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Immune biomarkers are more accurate in prediction of survival in ulcerated than in non-ulcerated primary melanomas

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Abstract

Introduction

Ulcerated melanomas may have a unique biology and microenvironment. We test whether markers of immune infiltration correlate with clinical outcome in ulcerated compared to non-ulcerated primary melanoma tumors.

Methods

Sixty-two stage II–III cutaneous melanomas, 32 ulcerated and 30 non-ulcerated, were analyzed for tumor-infiltrating lymphocytes (TILs). Immunohistochemistry (IHC) was performed for CD2, a marker previously shown to correlate with overall survival (OS) and recurrence-free survival (RFS) in this patient population. IHC using antibody, VE1, to BRAF V600E was also performed on a subset of 41 tumors to assess the relationship of BRAF mutation to immune markers.

Results

We found, using Cox regression models, that the presence of TILs was associated with improved OS (p = 0.034) and RFS (p = 0.002) in ulcerated melanoma tumors, but not in non-ulcerated melanoma (p = 0.632, 0.416). CD2 expression also was correlated with improved OS (p = 0.021) and RFS (p = 0.001) in ulcerated melanoma, but no relationship was seen in non-ulcerated melanoma (p = 0.427, 0.682). In this small population, BRAF status did not correlate with TILs or CD2+ count.

Conclusion

Our data show that immune markers including TILs and CD2 count correlate more closely with survival in ulcerated melanomas than that in non-ulcerated melanomas. We propose that immune biomarkers may be particularly relevant to ulcerated, as compared to non-ulcerated, melanomas and that this merits study in larger populations.

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Abbreviations

AJCC:

American Joint Committee on Cancer

Ang-2:

Angiopoietin 2

EORTC:

European Organisation for Research and Treatment of Cancer

FFPE:

Formalin fixed paraffin embedded

GMC:

Geisinger Medical Center

HPF:

High-powered field

IHC:

Immunohistochemistry

IRB:

Institutional review board

ISMMS:

Icahn School of Medicine at Mount Sinai

LFA-3:

Lymphocyte function-associated antigen-3

OS:

Overall survival

RFS:

Recurrence-free survival

TILs:

Tumor-infiltrating lymphocytes

TNBC:

Triple-negative breast cancer

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Acknowledgments

The study was funded by Dermatology Foundation (Career Development Award), American Association for Cancer Research (Landon Cancer Immunology Innovator Award), Herbert Irving Comprehensive Cancer Center at Columbia University, and Tisch Cancer Center at the Icahn School of Medicine at Mount Sinai.

Conflict of interest

The authors have no conflict of interest to declare.

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Author notes

    Authors and Affiliations

    1. Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

      Ellen H. de Moll, Sara H. Perkins, Shira Wieder, Sebastian G. Bernardo, Jerry Chipuk, Miriam B. Birge, Robert G. Phelps & Yvonne M. Saenger

    2. Department of Medicine, Columbia University College of Physicians and Surgeons, 177 Fort Washington Avenue, New York, NY, 10032, USA

      Yichun Fu, Yingzhi Qian & Yvonne M. Saenger

    3. Hematology Oncology Division, Department of Medicine, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

      Sacha Gnjatic, Romain Remark, Marina Moskalenko, Miriam B. Birge, Robert G. Phelps & Yvonne M. Saenger

    4. Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

      Jonathan Yao & Jerry Chipuk

    5. Geisinger Medical Center, Danville, PA, USA

      Tammie Ferringer

    6. Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA

      Rui Chang

    7. Department of Pathology, Columbia University College of Physicians and Surgeons, New York, NY, USA

      Basil A. Horst

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    1. Ellen H. de Moll
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    Correspondence to Yvonne M. Saenger.

    Additional information

    Ellen H. de Moll and Yichun Fu have contributed equally to this article and should be considered co-first authors.

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    de Moll, E.H., Fu, Y., Qian, Y. et al. Immune biomarkers are more accurate in prediction of survival in ulcerated than in non-ulcerated primary melanomas. Cancer Immunol Immunother 64, 1193–1203 (2015). https://doi.org/10.1007/s00262-015-1726-0

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