B54
Expression of high molecular weight tenascin-C isoforms is associated with breast carcinomas in young women
David Guttery1, Rachael Hancox1, Sinead Lambe1, J Howard Pringle1, Rosemary Walker1, J Louise Jones2, Jacqueline Shaw1
1University of Leicester, UK, 2Cancer Research UK Clinical Cancer Centre, London, UK
Tenascin-C (TNC) is an extracellular matrix glycoprotein expressed at low levels in normal breast tissue and higher levels in both the stroma and malignant cells of solid tumours. Multiple isoforms of TNC are generated by alternative splicing. The aim of this study was to investigate the expression of key high molecular weight (MW) TNC isoforms containing domains D, B/D, AD1 and AD2 in breast cancers. Quantitative real-time PCR using specific TaqMan Assays for total TNC, exons 9/16, 14/16, AD1 and AD2 was applied to 10 breast cell lines, isolated normal breast myoepithelial cells and fibroblasts and 134 malignant breast samples and expression related to histopathological features.
Total TNC and exons AD1, AD2, 9/16 and 14/16 were detected in 7/10 breast cell lines and isolated myoepithelial cells and fibroblasts. Total TNC and exons 9/16 and 14/16 were detected in the majority of invasive carcinomas with AD1 and AD2 detected at lower frequencies (31% and 23% respectively, with 14% showing co-expression). In the carcinomas, expression of all high MW TNC isoforms was significantly associated with younger patient age (≤ 40 years; p = < 0.05). AD1 and co-expression of AD1 and AD2 was associated with negative ER status (p = 0.011 and 0.032 respectively) and high grade (p = 0.017 and 0.019 respectively). Furthermore, the majority of cases showing high TNC isoform expression were from younger women aged 26 35.
These data show that expression of high MW TNC isoforms is associated with breast carcinomas in young women confirming, as in other studies, that cancers in this age group exhibit important biological differences. The results also confirm that the epithelium is an important source of TNC. However, further analysis of high MW TNC isoform expression in a larger cohort is required to fully evaluate its prognostic significance.
