Immunohistochemical mismatch repair proteins expression as a tool to predict the melanoma immunotherapy response

Ponti,Giovanni; Pellacani,Giovanni; Tomasi,Aldo; Depenni,Roberta; Maccaferri,Monia; Maiorana,Antonio; Orsi,Giulia; Giusti,Francesca; Cascinu,Stefano; Manfredini,Marco

doi:10.3892/mco.2019.1946

Immunohistochemical mismatch repair proteins expression as a tool to predict the melanoma immunotherapy response

Authors:
- Giovanni Ponti
- Giovanni Pellacani
- Aldo Tomasi
- Roberta Depenni
- Monia Maccaferri
- Antonio Maiorana
- Giulia Orsi
- Francesca Giusti
- Stefano Cascinu
- Marco Manfredini
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Affiliations: Division of Clinical Pathology, Department of Surgical, Medical, Dental and Morphological Sciences with Interest in Transplant, Oncological and Regenerative Medicine, University of Modena and Reggio Emilia, I‑41124 Modena, Italy, Division of Dermatology, Department of Surgical, Medical, Dental and Morphological Sciences with Interest in Transplant, Oncological and Regenerative Medicine, University of Modena and Reggio Emilia, I‑41124 Modena, Italy, Department of Oncology and Haematology, University of Modena and Reggio Emilia, I‑41124 Modena, Italy, Department of Pathology, University of Modena and Reggio Emilia, I‑41124 Modena, Italy
Published online on: November 7, 2019 https://doi.org/10.3892/mco.2019.1946
Pages: 3-8
Copyright: © Ponti et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

In difference to other solid malignancies, the identification of biomarkers for the prediction of malignant melanoma (MM) response to immunotherapy is limited. The aim of the current study was to evaluate the immunohistochemical (IHC) expression of MMR proteins in a cohort of MM metastatic patients receiving anti PD‑1 treatments. The therapeutic response of patients was also retrospectively assessed. The cohort of the current study included 14 patients with advanced MM that had received anti PD‑1 from January 2014 to December 2016 (12 males, 2 females; average age, 71 years; age range, 47‑88 years). IHC analysis of MLH1, PMS2, MSH2 and MSH6 proteins was performed on paraffin‑embedded primary tumor samples from each patient and on the 23 available metastasis specimens obtained from the Division of Pathology (University of Modena and Reggio Emilia). The results revealed that 7% of the primary melanoma tissue obtained from the patient cohort exhibited the loss of expression of at least one MMR protein. Three samples from one patient, including one primary melanoma and two metastases, exhibited no MSH6 expression and had the most successful response to anti PD‑1 treatment, with a progression‑free survival and overall survival of 956 and 2,546 days, respectively. In conclusion, the assessment of MMR protein expression represents a potential predictive marker that may have critical importance for patients with primary and metastatic MM, primarily as criterion for the adoption of immunotherapy treatments.

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