Loss of beta-catenin expression associated with disease progression in malignant melanoma.
BACKGROUND
beta-catenin plays a crucial role in the function of cell adhesion molecules and also participates in growth regulatory signalling pathways that may be involved in malignant transformation.


OBJECTIVE
To examine beta-catenin expression in lesions of melanocytic origin for associations with clinicopathological markers of disease progression and for its significance as a predictor of disease recurrence and prognosis.


METHODS
beta-catenin expression was examined by immunoperoxidase staining in 50 melanocytic naevi and 91 primary and 50 metastatic melanomas.


RESULTS
beta-catenin was expressed in 96% of melanocytic naevi, in 94% and 65%, respectively, of radial and vertical growth phase primary melanomas, and in 38% of metastatic melanomas. Benign and malignant melanocytic lesions had distinct patterns of beta-catenin localization. Most lesions expressing beta-catenin exhibited cytoplasmic staining; however, over 40% of benign lesions also displayed nuclear staining, which was present only in 10% of primary and 15% of metastatic melanomas. Absent or weak expression of beta-catenin in primary melanomas was associated with several markers of disease progression, including tumour thickness and presence of lymph node metastases. A similar but not statistically significant trend was observed for the association of beta-catenin expression with disease recurrence and prognosis.


CONCLUSIONS
These results suggest that loss or downregulation of beta-catenin expression in melanoma cells plays a significant role in progression of the disease.
Kageshita
T
T
Department of Dermatology, Kumamoto University School of Medicine, 1-1 Honjo, Kumamoto 860-0811, Japan. toshiro@kaiju.medic.kumamoto-u.ac.jp
Hamby
C V
CV
Ishihara
T
T
Matsumoto
K
K
Saida
T
T
Ono
T
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002648:Child; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary; D016015:Logistic Models; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000556:secondary; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D014067:Tonsillar Neoplasms / Q000378:metabolism / Q000556:secondary; D015534:Trans-Activators; D051176:beta Catenin
D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin