Expression of MAGE-C1/CT7 and MAGE-C2/CT10 Predicts Lymph Node Metastasis in Melanoma Patients

Alessandra Curioni-Fontecedro,Burkhardt Seifert,Maries Van Den Broek,Reinhard Dummer,Holger Moch,Alexander Knuth,Davide Soldini,Daniela Mihic-Probst,Natko Nuber

doi:10.1371/journal.pone.0021418

Alessandra Curioni-Fontecedro, Burkhardt Seifert + Show 7 more

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https://doi.org/10.1371/journal.pone.0021418

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Abstract

MAGE-C1/CT7 and MAGE-C2/CT10 are members of the large MAGE family of cancer-testis (CT) antigens. CT antigens are promising targets for immunotherapy in cancer because their expression is restricted to cancer and germ line cells and a proportion of cancer patients presents with immune responses against CT antigens, which clearly demonstrates their immunogenicity. This study investigates the expression of MAGE-C1/CT7 and MAGE-C2/CT10 in primary and metastatic melanoma. Immunohistochemical staining of tissue microarrays that consisted of 59 primary malignant melanomas of the skin, 163 lymph node and distant melanoma metastases and 68 melanoma cell lines was performed. We found MAGE-C1/CT7 expression in 15 out of 50 (24%) primary melanomas and 15 out of 50 (24%) cell lines, whereas MAGE-C2/CT10 was detected in 17 out of 51 (33%) primary melanomas and 14 out of 68 (17%) cell lines. MAGE-C1/CT7 and MAGE-C2/CT10 were both detected in 40% of melanoma metastases. Patients with MAGE-C1/CT7 or MAGE-C2/CT10 positive primary melanoma had significantly more lymph node metastases (p = 0.005 and p<0.001, resp.). Prediction of lymph node metastasis by MAGE-C1/CT7 and MAGE-C2/CT10 was independent of tumor cell proliferation rate (Ki67 labeling index) in a multivariate analysis (p = 0.01). Our results suggest that the expression of MAGE-C1/CT7 and MAGE-C2/CT10 in primary melanoma is a potent predictor of sentinel lymph node metastasis.

Highlights

Melanoma is an aggressive malignant disease with poor prognosis and its incidence is increasing faster than any other cancer
MAGE-C1/CT7 and MAGE-C2/CT10 expression Antibodies specific for MAGE-C1/CT7 and MAGE-C2/CT10 were confirmed on WB with recombinant proteins (Fig. S1)
In this study we demonstrate the expression of MAGE-C1/CT7 and MAGE-C2/CT10 protein in primary melanoma and an increased expression in melanoma metastases

Summary

Introduction

Melanoma is an aggressive malignant disease with poor prognosis and its incidence is increasing faster than any other cancer. Melanoma treatment is an ongoing issue in clinical oncology: For early stage of disease, surgical excision remains the best treatment option whereas adjuvant therapy is not broadly indicated due to unfavorable risk–benefit ratios [2]. In advanced stage of disease, resistance to standard chemotherapy frequently occurs [3,4] and standard immunotherapy shows only moderate success [5] but recently promising data have been shown by blockade of T cell regulatory molecules [6]. Spontaneous, complete regression of melanoma sporadically occurs [7], which presumably is mediated by cancer-specific immunity [8,9,10] and suggests that improvement of immunotherapeutical approaches is worth pursuing. Identification of patients having a high risk of melanoma metastatic spread at the time of diagnosis is crucial in order to detect the subset of patients most likely to benefit from strict follow-up

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