Reduced beta-catenin expression in the cytoplasm of advanced-stage superficial spreading malignant melanoma.
OBJECTIVE
The purpose of the present work was to analyze the expression of beta-catenin in a panel of superficial and nodular spreading primary and metastatic melanomas, and to correlate the level of immunohistochemical staining to clinicopathological parameters.


METHODS
Expression of beta-catenin was examined by immunohistochemistry in 106 superficial and 58 nodular spreading primary melanomas, as well as in 66 metastatic lesions.


RESULTS
Membrane-associated staining was detected in nearly all of the cases, and no association to clinical parameters could be revealed. When cytoplasmic localization of the protein was recorded, a significant higher fraction of the superficial than the nodular spreading primary lesions expressed the protein in the majority of the cells (P < 0.0001). Interestingly, metastatic lesions from superficial melanomas demonstrated down-regulated expression of the protein, and in agreement with this a significant inverse correlation between protein expression and the vertical thickness of the primary lesion was detected (P = 0.012). Furthermore, a significant correlation between cytoplasmic localization and disease-free survival (P = 0.0006) was revealed, but beta-catenin did not have any significant impact on overall survival for this group of patients (P = 0.0824). No association was detected between beta-catenin expression and clinicopathological parameters in the nodular subgroup of melanomas, indicating that the protein may play different roles in the malignant progression of the two main types of melanomas.


CONCLUSIONS
In summary, we hypothesize that cytoplasmic beta-catenin has a protective role in early melanoma development.
Maelandsmo
Gunhild M
GM
Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway. g.m.maelandsmo@labmed.uio.no
Holm
Ruth
R
Nesland
Jahn M
JM
Fodstad
Øystein
Ø
Flørenes
Vivi Ann
VA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D019938:Cyclin D1 / Q000096:biosynthesis; D050760:Cyclin-Dependent Kinase Inhibitor p27; D003593:Cytoplasm / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000096:biosynthesis* / Q000378:metabolism; D018572:Disease-Free Survival; D006801:Humans; D007150:Immunohistochemistry; D008545:Melanoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012008:Recurrence; D012878:Skin Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D013997:Time Factors; D015534:Trans-Activators / Q000096:biosynthesis* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis; D051176:beta Catenin
C495270:CTNNB1 protein, human; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D051176:beta Catenin; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27