RT Journal Article
SR Electronic
T1 Diagnostic and prognostic impact of desmocollins in human lung cancer
JF Journal of Clinical Pathology
JO J Clin Pathol
FD BMJ Publishing Group Ltd and Association of Clinical Pathologists
SP 1100
OP 1106
DO 10.1136/jclinpath-2011-200630
VO 65
IS 12
A1 Tiantian Cui
A1 Yuan Chen
A1 Linlin Yang
A1 Masoud Mireskandari
A1 Thomas Knösel
A1 Qing Zhang
A1 Lukas Herbert Kohler
A1 Almut Kunze
A1 Norbert Presselt
A1 Iver Petersen
YR 2012
UL http://jcp.bmj.com/content/65/12/1100.abstract
AB Objective Desmosomes are intercellular junctions that confer strong cell–cell adhesion. Two main members of desmosomal cadherins, desmogleins (DSGs) and desmocollins (DSCs), are involved in carcinogenesis. However, their role in human lung cancer remained elusive. The aims of this study were to analyse the expression of DSCs and to evaluate their clinical application in lung cancer. Methods The expression of DSC1-3 mRNAs was analysed by RT-PCR. The methylation status of DSCs was analysed by demethylation tests and bisulphite sequencing. Protein expression of DSCs in primary lung cancer was evaluated by immunohistochemistry on tissue microarrays. Results DSC1-3 mRNAs were downregulated in lung cancer cells, and the expression was restored in four out of seven cell lines, respectively, after 5-aza-2′-deoxycytidine treatment. A heterogeneous methylation pattern was detected by bisulphite sequencing in exon 1 of DSC2 and DSC3. In 199 patients with primary lung cancer, we found that lower protein expression of DSC1 was significantly linked to worse tumour differentiation (p=0.017), DSC3 proteins were more expressed in squamous cell carcinoma (SCC) compared with adenocarcinoma (ADC) (p<0.001), and reduced expression of DSC1 and DSC3 was significantly correlated with poor clinical outcome (p=0.045 and p=0.007, respectively). Conclusions Our data suggest that downregulation of DSC1-3 may be explained by DNA methylation, DSC1 may be a marker for tumour differentiation, DSC3 has a potential diagnostic value in subclassification of non-small cell lung carcinoma into SCC and ADC, and furthermore, DSC1 and DSC3 may be prognostic markers for lung cancer.