Claudin-1 and claudin-5 expression patterns differentiate lung squamous cell carcinomas from adenocarcinomas.
We investigated the expression of tight junction proteins in human lung squamous cell carcinomas and adenocarcinomas by immunohistochemistry and quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR). We found a statistically significant correlation between diagnosis and positivity of tumors with either claudin (CLDN)-1 or CLDN-5. Squamous cell carcinomas and basal cells of bronchial epithelium were positive for CLDN-1 and negative for CLDN-5, whereas adenocarcinomas, normal cylindrical cells and pneumocytes were positive for CLDN-5 and negative for CLDN-1, suggesting different pathways in tumor development and progression. CLDN-4 and ZO-1 staining were detected in both types of tumors, whereas cingulin (CGN) was not detected in squamous cell carcinomas. Quantitative RT-PCR was used to evaluate changes in transcript levels for a large panel of tight junction proteins. In squamous cell carcinomas, we observed statistically significant decreases in the mRNA levels of JAM-1, occludin, CLDN-3, CLDN-4, CLDN-7, CGN, ZO-2 and ZO-3, and an increase in CLDN-1 mRNA. In adenocarcinomas, when transcript levels were compared with bronchial cells, we observed statistically significant decreases in the mRNA levels of CLDN-1, CLDN-3, CLDN-4, CLDN-7, ZO-2 and ZO-3. These results indicate that characterization of tight junction protein expression in human lung tumors can be an additional diagnostic tool and provide new insights on their histogenesis.
Paschoud
Serge
S
Department of Molecular Biology, Faculty of Sciences, University of Geneva, Geneva, Switzerland.
Bongiovanni
Massimo
M
Pache
Jean-Claude
JC
Citi
Sandra
S
D000230:Adenocarcinoma / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D062445:Claudin-1; D062506:Claudin-4; D062507:Claudin-5; D003937:Diagnosis, Differential; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000032:analysis* / Q000235:genetics; D008840:Microfilament Proteins / Q000032:analysis; D008875:Middle Aged; D009367:Neoplasm Staging; D010750:Phosphoproteins / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019108:Tight Junctions / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D062826:Zonula Occludens-1 Protein
D014408:Biomarkers, Tumor; C061407:CGN protein, human; C568108:CLDN1 protein, human; C568157:CLDN4 protein, human; C107466:CLDN5 protein, human; D062445:Claudin-1; D062506:Claudin-4; D062507:Claudin-5; D008565:Membrane Proteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein