title: [Claudins as prognostic factors of breast cancer].
abstract: Different expression of claudins and E-cadherin has been described in the pathogenesis and progression of breast cancer. Changes in the expression of these junctional molecules have also been described as being of prominent importance in other cancers as well. Thus, we aimed at exploring the potential prognostic relevance of these cell junctional molecules in breast carcinoma cases. Expression of claudin-1, -3, -4, -5, -7, -8, -10, -15, -18 and E-cadherin at mRNA level was evaluated in correlation with survival in publicly available datasets containing expression measurements of 1809 breast cancer patients. Breast cancer tissues of 636 patients were evaluated with tissue microarray technique and immunohistochemical method for claudin-1, -2, -3, -4, -5, -7 and E-cadherin protein expression. In 96 cases lymph node metastases were also subjects of the study. Claudin expression bears prognostic information in itself. Based on bioinformatic data analysis, the meta-gene of claudin-3, -4, -7 and E-cadherin has proved the most powerful in predicting survival. An immunohistochemical protein profile consisting of claudin-2, -4 and E-cadherin was able to predict outcome in the most effective manner in the training set. Combining the overlapping members of the distinct methods resulted in the CC index (consisting of claudin-4 and E-cadherin, a.k.a. CURIO), which was able to accurately predict relapse-free survival in the validation cohort (p=0.029) in a more efficient way than its components. Cox regression analysis including clinicopathological variables and the average CC score showed that in univariate analysis most of them were prognostic but most of them lost independent prognostic value in multivariate analysis except for the CC index, the subtypes defined by immunoprofiling and vascular invasion. On the other hand, the CC index was able to further refine prognosis splitting good vs. poor prognosis patients into two clusters in these subgroups. Evaluation of lymph node metastases has shown that decreased expression of claudin-1 and elevated expression of claudin-4 can predict worse prognosis in breast cancers spreading to the regional lymph nodes. The defined claudin-cadherin index provides additional prognostic information besides the routinely utilized diagnostic approaches and factors. The level of expression of certain claudins can be of prognostic significance in regional lymph node metastases.
authors.affiliation: Semmelweis Egyetem, Budapest, Hungary. cac@korb2.sote.hu
authors.forename: Marcell A
authors.initials: MA
authors.lastname: Szász
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D062445:Claudin-1 / Q000378:metabolism; D062465:Claudin-3 / Q000378:metabolism; D062506:Claudin-4 / Q000378:metabolism; D062507:Claudin-5 / Q000378:metabolism; D057167:Claudins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008207:Lymphatic Metastasis / Q000175:diagnosis; D011237:Predictive Value of Tests; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D018570:Risk Assessment; D012307:Risk Factors; D015996:Survival Rate; D046888:Tissue Array Analysis; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C568108:CLDN1 protein, human; C491875:CLDN2 protein, human; C568122:CLDN3 protein, human; C568157:CLDN4 protein, human; C107466:CLDN5 protein, human; C473255:CLDN7 protein, human; D015820:Cadherins; D062445:Claudin-1; D062465:Claudin-3; D062506:Claudin-4; D062507:Claudin-5; D057167:Claudins; D012333:RNA, Messenger