The Study Of Expression Of Survivin, Caspase-3, And Its Signification In Gastric Adenocarcinoma Using Tissue Microarrays

Objective: To investigate the role of survivin and caspase-3 in apoptosis of gastric adenocarcinoma, as well as its relationship with the clinicopathologic features and the prognosis of gastric carcinomas.Method: The gastric cancer tissue microarrays were composed of those from 100 cases of adenocarcinoma of the stomach and 30 gastric tissues of control subject. The diameter of each specimens on tissue microarrays was 2.0 mm. Expressions of survivin, caspase-3 as well as Bcl-2 Bak P53 were investigated immunohistochemically in 100 gastric carcinoma patients without a history of chemo-radiation therapy. Tumor cell apoptosis was examined by TUNEL method. The association of the expression of these subjects was analyzed. Of the 100 cases, 47cases were follow-up from 14 months to 13 years, in which the prognosis was analyzed.Results: Two paraffin-embedded gastric cancer tissue microarrays were successfully constructed, including 114 and 116 tissue spots, respectively. Immunohistochemical analysis showed that survivin expression was positive in 78 of 100 patients (78%) with gastric carcinoma. In contrast, no expression of survivin in control tissues was detected, P <0.01. The expression of survivin was associated with histological grades, metastasis of lymph node, invading of vessel & nerve and UICC stages, P<0.05. The expression of caspase-3 was much higher in normal tissues (90%) than in carcinoma (56%),P< 0.01.Expression of caspase-3 was significantly associated with histological grades and invading of vessel & nerve, but no distinct difference was found in metastasis of lymph node and UICC stages. Patients with survivin (-) and caspase-3 (+) had the maximum apoptosis index, and patients with survivin (+) and caspase-3 (-) had the minimum apoptosis index. The expression of Bcl-2 and Bak was correlating with histological grades of carcinoma of the stomach, but no distinct difference was found in metastasis of lymphnode, invading of vessel & nerve and UICC stages. P53 expression was associated with histological grades, invading of vessel & nerve, metastasis of lymph node and UICC stages, but the difference was no significant.In the 47 cases with followed-up data, univariant analysis revealed that the survival rate was correlated with invading of vessel & nerve, UICC stages, and expression of survivin. The histological grades and the expression of caspase3 ,Bcl-2,Bak, P53 were no related to prognosis. However, Cox stepwise proportional hazards analysis showed that only UICC staging, survivin status retained significant independently in prospecting prognosis.Conclusion: To investigate the gastric carcinoma using the tissue microarrays was advantage in smaller bulk and including more information. So the tissue microarray method was a useful technique for pathology study. The expression of survivin was associated with histological grades, metastasis of lymph node, invading of vessel & nerve and UICC stages. Expression of caspase-3 was significantly associated with histological grades and invading of vessel & nerve, but no distinct difference was found in metastasis of lymph node and UICC stages. The expression of Bcl-2 and Bak was correlated with histological grades of carcinoma of the stomach, but no distinct difference was found in metastasis of lymph node, invading of vessel & nerve and UICC stages. P53 expression was associated with histological grades, invading of vessel & nerve, metastasis of lymph node and UICC stages, but the difference was no significant. The carcinoma cell with survivin (-) and caspase-3 (+) had the maximum apoptosis index, and those with survivin (+) and caspase-3 (-) had the minimum apoptosis index. The analysis with followed-up data indicates that the invading of vessel & nerve and expression of survivin may be poor prognosis factors for gastric carcinoma. Besides, UICC stage was still a useful parameter in predicting prognosis.