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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 nonsmallcell 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 onestep reverrrrrrrrrnsrrrrrrrrne trrrrrrrrnranscriptionpolymerase chain reaction (RTPCR) The integrated density valuerrrrrrrrns orrrrrrrrnf the PCR products were analyzed semiquantitatively 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<005) The integrated rrrrrrrrnOD valrrrrrrrrnues of TCF 4 expression was significantly higher in tumors with moderatepoorrrrrrrrrn rrrrrrrrncerrrrrrrrnll differentiation than in well differentiated tumors (5163±667 vs 4613rrrrrrrrn±12rrrrrrrrn31, P<001) 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 moderatepoor cell differentiation than in well differrrrrrrrrnerrrrrrrrnntiated tumors (P<005) There were no significant difrrrrrrrrnferences inrrrrrrrrn mRNA expression in comparison with histological type rrrrrrrrnConclusions The subcellular 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 factor4 (TCF4) plays an importa r r r r r r r nnt role in development and carcinogenesis Recently, the role of TCF4 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 TCF4 protein and r r r r r r r nmRNA in nonsmallcell 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 <005) 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 (5163 ± 667 vs 4613 r r r r r r r r n ± 12 r r r r r r r n 31, P < 01) There was no TCF4 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 <005) 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