胃癌nm23H1 mRNA、VEGF-C mRNA表达及其与淋巴转移、生存率的相关性研究

研究胃癌组织nm23H1 mRNA、VEGF-C mRNA和VEGFR-3的表达与胃癌中的新生淋巴管的生成、肿瘤淋巴道转移和生存率关系,为临床治疗及预后提供实验依据。用胃癌与癌周组织作对照,应用原位杂交法检测78例胃癌组织nm23H1 mRNA、VEGF-C mRNA表达,并以VEGFR-3抗体为标记,经EnVisionTM免疫组织化学及Leica-Qwin计算机图像分析,用Weidner最高血管密度计数法,计数阳性淋巴管数(MLC),以及调查患者术后的生存率。胃癌nm23H1 mRNA阳性表达 69．23％(54例)、nm23H1 mRNA阳性表达与胃癌淋巴结转移、TNM分期、MLC呈负相关(P<0．01), VEGF-C mRNA阳性表达46．15％(36例),其与胃癌淋巴结转移、TNM分期、MLC呈正相关(P<0．01 或P<0．05)．与癌周组织的nm23H1 mRNA和VEGF-C mRNA表达比较,具有显著性差异(P<0．01 或P<0．05)。nm23H1 mRNA在Ⅰ、Ⅱ期胃癌中呈高表达,在Ⅲ、Ⅳ期患者中呈低或无表达。胃癌组织的MLC(8．37±2．29/mm2)显著高于癌周组织(4．51±2．64/mm2),两者比较具有显著性差异(P<0．05)。 nm23H1 mRNA与VEGFR-3表达之间存在负相关(P<0．05,r=0．8479);VEGF-C mRNA与VEG- FR-3表达之间存在正相关(P<0．05,r=0．8362)。在根治术5年内死亡的61．54％(48例)患者中 MLC(10.82±2．51/mm2)高于5年内生存的患者(6．53±2．09/mm2),两组间有显著性差异(P<0．05);在不同的肿瘤病理学分级中,胃癌未、低分化型与高、中分化型的nm23H1 mRNA阳性表达,有显著性差异(P<0．05),当nm23H1 mRNA高表达时,肿瘤淋巴转移率低,生存率高,故认为nm23H1基因具有抑制胃癌发生和淋巴道转移作用;当VEGF-C mRNA高表达时,肿瘤淋巴转移率高,生存率低。胃癌组织中的VEGFR-3表达水平与肿瘤的淋巴转移密切相关,胃癌组织MLC的显著增高,提示肿瘤组织有新淋巴管的生成。VEGF-C促进了肿瘤诱导的淋巴管新生,在胃癌的淋巴道转移中起重要作用。

STUDY ON THE CORRELATION BETWEEN THE EXPRESSIONS OF nm23H1 mRNA, VEGF-C mRNA AND LYMPHATIC METASTASES, SURVIVAL RATE WITH GASTRIC CANCER

The correlations between the expression of nm23H1 mRNA,VEGF-C mRNA, VEGFR-3 and neoangiogenesis, hyperplasia of micro-lymphatic, tumor metastases in gastric cancer were studied, the results supplied an experimental foundation for clinical treatment and prognosis. All the specimens were marked by VEGFR-3 antibody, the expressions of nm23H1 mRNA, VEGF-C mRNA were detected in 78 cases of gastric cancer in situ hybridization with EnVision and Leica-Qwin computer image analysis system. The Weidner's highest vessel density counting method was used to analyse micro-lymphatics count (MLC) of the specimens, and the patients' viability after operation was investigated. The positive expression of nm23H1 mRNA in gastric cancer was 69.23% (54 cases). There was negative correlation between the positive expression of nm23H1 mRNA and lymph node metastasizing, TNM staging, MLC (P < 0.01 or P < 0.05). The expression of VEGF-C mRNA was 46.15% (36 cases). It was positive related to the lymph node metastasis, TNM stages, MLC in gastric cancer (P < 0.01 or P < 0.05), and was significantly different compared with adjacent nontumorous tissue (P < 0.01 or 0.05). The expression of nm23H1 in stage I and II gastric cancer was high, while in stage III and IV the expression was lower or even none. The MLC (8.37 +/- 2.29/mm2) in gastric cancer was higher than that in adjacent nontumorous tissue (4.82 +/- 3.48/mm2), which has statistical significance (P < 0.05). There was negative correlation between the expression of nm23H1 mRNA and VEGFR-3 (p < 0.05, r = 0.8479), but positive correlation between VEGF-C mRNA and VEGFR-3 (P < 0.05, r = 0.8362). The MLC (10.82 +/- 2.51/mm2) in those who died in five years (48 cases) was higher than that (6.53 +/- 2.09/mm2) in those who were still alive, the difference has statistical significance (P < 0.05). In different tumor pathology grading, different differentiation, the nm23H1 positive expression is significantly different (P < 0.05). Higher the nm23H1 expressed, lower the tumor lymph metastasized, but the viability rate was higher, so the nm23H1 gene was thought to have the effect of suppressing gastric cancer occurring and lymph metastasizing. Higher the VEGF-C mRNA expressed, higher the tumor lymph metastasized, but the viability rate was lower. There is close correlation between the VEGFR-3 expression and gastric cancer lymph metastasizing. The higher MLC level indicated neoangiogenesis in gastric cancer. VEGF-C promote neoangiogenesis induced by tumor and play an important role in lymph metastasizing.