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Methylthioadenosine phosphorylase represents a predictive marker for response to adjuvant interferon therapy in patients with malignant melanoma
Author(s) -
Meyer Stefanie,
Wild Peter J.,
Vogt Thomas,
Bataille Frauke,
Ehret Christoph,
Gantner Susanne,
Landthaler Michael,
KlinkhammerSchalke Monika,
Hofstaedter Ferdinand,
Bosserhoff Anja K.
Publication year - 2010
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.1600-0625.2010.01072.x
Subject(s) - melanoma , stat1 , medicine , immunohistochemistry , interferon , adjuvant therapy , tissue microarray , alpha interferon , stat protein , predictive marker , adjuvant , oncology , clinical significance , cancer research , pathology , cancer , immunology , signal transduction , biology , biochemistry , stat3
Please cite this article as: Methylthioadenosine phosphorylase represents a predictive marker for response to adjuvant interferon therapy in patients with malignant melanoma. Experimental Dermatology 2010; 19 : e251–e257. Abstract: Using tissue microarrays assembling 465 nevi, primary melanomas and metastases, we investigated whether expression of methylthioadenosine phosphorylase (MTAP), a recently suggested biomarker of malignant melanoma, has prognostic significance and may predict responsiveness to adjuvant interferon therapy in patients with melanoma. Because of its association with MTAP activity and interferon signalling pathways, signal transducer and activator of transcription 1 (STAT1) immunohistochemistry was analysed, too. MTAP expression was significantly reduced in melanomas and metastases compared with nevi ( P < 0.001); STAT1 expression significantly increased. In melanomas, loss of MTAP expression was significantly related to Clark level ( P < 0.05) and tumor thickness ( P < 0.01); whereas STAT1 immunoreactivity was significantly related to gender (p < 0.05) and tumor thickness ( P < 0.05). Interestingly, subgroup analysis of patients with a tumor thickness of 1.5–4.0 mm revealed a significant survival benefit from adjuvant interferon treatment regarding recurrence‐free survival (RFS; P < 0.05) if MTAP expression was observed in the primary melanoma. Patients with STAT1‐positive melanomas also tended to benefit from interferon concerning RFS ( P = 0.074) and showed a significant benefit concerning overall survival (OS; P < 0.05). According to Cox analysis, MTAP expression in contrast to STAT1 was an independent positive prognostic marker for RFS and OS. In conclusion, MTAP represents a highly promising immunohistochemical marker for prognosis and interferon response of patients with malignant melanoma.