), which was less than well and moderately differentiated ones (61.8%, 21/34) (P < 0.01). Expression of PTEN was inversely correlated with expression of VEGF though without any significance (P > 0.05). CONCLUSION: Loss or reduced expression of PTEN protein is common in carcinogenesis and progression of gastric cancer. Altered expression of PTEN may contribute to carcinogenesis and progression of gastric cancer by increasing angiogenesis, cellular adhesion and mobility and so on. PTEN may be an objective marker for pathologically biological behavior of gastric carcinoma.