title: Co-expression of cancer testis antigens and topoisomerase 2-alpha in triple negative breast carcinomas.
abstract: Triple negative breast cancers (TNBC) are characterized by aggressive tumor biology, lack of targeted treatments and poor prognosis. Anthracyclins were shown to induce immunogenic death in target cells, potentially leading to "endogenous" vaccination. We comparatively assessed expression of cancer testis antigens (CTA) and topoisomerase 2-alpha (TOPO2A), a well defined molecular target of anthracyclins, in TNBC fully characterized for basal-like (BL) immunophenotype, BL morphology and conventional clinicopathological factors. The study included 83 patients undergoing surgery between January 2003 and December 2009. Tissue sections were stained with CK5/6, CK14, EGFR, Ki-67, TOPO2A, MAGE-A1, MAGE-A10, NY-ESO and multi-MAGE-A specific reagents. Of the 83 TNBC, >66.3% had BL immunophenotype and 48.2% had BL morphology. MAGE-A1 specific staining was most frequently detectable (69.2%), followed by multi-MAGE-A (58%), NY-ESO (27.1%) and MAGE-A10 (16%) specific staining. MAGE-A10 expression significantly correlated with tumor size (p=0.026). Furthermore, MAGE-A1, MAGE-A10 and multi-MAGE-A specific stainings significantly correlated with advanced clinical stage (p=0.024, p=0.041, p=0.031, respectively). We found no significant association between CTA expression and disease free (DFS) or overall survival (OS). Most interestingly, a significant correlation was observed between expression of MAGE-A10 and NY-ESO and expression of TOPO2A (p=0.005, p=0.013). Expression of defined CTA and TOPO2A are significantly correlated in TNBC. Considering the limited therapeutic options for TNBC, these findings might suggest novel forms of combination therapies that should be further explored.
authors.affiliation: Department of Pathology, Forensic Medicine and Cytology, Split University Hospital Center, University of Split, School of Medicine, Spinčićeva 1, Split, Croatia. Electronic address: ivana.mrklic@mefst.hr.
authors.forename: Ivana
authors.initials: I
authors.lastname: Mrklić
authors.affiliation: Department of Surgery, Research Laboratory, University Hospital Basel, Basel, Switzerland.
authors.forename: Giulio Cesare
authors.initials: GC
authors.lastname: Spagnoli
authors.affiliation: Department of Oncology, Zagreb University Hospital Center, University of Zagreb, School of Medicine, Kispatićeva 12, Zagreb, Croatia.
authors.forename: Antonio
authors.initials: A
authors.lastname: Juretić
authors.affiliation: Department of Pediatric Surgery, Split University Hospital Center, University of Split, School of Medicine, Spinčićeva 1, Split, Croatia.
authors.forename: Zenon
authors.initials: Z
authors.lastname: Pogorelić
authors.affiliation: Department of Pathology, Forensic Medicine and Cytology, Split University Hospital Center, University of Split, School of Medicine, Spinčićeva 1, Split, Croatia.
authors.forename: Snježana
authors.initials: S
authors.lastname: Tomić
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D018270:Carcinoma, Ductal, Breast / Q000503:physiopathology*; D004250:DNA Topoisomerases, Type II / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D064726:Triple Negative Breast Neoplasms / Q000503:physiopathology*
chemical_list: D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D004250:DNA Topoisomerases, Type II
keywords: Basal like breast cancer; Cancer testis antigens; Combination treatments; Human; Topoisomerase 2-alpha; Triple negative breast cancer