Clinicopathologic significance of dysadherin expression in cutaneous malignant melanoma: immunohistochemical analysis of 115 patients.
BACKGROUND
The E-cadherin-mediated cell adhesion system is frequently inactivated by multiple mechanisms and is involved in tumor progression in many types of cancer. Recently, the authors reported a novel cell membrane glycoprotein, dysadherin, which has an anti-cell-cell adhesion function and down-regulates E-cadherin.


METHODS
Expression of both dysadherin and E-cadherin was investigated immunohistochemically in 115 patients with cutaneous malignant melanoma to determine the correlation between the 2 molecules and their associations with both patient survival and the clinicopathologic features of the tumors.


RESULTS
Dysadherin and E-cadherin were expressed at the cell membranes of melanoma cells. Fifty-two percent of the tumors showed dysadherin immunopositivity, and 91% of the tumors showed reduced E-cadherin immunopositivity. There was no significant inverse correlation between dysadherin expression and E-cadherin expression. Increased dysadherin expression was significantly correlated with nodular subtype (P = 0.042), Clark level (P < 0.001), tumor thickness (P < 0.001), ulceration (P = 0.008), lymph node metastasis (P < 0.001), high TNM classification (P < 0.001), and poor patient survival (P < 0.001). Multivariate analysis of patient survival revealed that increased dysadherin expression was a significant predictor of poor survival (P < 0.001).


CONCLUSIONS
Thus, increased expression of dysadherin was a significant indicator of poor prognosis in patients with cutaneous malignant melanoma.
Nishizawa
Aya
A
Pathology Division, National Cancer Center Research Institute, Tokyo, Japan.
Nakanishi
Yukihiro
Y
Yoshimura
Kimio
K
Sasajima
Yuko
Y
Yamazaki
Naoya
N
Yamamoto
Akifumi
A
Hanada
Katsumi
K
Kanai
Yae
Y
Hirohashi
Setsuo
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D015820:Cadherins / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D007473:Ion Channels; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008840:Microfilament Proteins; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D015996:Survival Rate
D014408:Biomarkers, Tumor; D015820:Cadherins; C451410:FXYD5 protein, human; D007473:Ion Channels; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D009363:Neoplasm Proteins