Cancer testis antigens and NY-BR-1 expression in primary breast cancer: prognostic and therapeutic implications

Abstract

BackgroundCancer–testis antigens (CTA) comprise a family of proteins, which are physiologically expressed in adult human tissues solely in testicular germ cells and occasionally placenta. However, CTA expression has been reported in various malignancies. CTAs have been identified by their ability to elicit autologous cellular and or serological immune responses, and are considered potential targets for cancer immunotherapy. The breast differentiation antigen NY-BR-1, expressed specifically in normal and malignant breast tissue, has also immunogenic properties. Here we evaluated the expression patterns of CTAs and NY-BR-1 in breast cancer in correlation to clinico-pathological parameters in order to determine their possible impact as prognostic factors.MethodsThe reactivity pattern of various mAbs (6C1, MA454, M3H67, 57B, E978, GAGE #26 and NY-BR-1 #5) were assessed by immunohistochemistry in a tissue micro array series of 210 randomly selected primary invasive breast cancers in order to study the diversity of different CTAs (e.g. MAGE-A, NY-ESO-1, GAGE) and NY-BR-1. These expression data were correlated to clinico-pathological parameters and outcome data including disease-free and overall survival.ResultsExpression of at least one CTA was detectable in the cytoplasm of tumor cells in 37.2% of the cases. NY-BR-1 expression was found in 46.6% of tumors, respectively. Overall, CTA expression seemed to be linked to adverse prognosis and M3H67 immunoreactivity specifically was significantly correlated to shorter overall and disease-free survival (p=0.000 and 0.024, respectively).ConclusionsOur findings suggest that M3H67 immunoreactivity could serve as potential prognostic marker in primary breast cancer patients. The exclusive expression of CTAs in tumor tissues as well as the frequent expression of NY-BR-1 could define new targets for specific breast cancer therapies.

Immunohistochemistry in Undifferentiated Neoplasm/Tumor of Uncertain Origin

“…Its expression in breast carcinomas was reported as 58.4% by Woodard et al 86 and 46.6% by Balafoutas et al 87 However, NY-BR-1 expression is strongly associated with ER expression in both studies. In ER À breast carcinomas, NY-BR-1 expression was reported to be as low as 18% and 28.4%, respectively.…”

Microarray expression profiling of dysregulated long non-coding RNAs in triple-negative breast cancer

“…[45][46][47] ANKRD30A is currently one of the most used DTC markers 48 , and one of the potential targets for BC immunotherapy. 29,49 LINC00993 is located approximately 70 Kbp downstream from ANKRD30A and is therefore the nearest non-coding RNA to this gene. LINC00993 is a novel intergenic lncRNA and is also known as lncRNA1188-3, TCONS_l2_00003938, lnc-ANKRD30A-2, RP11-20F24.4, OTTHUMG00000017971.1 or ENSG00000235687.…”

Application of Immunohistochemistry in Breast Pathology: A Review and Update

“…[135][136][137][138]141,142 In ER À breast CAs, its expression was reported as much lower, 18% by Woodard et al 141 and 28.4% by Balafoutas et al 142 In normal tissues, NY-BR-1 expression was noted exclusively in mammary gland epithelia [135][136][137][138]141,142 ; reactivities in skin adnexal structures 140 as well as focal, weak staining in Barrett esophagus and benign mucosal glands of the stomach were also noted. 141 In other tumors studied, NY-BR-1 expression was noted in 27% (3 of 11) of sweat gland carcinomas, 138 75% (18 of 24) of mammary Paget disease, 81% (21 of 26) of extramammary Paget disease, 140 5.6% (8 of 142) of müllerian carcinomas, and 7% (1 of 15) of pancreatic tumors.…”

“…Since then, studies were undertaken to explore NY-BR-1 protein expression in normal and tumor tissues. [135][136][137][138][139][140][141][142] The immunostaining pattern was described as mainly cytoplasmic with focal nuclear staining. In invasive breast CAs, NY-BR-1 expression was reported in 46.6% to …”