MAGE-A10 Protein Expression in Advanced High Grade Serous Ovarian Cancer Is Associated with Resistance to First-Line Platinum-Based Chemotherapy

Nataša Lisica Šikić; Branka Petrić Miše; Snježana Tomić; Giulia Spagnol; Luka Matak; Antonio Juretić; Giulio Spagnoli

doi:10.3390/cancers15194697

MAGE-A10 Protein Expression in Advanced High Grade Serous Ovarian Cancer Is Associated with Resistance to First-Line Platinum-Based Chemotherapy

Cancers (Basel). 2023 Sep 23;15(19):4697. doi: 10.3390/cancers15194697.

Authors

Nataša Lisica Šikić¹, Branka Petrić Miše², Snježana Tomić³, Giulia Spagnol⁴, Luka Matak⁵, Antonio Juretić⁶, Giulio Spagnoli⁷

Affiliations

¹ Department of Pathology, Forensic Medicine and Cytology, General Hospital Zadar, 23000 Zadar, Croatia.
² Department of Oncology, Clinical Hospital Center Split, School of Medicine, University of Split, 21000 Split, Croatia.
³ Department of Pathology, Forensic Medicine and Cytology, Clinical Hospital Center Split, School of Medicine, University of Split, 21000 Split, Croatia.
⁴ Department of Women and Children's Health, Clinic of Gynecology and Obstetrics, University of Padua, 35122 Padua, Italy.
⁵ Department of Obstetrics and Gynecology, General Hospital Zadar, 23000 Zadar, Croatia.
⁶ Department of Oncology, University Hospital Dubrava, University of Zagreb, 10000 Zagreb, Croatia.
⁷ Istituto CNR "Translational Pharmacology", 00133 Rome, Italy.

Abstract

Ovarian cancer has a dismal prognosis. Standard treatment following surgery relies on platinum-based chemotherapy. However, sizeable percentages of patients are unresponsive. Identification of markers predicting the response to chemotherapy might help select eligible patients and spare non-responding patients from treatment-associated toxicity. Cancer/testis antigens (CTAs) are expressed by healthy germ cells and malignant cells of diverse histological origin. This expression profile identifies them as attractive targets for cancer immunotherapies. We analyzed the correlations between expression of MAGE-A10 and New York esophageal-1 cancer (NY-ESO-1) CTAs at the protein level and the effectiveness of platinum-based chemotherapy in patients with advanced-stage high-grade serous ovarian carcinoma (HGSOC). MAGE-A10 and NY-ESO-1 protein expression was analyzed by immunohistochemistry (IHC) in formalin-fixed, paraffin-embedded samples from 93 patients with advanced-stage HGSOC treated at our institutions between January 1996 and December 2013. The correlation between the expression of these markers and response to platinum-based chemotherapy, evaluated according to RECIST 1.1 criteria and platinum sensitivity, measured as platinum-free interval (PFI), progression free (PFS), and overall survival (OS) was explored. The MAGE-A10 protein expression predicted unresponsiveness to platinum-based chemotherapy (p = 0.005), poor platinum sensitivity (p < 0.001), poor PFS (p < 0.001), and OS (p < 0.001). Multivariate analysis identified MAGE-A10 protein expression as an independent predictor of poor platinum sensitivity (p = 0.005) and shorter OS (p < 0.001). Instead, no correlation was observed between the NY-ESO-1 protein expression and response to platinum-based chemotherapy (p = 0.832), platinum sensitivity (p = 0.168), PFS (p = 0.126), and OS (p = 0.335). The MAGE-A10 protein expression reliably identified advanced-stage HGSOC unresponsive to platinum-based chemotherapy. Targeted immunotherapy could represent an important alternative therapeutic option in these cancers.

Keywords: MAGE- A10; NY-ESO-1; immunohistochemistry; ovarian cancer; platinum sensitivity; prognosis; response to platinum-based chemotherapy.

Grants and funding

This research received no external funding.