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MAGE-A10 PROTEIN EXPRESSION IN ADVANCED HIGH GRADE SEROUS OVARIAN CANCER IS ASSOCIATED WITH RESISTANCE TO FIRST LINE PLATINUM-BASED CHEMOTHERAPY
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  • Luka Matak,
  • Nataša Lisica Šikić,
  • Branka Petrić Miše,
  • Snježana Tomić,
  • Giulia Spagnol,
  • Antonio Juretić,
  • Giulio Spagnoli
Luka Matak
Opca bolnica Zadar

Corresponding Author:[email protected]

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Nataša Lisica Šikić
Opca bolnica Zadar
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Branka Petrić Miše
KBC Split Odjel za onkologijiu i radioterapiju
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Snježana Tomić
Klinicki bolnicki centar Split
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Giulia Spagnol
Azienda Ospedale Universita Padova
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Antonio Juretić
Klinicna bolnica Sveti Duh
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Giulio Spagnoli
Istituto di Farmacologia Traslazionale Consiglio Nazionale delle Ricerche
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Abstract

Objective: 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 response to chemotherapy might help select eligible patients while sparing unresponsive ones treatment-associated toxicity. Cancer/testis antigens (CTA) are expressed by healthy germ cells and malignant cells of diverse histological origin. This expression profile identifies them as attractive targets of cancer immunotherapies. We analyzed correlations between expression of MAGE-A10 and New York esophageal-1 cancer (NY-ESO-1) CTAs at protein level and effectiveness of platinum-based chemotherapy in patients with advanced-stage high-grade serous ovarian carcinoma (HGSOC). Methods: 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. Correlation between expression of these markers and response to platinum-based chemotherapy, evaluated according to RECIST 1.1 criteria, platinum sensitivity, measured as platinum free interval (PFI), progression free (PFS) and overall survival (OS) was explored. Results : MAGE-A10 protein expression predicts unresponsiveness to platinum-based chemotherapy ( p=0.005), poor platinum sensitivity ( p<0.001), and poor PFS ( p<0.001) and OS ( p<0.001). Multivariate analysis identifies MAGE-A10 protein expression as independent predictor of poor platinum sensitivity ( p=0.005) and shorter OS ( p<0.001). Instead, no correlation was observed between 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). Conclusion : MAGE-A10 protein expression reliably identifies advanced-stage HGSOC unresponsive to platinum-based chemotherapy. Targeted immunotherapy could represent an important alternative therapeutic option in these cancers.