Expression of T cell factor-4 in non-small-cell lung cancer

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Background T cell factor 4 (TCF 4) plays an importarrrrrrrrnnt role in development and carcinogenesis Recently, the role of TCF 4 has berrrrrrrrnenrrrrrrrrn described in colon cancer andrrrrrrrrn other cancers However, whether TCF 4 plays a similar role in lung cancer isrrrrrrrrn rrrrrrrrnunknown To answer this question, we studied the expression of TCF 4 protein and rrrrrrrrnmRNA in nonsmallcell lung cancer (NSCLC) and the relation of TCF 4 expressrrrrrrrrnirrrrrrrrnon pattern to histological type and cell differentiation rrrrrrrrnMethods Tissue samples frrrrrrrrnrrrrrrrrrnom sixty cases of pathologically diagnosed NSCLC and eighrrrrrrrrnt rrrrrrrrnnormal tissue samples were obtained between September 2001 and March 2003 Immurrrrrrrrnnrrrrrrrrnohistochemistry was used to investigate the distribution of TCF 4 protein Thrrrrrrrrnerrrrrrrrn srrrrrrrrntaining patterns of the tumors were divided into 4 categories: nuclear staining rrrrrrrrnalone or nuclear staining greater than cytoplasmic staining; cytoplasmic staininrrrrrrrrng or cytoplasmic staining greater than nuclear staining; equal nuclear and cytoprrrrrrrrnlasmic staining; no nuclear staining or cytoplasmic staining The integrated oprrrrrrrrntrrrrrrrrnical density (OD) values of all sections were analyzed by UIC MetaMorph image anrrrrrrrrnalysis software The expression of TCF 4 mRNA was detected by onestep reverrrrrrrrrnsrrrrrrrrne trrrrrrrrnranscriptionpolymerase chain reaction (RTPCR) The integrated density valuerrrrrrrrns orrrrrrrrnf the PCR products were analyzed semiquantitatively rrrrrrrrnResults Immunohistochemistrrrrrrrrnry showed that there was no expression of TCF 4 in normal tissue However, TCrrrrrrrrnFrrrrrrrrn 4rrrrrrrrn was expressed in 86.7% (52/60) of NSCLC samples, mainly in the nuclei of tumor rrrrrrrrncells Furrrrrrrrnrrrrrrrrrnthermore, there was a significant difference in TCF 4 localization patterns berrrrrrrrntrrrrrrrrnwrrrrrrrrneen squamous cell carcinomas and adenocarcinomas (P<005) The integrated rrrrrrrrnOD valrrrrrrrrnues of TCF 4 expression was significantly higher in tumors with moderatepoorrrrrrrrrn rrrrrrrrncerrrrrrrrnll differentiation than in well differentiated tumors (5163±667 vs 4613rrrrrrrrn±12rrrrrrrrn31, P<001) There was no TCF 4 mRNA expression in normal tissue Howrrrrrrrrnerrrrrrrrnver, 63.9% (23/36) rrrrrrrrnof carcinoma samples expressed TCF 4 mRNA TCF 4 mRNA expression was signifrrrrrrrrnicrrrrrrrrnantrrrrrrrrnly higher in tumors with moderatepoor cell differentiation than in well differrrrrrrrrnerrrrrrrrnntiated tumors (P<005) There were no significant difrrrrrrrrnferences inrrrrrrrrn mRNA expression in comparison with histological type rrrrrrrrnConclusions The subcellular rrrrrrrrndistribution of TCF 4 may correlate with NSCLC histological type High expresrrrrrrrrnsrrrrrrrrniorrrrrrrrnn of TCF 4 mRNA and protein may be associated with the degree of cell differenrrrrrrrrntrrrrrrrrniation in NSCLC Background T cell factor4 (TCF4) plays an importa r r r r r r r nnt role in development and carcinogenesis  Recently, the role of TCF4 has be r r r r r r r r nen r r r r r r r r n Description in colon cancer and r r r r r r r r n other cancers However, whether TCF-4 plays a similar role in lung cancer is r r r r r r r r n r r r r r r r r nunknown To answer this question, we studied the expression of TCF4 protein and r r r r r r r nmRNA in nonsmallcell lung cancer (NSCLC) and the relation of TCF-4 express r r r r r r r ni r r r r r r r non pattern to histological type and cell differentiation r r r r r r r nMethods Tissue samples f r r r r r r r r nr r r r r r r r r nom sixty cases of pathologically diagnosed NSCLC and eigh r r r r r r r nt r r r r r r r r nnormal tissue samples were obtained between September 2001 and March 2003 Immu r r r r r r r r nn r r r r r r r r nohistochemistry was used to investigate the distribution of TC F  4 protein  Th r r r r r r r r ne r r r r r r r r ns r r r r r r r r ntaining patterns of the tumors were divided into 4 categories: nuclear staining r r r r r r r nalone or nuclear staining greater than cytoplasmic staining; cytoplasmic stainin r r r r r r r ng or cytoplasmic staining greater than nuclear staining; equal nuclear and cytop r r r r r r r nlasmic staining; no nuclear staining or cytoplasmic staining The integrated op r r r r r r r nt r r r r r r r n values ​​of all sections were analyzed by UIC MetaMorph image an r r r r r r r nalysis software The expression of TCF-4 mRNA was detected by one -step rever r r r r r r r r ns r r r r r r r r ne t r r r r r r r r n nranscription Olympus chain reaction (RT-PCR)  The integrated density value r r r r r r r r r r r r r r r r r r nf the PCR products were analyzed semi -quantitatively r r r r r r r nResults Immunohistochemist r r r r r r r r nry showed that there was no ex pression of TCF-4 in normal tissue. However, TC r r r r r r r nF r r r r r r r r n-4 r r r r r r r r n was expressed in 86.7% (52/60) of NSCLC samples, mainly in the nuclei of tumor r r r r r r r r ncells Fu r r r r r r r r nr r r r r r r r nthermore, there was a significant difference in TCF-4 localization patterns be r r r r r r r r nt r r r r r r r r nw r r r r r r r r neen squamous cell carcinomas and adenocarcinomas (P <005)  The integrated r r r r r r r r nOD val r r r r r r r r nues of TCF-4 expression was significantly higher in tumors with moderate-poor r r r r r r r r n r r r r r r r nce r r r r r r r nll differentiation than in well differentiated tumors (5163 ± 667 vs 4613 r r r r r r r r n ± 12 r r r r r r r n  31, P < 01)  There was no TCF4 mRNA expression in normal tissue  How r r r r r r r r ne r r r r r r r nver, 63.9% (23/36) r r TCF-4 mRNA expression was signif r r r r r r r r r n r r r r r r r nant r r r r r r r nly higher in tumors with moderate-poor cell differentiation than in differ differ r r r r r r r r r r r r r r r n nntiated tumors (P <005)  There were no significant dif r r r r r r r r nferences in r r r r r r r n mRNA expression in comparison with histological type  r r r r r r r r nConclusions The sub -cellular r r r r r r r ndistribution of TCF-4 may correlate with NSCLC histological type  High expres r r r r r r r r ns r r r r r r r n r r r r r r r r n of TCF-4 mRNA and protein may be associated with the degree of cell differen r r r r r r r nt r r r r r r r niation in NSCLC 
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