Claudins 10 and 18 are predominantly expressed in lung adenocarcinomas and in tumors of nonsmokers

Department of Internal Medicine, Respiratory Research Unit, Clinical Research Center, Oulu University Hospital, Finland.
International journal of clinical and experimental pathology (Impact Factor: 1.89). 01/2011; 4(7):667-73.
Source: PubMed


We investigated the expression of claudins 18 and 10 in a large set of primary lung carcinomas.
Immunohistochemical expression of claudin 18 was seen in 12.7 % and claudin 10 in 12.5 % of lung carcinomas. Their expression significantly associated with each other (p<0.001). The expression of claudin 18 and 10 was most prominent in lung adenocarcinomas which displayed positivity in 21.2% and 23.4 % of cases. Female patients had more often claudin 18 and 10 positive tumors, also separately in adenocarcinomas. Interestingly, claudin 10 (p=0.036) and claudin 18 (p=0.001) were more common in tumours of nonsmokers. In adenocarcinomas claudin 18 predicted a better survival (p=0.032). In Cox multivariate analysis, claudin 18 had an independent prognostic value (p=0.027).
The results show that both claudins are most commonly expressed in lung adenocarcinomas and they are more occasionally detected in other histological tumour types. Curiously, female patients and non-smokers express these claudins more commonly suggesting that they may play a part in the carcinogenesis of tobacco unrelated carcinoma. Claudin 18 associated with a better survival in lung adenocarcinoma and had an independent prognostic value and may thus be used in the evaluation of patient prognosis.

Download full-text


Available from: Terttu Harju, Oct 07, 2015
19 Reads
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Tight junctions are structures located in the apicobasal region of the cell membranes. They regulate paracellular solute and electrical permeability of cell layers. Additionally, they influence cellular polarity, form a paracellular fence to molecules and pathogens and divide the cell membranes to apical and lateral compartments. Tight junctions adhere to the corresponding ones of neighbouring cells and by this way also mediate attachment of the cells to one other. Molecules forming the membranous part of tight junctions include occludin, claudins, tricellulin and junctional adhesion molecules. These molecules are attached to scaffolding proteins such as ZO-1, ZO-2 and ZO-3 through which signals are mediated to the cell interior. Expression of tight junction proteins, such as claudins, may be up- or downregulated in cancer and they are involved in EMT thus influencing tumor spread. Like in tumors of other sites, lung tumors show changes in the expression in tight junction proteins. In this review the significance of tight junctions and its proteins in lung cancer is discussed with a focus on the proteins forming the membranous part of these structures.
    International journal of clinical and experimental pathology 01/2012; 5(2):126-36. · 1.89 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: It has been proposed that an epithelial injury may be one of the multiple primary events in the pathogenesis of idiopathic pulmonary fibrosis (IPF). The aim of this study was to characterize the tight junction and adherens junction proteins in normal human lung, IPF, cryptogenic organizing pneumonia, and asbestosis. We determined the immunohistochemical cell-specific expression of tight junction proteins claudin-1, claudin-2, claudin-3, claudin-4, claudin-5, and claudin-7, as well as 3 adherens junction proteins, E-cadherin, N-cadherin, and β-catenin. We further analyzed the expression of claudin-1, claudin-3, and claudin-4 and E-cadherin, N-cadherin, and β-catenin at the transcriptional level by quantitative real-time reverse transcriptase polymerase chain reaction. The expression levels of both tight junction and adherens junction proteins were elevated in regenerative alveolar epithelium in pulmonary fibrosis as compared with the expression of these proteins in normal alveolar epithelium. In particular, the expression levels of claudins-1 and claudin-3 were clearly elevated in all diseases. Furthermore, the amounts of adherens junction proteins messenger RNAs (mRNAs) were also all increased in pulmonary fibroses in comparison with healthy controls, with N-cadherin showing the greatest increase in mRNA levels in all diseases. However, the amounts of claudin-1, claudin-3, and claudin-4 mRNAs in fibrotic lung were similar to or even lower than those measured in the healthy controls. It is possible that the diminished capacity to produce claudin mRNAs may be one explanation for poor repair capacity of alveolar epithelial cells in IPF.
    Human pathology 12/2012; 44(5). DOI:10.1016/j.humpath.2012.08.016 · 2.77 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Understanding the tissue-specific pattern of gene expression is critical in elucidating the molecular mechanisms of tissue development, gene function, and transcriptional regulations of biological processes. Although tissue-specific gene expression information is available in several databases, follow-up strategies to integrate and use these data are limited. The objective of the current study was to identify and evaluate novel tissue-specific genes in human and mouse tissues by performing comparative microarray database analysis and semi-quantitative PCR analysis. We developed a powerful approach to predict tissue-specific genes by analyzing existing microarray data from the NCBI's Gene Expression Omnibus (GEO) public repository. We investigated and confirmed tissue-specific gene expression in the human and mouse kidney, liver, lung, heart, muscle, and adipose tissue. Applying our novel comparative microarray approach, we confirmed 10 kidney, 11 liver, 11 lung, 11 heart, 8 muscle, and 8 adipose specific genes. The accuracy of this approach was further verified by employing semi-quantitative PCR reaction and by searching for gene function information in existing publications. Three novel tissue-specific genes were discovered by this approach including AMDHD1 (amidohydrolase domain containing 1) in the liver, PRUNE2 (prune homolog 2) in the heart, and ACVR1C (activin A receptor, type IC) in adipose tissue. We further confirmed the tissue-specific expression of these 3 novel genes by real-time PCR. Among them, ACVR1C is adipose tissue-specific and adipocyte-specific in adipose tissue, and can be used as an adipocyte developmental marker. From GEO profiles, we predicted the processes in which AMDHD1 and PRUNE2 may participate. Our approach provides a novel way to identify new sets of tissue-specific genes and to predict functions in which they may be involved.
    PLoS ONE 05/2013; 8(5):e64483. DOI:10.1371/journal.pone.0064483 · 3.23 Impact Factor
Show more