Tissue microarray analysis of methylthioadenosine phosphorylase protein expression in melanocytic skin tumors.
BACKGROUND
Using tissue microarrays, we investigated whether methylthioadenosine phosphorylase (MTAP) protein expression is associated with clinicopathologic variables in benign and malignant melanocytic skin tumors.


METHODS
Cytoplasmic MTAP expression was detected in 227 (72.1%) of 315 informative cases. Expression was significantly reduced in primary malignant melanomas and in melanoma metastases compared with benign nevi (P<.001 for both). No difference was noted in MTAP expression between primary malignant melanomas and melanoma metastases. In primary malignant melanomas, a Ki67-labeling index less than 5% was associated with MTAP expression (P = .04), suggesting that loss of MTAP expression is associated with proliferation. No other variables had significant associations with MTAP expression. Lymph node metastases demonstrated significantly higher MTAP expression compared with skin metastases (P = .01). In the overall cohort, MTAP expression was not associated with prognosis. Among 26 patients with MTAP-positive melanomas and tumor recurrence, 18 patients who received interferon therapy had a significant benefit compared with 8 patients who did not receive interferon therapy (P = .009). This was not seen in the patients with MTAP-negative tumors. Conclusion Methylthioadenosine phosphorylase protein expression may be a predictive marker of interferon therapy resistance in patients with melanoma and disease progression.
Wild
Peter J
PJ
Institute of Pathology and Department of Dermatology, University of Regensburg, Germany.
Meyer
Stefanie
S
Bataille
Frauke
F
Woenckhaus
Matthias
M
Ameres
Markus
M
Vogt
Thomas
T
Landthaler
Michael
M
Pauer
Armin
A
Klinkhammer-Schalke
Monika
M
Hofstaedter
Ferdinand
F
Bosserhoff
Anja K
AK
D000970:Antineoplastic Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007150:Immunohistochemistry; D007372:Interferons / Q000627:therapeutic use; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D046228:Microarray Analysis; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D011379:Prognosis; D011683:Purine-Nucleoside Phosphorylase / Q000378:metabolism*; D012878:Skin Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D016019:Survival Analysis
D000970:Antineoplastic Agents; D007372:Interferons; D011683:Purine-Nucleoside Phosphorylase; C021784:5'-methylthioadenosine phosphorylase