Article


Expression of the cancer/testis antigen NY-ESO-1 in primary and metastatic malignant melanoma (MM) - correlation with prognostic factors

Elsa F. Velazquez1,2,3*, Achim A. Jungbluth4*, Molly Yancovitz1, Sacha Gnjatic4, Sylvia Adams5, David O'Neill5, Kira Zavilevich5, Tatyana Albukh5, Paul Christos6, Madhu Mazumdar6, Anna Pavlick1,7, David Polsky1, Richard Shapiro7, Russell Berman7, Joanna Spira1, Klaus Busam8, Iman Osman1,5 and Nina Bhardwaj1,2,5*

1Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, NY, USA

2Department of Pathology, New York University School of Medicine, New York, NY, USA

3Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA

4Ludwig Institute for Cancer Research, New York, NY, USA

5Department of Medicine, New York University School of Medicine, New York, NY, USA

6Department of Public Health, Weill Medical College of Cornell University, New York, NY, USA

7Department of Surgery, New York University School of Medicine, New York, NY, USA

8Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

*These authors contributed equally to this work

Contributed by: LJ Old

Keywords: human, melanoma, NY-ESO-1, immunohistochemistry, prognosis


Abstract

Cancer/testis (CT) antigens are potential targets for cancer immunotherapy, with NY-ESO-1 being among the most immunogenic. In several clinical trials in malignant melanoma (MM) patients, NY-ESO-1 protein/peptides showed clear evidence of inducing specific immunity. However, little is known about NY-ESO-1 expression in primary and metastatic MM and its relationship to disease progression. We analyzed NY-ESO-1 expression immunohistochemically in a series of primary and metastatic MMs and its relation to prognostic parameters and survival. We studied 61 primary and 63 metastatic MM specimens (from 61 and 56 patients, respectively). The prevalence of NY-ESO-1 expression was significantly higher in metastatic versus primary tumors [18/56 (32%) versus 8/61 (13%), P = 0.015]. There was a significant association between initial stage at presentation and NY-ESO-1 expression [stage I (3.45%), stage II (9.52%) and stage III (45.45%), P = 0.0014]. Primary MMs expressing NY-ESO-1 were significantly thicker than NY-ESO-1 negative cases (median thickness 4.7 mm versus 1.53 mm respectively, P = 0.03). No significant difference was seen in overall survival. In conclusion, NY-ESO-1 is more frequently expressed in metastatic than in primary MM and its expression is associated with thicker primary lesions and a higher frequency of metastatic disease, indicative of a worse prognosis. Our study suggests that patients with metastatic MM who express NY-ESO-1 may benefit from NY-ESO-1-based immunotherapy.