Distinct claudin expression profile in histologic subtypes of lung cancer.
OBJECTIVE
Claudins are the main constituents of tight junctions. Little is known about their expression and localization in the normal bronchial epithelium and in lung cancer.


METHODS
One hundred four lung cancer tissue blocks were studied including 46 adenocarcinomas (ADC), 30 squamous cell carcinomas (SCC), 15 small cell lung cancers (SCLC), 8 typical and 5 atypical carcinoids. All slides contained normal bronchial mucosa as well. Immunohistochemistry using antibodies against claudins-1, -2, -3, -4, and -7 proteins, as well as semi-quantitative estimation were performed. RT-PCR analysis was also carried out in 22 immunohistochemically representative tumor samples.


RESULTS
Normal bronchial epithelial cells expressed all the examined claudin proteins. When compared, SCLCs and carcinoids showed striking differences in regard to claudins-1, -3, and -4 expressions (p<0.0001, p<0.0001, and p<0.0004, respectively), whereas ADCs and SCCs revealed significant differences in claudins-3, -4, and -7 expressions (p<0.0001, p<0.0001, and p<0.0053, respectively). However, comparison of ADCs with SCLCs revealed significant difference only in claudin-2 expression (p<0.0002). The comparison of ADCs and carcinoids resulted in significant differences regarding claudins-1, -3, and -4 expressions (p<0.0006, p<0.0001, and p<0.0001, respectively). SCCs and SCLCs varied in respect to claudin-2, -3, and -4 expressions (p<0.0009, p<0.0001, and p<0.0019, respectively), whereas SCCs and carcinoids showed different claudins-1 and -4 expressions (p<0.0076 and p<0.0045, respectively). RT-PCR analysis revealed parallel changes in the mRNA and protein expression of certain claudins.


CONCLUSIONS
The observed distinct claudin expression profile within the non-small cell lung cancer group, further, the marked differences between SCLCs and carcinoids may have differential diagnostic impact, and the overexpression of certain claudins might have therapeutic implications.
Moldvay
Judit
J
Department of Pulmonology, Semmelweis University Budapest, Budapest, Diósárok u. 1/c. H-1125, Hungary. drmoldvay@hotmail.com
Jäckel
Márta
M
Páska
Csilla
C
Soltész
Ibolya
I
Schaff
Zsuzsa
Z
Kiss
András
A
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism; D001980:Bronchi / Q000378:metabolism; D002276:Carcinoid Tumor / Q000235:genetics / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism; D062445:Claudin-1; D062465:Claudin-3; D062506:Claudin-4; D057167:Claudins; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000145:classification / Q000235:genetics / Q000473:pathology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D020545:Respiratory Mucosa / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
C568108:CLDN1 protein, human; C491875:CLDN2 protein, human; C568122:CLDN3 protein, human; C568157:CLDN4 protein, human; C473255:CLDN7 protein, human; D062445:Claudin-1; D062465:Claudin-3; D062506:Claudin-4; D057167:Claudins; D008565:Membrane Proteins; D012333:RNA, Messenger