| Objective: To investigate the expression of Smac, Survivin, PCNA in small cell lung carcinoma (SCLC) and poorly differentiated squamous-cell carcinoma (PDSCC) and to explore their correlation with clinicopathologic characteristics and prognosis, hoping to provide a theoretic basis for clinical diagnosis, treatment and predicting prognosis.Methods: The expression of Smac, Survivin and PCNA were detected by S-P immunohistochemical (IHC) stain in SCLC and PDSCC. The contents of Smac, Survivin in SCLC and PDSCC were quantitatively evaluated by flow cytometry (FCM). The expression of PCNA mRNA was examined with reverse transcription-polymerase chain reaction (RT-PCR) in normal lung tissue, SCLC and PDSCC. All data were analysized by SPSS 11.5 for Windows.Results: 1 The analysis of biological features: In 32 SCLC and 40 PDSCC, the positive rate of lymph node metastasis and tumor embolus were 75.00%, 40.00% and 93.75%, 65.0% respectively, with significant difference in each group (P<0.05). SCLC owned an easier age of onset and a more advanced stage than PDSCC (P<0.05). However, there were no differences in sex and tumor maximal diameter (P>0.05).In 72 lung cancer, Kaplan-Meier survival analysis suggested that three-year survival rates of SCLC and PDSCC each were 31.25% and 65.00%, differences were significant (P<0.05).Three-year survival rates of negtive lymph node metastasis and positive metastasis were 87.50% and 20.00%, three-year survival rates of negtive tumor embolus and positive embolus were 87.50% and 39.29%, with significant differences respectively (P<0.05). Clinical stage also had effect on life span, three-year survive rates of the patients with advanced stage were low (P<0.05). Sex, age, tumor size and bronchus stump were finded not to be the prognostic factors (P>0.05). Analyzing aforesaid prognostic agents by Cox regression, we found that histotype and lymph node metastasis were independent prognostic indicators (P<0.05).2 The immunohistochemical staining results: In SCLC and PDSCC, the high expression rates of Smac were 43.75%, 67.50%, the positive expression rates of survivin were 78.13%, 50.00%, with significant differences respectively (P<0.05). However, there is no obvious difference in PCNA expression between SCLC and PDSCC (P<0.05).In SCLC, PCNA expression was not correlated with age, sex, tumor size and tumor embolus (P>0.05), but with lymph node metastasis and the expression in positive metastasis was higher than that in the negative (P<0.05). There was significant positive correlation between PCNA expression and clinical stage (r=0.381,P<0.05). The expression of Smac, Survivin were not related to all these clinicopathologic characteristics (P>0.05).In PDSCC, PCNA, Smac and Survivin expression were not correlated with sex, age and tumor size (P>0.05), but with lymph node metastasis and tumor embolus, the expression of PCNA and Survivin in positive group were higher than that in homologous negative group (P<0.05), and Smac was converse (P<0.05). There was positive correlation between PCNA expression and clinical stage (r=0.378 , P<0.05); Smac expression was related to clinical stage too, in advanced stage, the exression was low (P<0.05); However, there was no relation between Survivin expression and clinical stage (P>0.05).Spearman correlation analysis indicated that, there were no relations among the expression of Smac, Survivin and PCNA in SCLC (P>0.05). In PDSCC, there were significant negative correlation between the expression of Survivin, PCNA and Smac (r=-0.378, P<0.05,r=-0.468, P<0.05); The expression of Survivin and PCNA was coincident (r=0.518, P<0.05).3 The expression of proteins and prognosis: In 72 lung cancer, K-M survival analysis suggested that three-year survival rates of patients with high expression of Smac (70.73%) was higher than those with low expression (22.58%) (P<0.05); three-year survival rates in positive group of Survivin (31.11%) was lower than that in negative group (81.48%) (P<0.05); PCNA expression was correlated with prognosis too, three-year survival rates of patients with high expression of PCNA was low (P<0.05). But Cox regression analysis demonstrated that only the expression of Smac among the three proteins was independent prognostic indicators (P<0.05).In 32 SCLC, by univariate analysis, following variables were observed to be significantly associated with life span: lymph node metastasis (P<0.05), PCNA expression (P<0.05), Smac expression (P<0.05) and Survivin expression (P<0.05). On multivariate analysis, following variables had significant effect on prognosis: lymph node metastasis (P<0.05), Smac expression (P<0.05).In 40 PDSCC, by univariate analysis, following factors were observed to be significantly associated with life span: lymph node metastasis (P<0.05), tumor embolus (P<0.05), clinical stage (P<0.05), PCNA expression (P<0.05), Smac expression (P<0.05) and Survivin expression (P<0.05). On multivariate analysis, following variables had significant effect on prognosis: lymph node metastasis (P<0.05), Smac expression (P<0.05) and PCNA expression (P<0.05).4 The protein relative level detected by FCM: In SCLC and PDSCC, the protein relative content of Smac were (523.58±63.96),(554.95±47.54), the protein relative level of Survivin were (622.52±47.33),(591.47±63.46), differences were significant (P<0.05). The content of Smac was lower in SCLC than that in PDSCC, while survivin level was converse. These results were consistent with immunohistochemical results.In SCLC, the level of Smac, Survivin were not related to age, sex, tumor size, lymph node metastasis, tumor embolus and clinical stage (P>0.05). These results were consistent with immunohistochemical results.In PDSCC, Smac content were (535.88±44.98), (567.66±45.73) and Survivin content were (620.60±48.24), (572.05±65.78) in positive lymph node metastasis and the negative group respectively, with significant differences (P<0.05). Smac content were (542.57±42.90), (577.94±48.64) and Survivin content were (607.35±56.80), (561.98±66.62) in positive tumor embolus and the negative group respectively, with significant differences (P<0.05). The content of Smac, Survivin were not related to age, sex and tumor size (P>0.05). Aforesaid results were consistent with IHC results. But, in clinical stage, the results of IHC and FCM was disparity (P>0.05).4 The reverse transcription-polymerase chain reaction results: PCNA mRNA had low level expression in normal lung tissue,and it,s expression increased significantly both in SCLC and PDSCC. PCNA mRNA expression was slightly higher in SCLC than that in PDSCC,but without significant difference; The result was consistent with IHC results.Conclusion: 1 Lymph node metastasis may be used as an independent prognostic indicator with tumor embolus and clinical stage as reference indexs in SCLC and PDSCC. Comparing with PDSCC, SCLC prognosis was worse, with easier age of onset, higher rate of lymph node metastasis and hematogenous metastasis, more advanced clinical stage. 2 The expression of Smac was significantly lower in SCLC than that in PDSCC, low expression predicting low survival rates, accordingly, which further showed that the prognosis of SCLC was worse than that of PDSCC. Smac may be used as an independent prognostic indicator in SCLC. In PDSCC, Smac expression is related to metastasis and clinical stage and may be used as an independent prognostic factor.3 The expression of Survivin was significantly higher in SCLC than that in PDSCC, high exression indicating low survival rate, with reference index instead of independent prognostic predictor. In PDSCC, Survivin expression was correlated with lymph node metastasis, high exression predicting metastasis, so may be used to judge prognosis with lymph node.4 The expression of PCNA had no difference in SCLC and PDSCC, which indicated that the reproductive activity between them was identical. In the two types, PCNA expression was related to lymph node metastasis and clinical stage. High proliferation tumor is easy to metastasis, with more advanced clinical stage. PCNA may be used as an independent prognostic indicator in PDSCC. In SCLC, however, it only was a reference index in spite of high expression of PCNA predicting low survival rate.5 In PDSCC, the expression of PCNA was consistent with Survivin expression, while negatively correlated with Smac expression, all showed that positive expression of Survivin and low expression of Smac may promote the proliferation of transformants, which enlarged the gap between proliferation and apoptosis and caused tumor cell to gain growth vigor. The negative correlation between Smac and Survivin showed that Smac expression may regulate the expression of Survivin negatively. |
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