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Tissue microarray‐based analysis shows phospho‐β‐catenin expression in malignant melanoma is associated with poor outcome
Author(s) -
Kielhorn Eric,
Provost Elayne,
Olsen Drew,
D'Aquila Thomas G.,
Smith Bradley L.,
Camp Robert L.,
Rimm David L.
Publication year - 2002
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10893
Subject(s) - melanoma , tissue microarray , catenin , microarray , microarray analysis techniques , oncology , cancer research , expression (computer science) , medicine , biology , pathology , gene expression , immunohistochemistry , genetics , wnt signaling pathway , gene , computer science , programming language
Beyond depth of invasion, there are very few prognostic markers to predict outcome in melanoma. It has been shown recently that the β‐catenin oncogene is mutated or shows altered subcellular localization suggesting that activation of β‐catenin mediated signaling plays a role in oncogenesis. We hypothesize that assessment of activated β‐catenin, as detected by a phospho‐specific antibody, may be useful to predict outcome in melanoma. We use immuno‐histochemical analysis of β‐catenin and phospho‐β‐catenin, first to verify the specificity of the phospho‐β‐catenin antibody and then to assay expression in a tissue microarray‐based study. The subcellular localization of β‐catenin is membranous in some cases and cytoplasmic and nuclear in others. We validate the specificity of a ser33/37/thr41 phospho‐β‐catenin antibody in transfected cells and show that the expression is almost exclusively localized to the nucleus in both cultured cells and human tissue. Evaluation of both total and phospho‐β‐catenin antibodies showed that cytoplasmic/nuclear staining was more common in primary lesions, whereas nuclear phospho‐β‐catenin was more common in metastatic lesions. High levels of nuclear phospho‐β‐catenin are associated with significantly worse overall survival (51% vs . 25% overall survival at 5 years, p = 0.046). These results suggest that phospho‐specific antibodies to β‐catenin define a unique subset of cases and that monitoring of phospho‐β‐catenin expression may be useful for assessing prognosis in malignant melanoma. © 2002 Wiley‐Liss, Inc.