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Expression of STAT1 and STAT2 in malignant melanoma does not correlate with response to interferon-alpha adjuvant therapy

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Abstract

Interferon-alpha (IFN-α) is used as an adjuvant therapy in patients with malignant melanoma and who have undergone surgical resection of high-risk lesions. Defective expression or activation of STAT1 or STAT2 has been shown to correlate with IFN-α or resistance in vitro; however, recent data from our laboratory suggest that the anti-tumor effects of IFN-α are dependent on STAT1 signaling within host immune cells. We measured STAT1 and STAT2 expression in 28 melanoma biopsies (8 cutaneous lesions; 1 lung metastasis; 19 nodal metastases) obtained from patients prior to the initiation of adjuvant IFN-α therapy. Disease recurrence following IFN-α treatment did not correlate with the staining intensity of either STAT1 (P=0.61) or STAT2 (P=0.52). Tumors with minimal STAT1 or STAT2 expression (<20% positive) were present in four patients with tumor-positive lymph nodes, who exhibited prolonged relapse-free survival (>44 months) following adjuvant therapy. Conversely, high levels of STAT1 were present in a patient who recurred during the course of IFN-α therapy. A case study of one patient who experienced recurrent disease during IFN-α treatment revealed that STAT1 levels were greater in the recurrent tumor when compared to the original lesion. These studies provide direct evidence to suggest that levels of STAT1 and STAT2 within the tumor do not influence a patient’s response to adjuvant IFN-α.

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Abbreviations

IFN-α:

Interferon-alpha

IFN-α2b:

Interferon-alpha 2b

STAT:

Signal transducer and activator of transcription

H & E:

Hematoxylin and eosin

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Acknowledgements

The authors thank Patrick Roche and The Ohio State University Histology Core Facility for assistance in optimizing immunohistochemical staining. We also thank Judith Bowers for her help in the management of clinical data. This work was supported by National Institutes of Health (NIH) Grants CA84402, P30-CA16058, The Valvano Foundation for Cancer Research Award, and The Ohio State University Department of Surgery Clinical Science Seed Grant. GBL is a NRSA T32 fellow (5 T32 CA90223-02). The Tissue Procurement Shared Resource of the Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio is supported in part by NIH Grant P30 CA16059.

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Authors and Affiliations

  1. Division of Human Cancer Genetics, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Columbus, OH, 43210, USA

    Gregory B. Lesinski, Daniel Valentino & William E. Carson III

  2. Center for Biostatistics, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Columbus, OH, 43210, USA

    Erinn M. Hade

  3. Department of Pathology, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Columbus, OH, 43210, USA

    Susie Jones, Cynthia Magro & Abhik Ray Chaudhury

  4. Department of Surgery, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Columbus, OH, 43210, USA

    Michael J. Walker & William E. Carson III

  5. Division of Surgical Oncology, The Ohio State University, N924 Doan Hall, 410 W. 10th Ave, Columbus, OH, 43210, USA

    William E. Carson III

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  1. Gregory B. Lesinski
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  2. Daniel Valentino
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  8. William E. Carson III
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Correspondence to William E. Carson III.

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Lesinski, G.B., Valentino, D., Hade, E.M. et al. Expression of STAT1 and STAT2 in malignant melanoma does not correlate with response to interferon-alpha adjuvant therapy. Cancer Immunol Immunother 54, 815–825 (2005). https://doi.org/10.1007/s00262-004-0649-y

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  • DOI: https://doi.org/10.1007/s00262-004-0649-y

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