A splice variant of HER2 corresponding to herstatin is expressed in the non-cancerous breast and in breast carcinomas

• Published in: Neoplasia (New York, N.Y.) N.Y.), 2008-07, Vol.10 (7)
• Main Authors: Koletsa, T, Kostopoulos, I, Charalambous, E, Christoforidou, B, Nenopoulou, E, Kotoula, V
• Format: Article
• Language: English
• ISSN: 1522-8002

Herstatin (HST) is an alternatively spliced HER2 product with growth inhibitory properties in experimental cancer systems. The role of HST in adult human tissues and disease remains unexplored. Here, we investigated HST expression at the mRNA and protein (immunohistochemistry [IHC]) level in parallel with parameters reflecting HER activation in 187 breast carcinomas and matched non-cancerous breast tissues (NCBT). NCBTs demonstrated the highest HST/HER2 transcript ratios corresponding to a few positive epithelial and stromal cells by IHC. Although HST/HER2 transcript ratios in tumors were inversely associated with HER2 IHC grading (p=0.0048 for HER2 IHC-1+ and p=0.0006 for HER2 IHC-2+ vs HER2 negative tumors), relative HST expression within the same tumor/NCBT system remained constant. HST/HER2 ratios did not predict the presence of HST protein, which was found in 46/187 (25%) tumors. A subgroup of HER2 IHC-3+ tumors exhibited high HST/HER2 transcript ratios, strong HST protein positivity, as well as cytoplasmic phosphoAkt/PKB and p21CIP1/WAF1 localization. In conclusion, HST may act as a paracrine factor in the adult breast. Since HST is described as an endogenous pan-HER inhibitor, the presence of this protein in breast carcinomas may portent the inefficiency of exogenous efforts to block HER2 dimerization, while its absence may justify such interventions.