Relationship Among Expressions Of Apoptosis-associated Proteins, Anti-durg Protein And Neuroendocrine Differentiation In NSCLC

BACKGROUND & OBJECTIVE: Apoptosis-associated protien and anti-drug protein have been proved to be the important factors correlated with anti-cancer chemotherapy efficiency in non-small cell lung carcinoma (NSCLC). The latest research showed that neuroendocrine (NE) differentiation also one of factors involved in multidrug resistance. But the relationship among them in NSCLC is not clear. This paper aims to provide an answer by studying relationship among expressions of four apoptosis -associated proteins (survivin, bcl-2, bax and PARP), two apoptosis regulating proteins (PTEN and P65), LRP and NE differentiation defined with three NE markers (NSE, SYN and CgA) in NSCLC tissues.METHODS: 113 cases of paraffin embedded NSCLC tissues were measured by stained immunohistochemically for survivin, bcl-2, bax, PARP, P65, PTEN, LRP, NSE, SYN and CgA protein using streptavidin-peroxidase Coiugated method, the results was analyzed with statistical methods.RESULTS: â‘ In 113 cases, the positive rate of survivin, bcl-2, bax, PARP protein was 88.5%, 58.4%, 54.0% and 29.2%, respectively. The positive rate of PTEN and P65 protein was 77.0% and 68.1% respectively and that of LRP was 80.5%. â‘¡Correlation analysis revealed that expression of survivin protein was related to TMN stages (P< 0.05) , expression of bcl-2 protein was related to histologic type (P<0.05) and that of bax protein, was related to NSCLC differentiation (P<0.05). Expression of bcl-2 protein significantly correlated with that of bax protein (P<0.01). Relativity was also founded between expressions of bcl-2 and survivin protein (P<0.05). â‘¢Expressions of PTEN and P65 protein were related to NSCLC differentiation (P<0.05) and there was a negative relativity between them. Expression of PTEN protein was negatively correlated with that of s;urvivin and bcl-2 protein (P<0.05). Expression of P65 protein was positively correlated with that of survivin, bcl-2 and PARP protein (P<0.01, <0.01,<0.05, respectively). ?The expression of LRP was related to NSCLC differentiation (P<0.05) while it did not correlate with other proteins (Z^O.05). ?The positive rates of the NE markers were NSE, 53.6%; SYN, 6.2%; and CgA, 26.5%. 24 samples (21.2 %) was proved to be with NE differentiation expressing at least 2 NE markers. In those NSCLC with neuroendocrine differentiation, there were remarkable lower expression of LRP and higher expressions of survivin and P65 protein.CONCLUSIONS: ?These results suggest that over-expressions of survivin, bcl-2 and PARP protein, depressed expressions of bax, PTEN protein and excessive activation of P65 protein may play an important role during NSCLC angiogenesis, apoptosis of cancer cells, cancer invasion and metastasis. (Dsurvivin protein can be regarded as a prognostic index. ?Maybe there is a negative feedback between PTEN and P65 protein. PTEN protein may suppress the expressions of survivin and bcl-2 protein while excessive activation of P65 protein clearly increase that of survivin, bcl-2 and PARP protein. ?In NSCLC, the anti-drug mechanism of LRP is not same as that of apoptosis-associated proteins. ?NSCLC with NE differentiation has obviously higher anti-apoptosis ability represented by survivin and P65 protein and lower anti-drug property characterized by LRP.