Expressions Of Anti-apoptosis Gene Survivin In Esophageal Carcinoma And Its Relationship With P33～(ING1), Mcm5 And PCNA

Objective: It is necessary for the balance of the proliferation and apoptosis to stabilize cell amounts and eliminate aberrant cells in case of carcinoigenesis. The proliferation, differentiation and apoptosis of normal cells are strictly controlled by a lot of genes and balance disorders among these factors are closely correlated with the carcinogenesis and development of cancers. As many cancers, the carcinogenesis and development of esophageal carcinoma not only involves activation of proto-oncogene and inhibition of antioncogene, but also involves cell proliferation and apoptosis factors. In this study, reverse transcriptase-polymerase chain reaction(RT-PCR) and immunohistochemical technique were used to investigate survivin, p33ING1, Mcm5 and PCNA expressions in esophageal carcinoma and study the significance of survivin expressions and its relationship with apoptosisCpSBING1) and proliferation(Mcm5, PCNA) factors.Methods: The expressions of survivin mRNA in 52 esophageal surgical specimens were examined by RT-PCR, and the expressions of survivin and p33ING1 in 157 esophageal surgical specimens and the expressions of Mcm5 and PCNA in 187 esophageal biopsy specimens were examined by immunohistochemical technique(S-P). Results:1. Survivin protein showed 82.2% positive expressions in esophageal carcinoma, which were significantly higher than those in normal epithelium(22.3%). Survivin positive staining in carcinoma was located in cytoplasm, or both in cytoplasm and nucleus. Survivin expressions had no correlation with the grading, invasive depth and lymph metastasis of carcinoma. Survivin expressions in cytoplasm and nucleus also had no correlation with the grading, but had correlation with the invasive depth and lymph metastasis of carcinoma. The positive rates of survivin nuclear expressions in deep invasive group(49.0%) and metastatic group(61.8%) were significantly higher than those in superficial invasive group(21.8%) and non-metastatic group(27.5%).2. Survivin/ actin ratio(0.6169 0.2294) and survivin mRNA positive rate(78.8%) in esophageal carcinoma were both significantly higher than those in normal epithelium(0.2338 0.1810, 21.2%). Survivin mRNA expressions had no correlation with the grading, invasive depth and lymph metastasis of carcinoma. The result of RT-PCR was consistent with that of immunohistochemistry.3. pSS1 protein showed 50.8% positive expressions in esophageal carcinoma, which were significantly lower than those in normal epithelium(96.7%). pSS expressions had no correlation with the invasive depth and lymph metastasis, but had correlation with the grading of carcinoma. The positive rate of pSS protein expressions in grade I group(70.7%) was significantly higher than those in grade II group(51.1%) and grade III group(39.3%). There was negative correlation between survivin and pSS protein expressions.4. Survivin staining was heterogeneous in esophageal biopsy specimens. Survivin positive staining was observed either in cytoplasm or nucleus, or both in cytoplasm and nucleus. Both Mcm5 and PCNA staining were located in nucleus. Survivin,4cm5 and PCNA expressions were all gradually increased in a series of lesions from normal epithelium, dysplasia, to carcinoma and they had positive correlation with the lesion degree. Survivin, Mcm5 and PCNA expressions in normal epithelium were significantly lower than those in dysplasia, carcinoma in situ and invasive carcinoma. Survivin expressions were positively correlated with Mcm5 and PCNA. In invasive carcinoma, Mcm5 and PCNA median labeling indexes in survivin positive group were significantly higher than those in survivin negative group. Conclusion:1. Survivin showed high expressions in esophageal carcinoma, but no or weak expressions in normal epithelium. It was indicated that survivin gene activation and expression was correlated with the carcinogeniesis and development of esophageal carcinoma. Apoptosis inhibition by survivin may be one of the key mechanisms in the carcinogenesis of esophageal carcinoma.2. Survivin protein expres...