应用组织芯片技术研究胃癌组织MVD、MLD和PTEN的表达及其意义

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目的探讨PTEN在胃癌、癌旁组织中表达及微血管密度(microvessel density,MVD)、微淋巴管密度(microlymphatic density,MLD),分析其表达水平与临床病理特征和生存期的关系。方法用组织芯片和免疫组化的方法检测189例胃癌组织、54例癌旁组织、32例正常胃黏膜中PTEN的表达及微血管密度、微淋巴管密度。结果胃癌、癌旁和正常胃黏膜组织PTEN阳性表达率分别是50.8%(96/189)、85.2%(46/54)和96.9%(31/32),胃癌组织PTEN阳性表达率显著低于癌旁和正常胃黏膜组织(χ2=19.330,P=0.000;χ2=22.830,P=0.000)。PTEN阳性表达与有无淋巴结转移、分化程度和Lauren分型有关(P<0.05)。胃癌组织MVD和MLD分别显著高于癌旁组织和正常胃黏膜组织[MVD:(28.84±14.17)vs(17.02±8.54)、(16.69±7.21);MLD:(8.55±4.98)vs(4.05±2.48)、(3.99±1.56);P<0.01]。微血管密度与分化程度、Lauren分型及浸润深度密切相关(P<0.01);微淋巴管密度则与分化程度、Lauren分型及淋巴结转移密切相关(P<0.05);微血管密度、微淋巴管密度在PTEN阴性表达组显著高于阳性表达组[MVD:(31.37±15.14)vs(26.86±13.29),P=0.031;MLD:(9.37±4.23)vs(7.61±5.29),P=0.012]。PTEN的表达和MVD(r=-0.168,P=0.021)、MLD(r=-0.283,P=0.000)呈负相关关系。生存分析显示:低MVD较高MVD具有生存优势(χ2=4.224,P=0.040),MLD与生存无相关性(χ2=1.044,P=0.307),PTEN阳性表达具有显著的生存优势(P<0.05),是独立于胃癌分期、分级和分型的生存期预测因子。结论PTEN低表达参与胃癌的发生、发展和浸润转移,是胃癌发生的晚期事件。失表达的PTEN可增加胃癌组织MVD、MLD。PTEN的表达可以作为胃癌预后的独立指标。 Objective To investigate the expression of PTEN in gastric cancer and paracancerous tissues and its relationship with the microvessel density (MVD) and microlymphatic density (MLD). The relationship between the expression of PTEN and clinicopathological features and survival was analyzed. Methods Tissue microarray and immunohistochemistry were used to detect the expression of PTEN and the microvascular density and lymphatic vessel density in 189 cases of gastric cancer tissues, 54 cases of paracancerous tissues and 32 cases of normal gastric mucosa. Results The positive rates of PTEN in gastric cancer, paracancer and normal gastric mucosa were 50.8% (96/189), 85.2% (46/54) and 96.9% (31/32), respectively. The positive rate of PTEN in gastric cancer was significantly lower than that in cancer Paraxial and normal gastric mucosa (χ2 = 19.330, P = 0.000; χ2 = 22.830, P = 0.000). The positive expression of PTEN was correlated with lymph node metastasis, differentiation and Lauren classification (P <0.05). MVD and MLD in gastric cancer tissue were significantly higher than those in paracancerous tissues and normal gastric mucosa [MVD: (28.84 ± 14.17 vs 17.02 ± 8.54, (16.69 ± 7.21, MLD: (8.55 ± 4.98) vs (4.05 ± 2.48 ), (3.99 ± 1.56); P <0.01]. The microvessel density was closely related to the degree of differentiation, Lauren’s classification and the depth of invasion (P <0.01). The micro-lymphatic vessel density was closely related to the degree of differentiation, Lauren’s classification and lymph node metastasis (P <0.05) (P <0.01); MLD: (9.37 ± 4.23) vs (7.61 ± 5.29), P = 0.012] in PTEN-negative group was significantly higher than that in positive group [MVD: (31.37 ± 15.14) vs (26.86 ± 13.29), P = 0.031; The expression of PTEN was negatively correlated with MVD (r = -0.168, P = 0.021) and MLD (r = -0.283, P = 0.000). Survival analysis showed that MVD with low MVD had survival advantage (χ2 = 4.224, P = 0.040), MLD had no correlation with survival (χ2 = 1.044, P = 0.307) ), Is independent of gastric cancer staging, grading and classification of survival predictors. Conclusion The low expression of PTEN is involved in the occurrence, development and invasion and metastasis of gastric cancer, which is a late event of gastric cancer. The loss of expression of PTEN can increase gastric cancer MVD, MLD. PTEN expression can be used as an independent indicator of gastric cancer prognosis.
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