HER3 Expression in Human Breast Carcinomas Is Associated with Tumor Size, Lymph Node Metastasis and Estrogen Receptor Status.
Cristina Teixido, Vicente Peg, Teresa Moline, Marta Sanchez-Martin, Atanasio Pandiella, Santiago Ramon y Cajal, Javier Hernandez-Losa. Vall Hebron University Hospital, Barcelona, Spain; Center for Cancer investigation, Salamanca, Spain
Background: Estrogen receptor (ER) and progesterone receptor (PR) are crucial pronostic factors in breast cancer. Resistance to anti-estrogens, such as tamoxifen, limits the efficacy of these compounds in ER positive breast cancer and several mechanisms through increased expression of EGFR and/or HER2 have been proposed. Additionally, cross-talk between HER receptors and ER has been described. Here we evaluate HER3 expression in a large series of breast carcinoma and its correlation with both clinicopathological features (histological grade, tumor size, lymph node status) and molecular biomarkers (ER, PR, HER2 and Ki67).
Design: 196 primary breast carcinomas were collected from the archives of the Pathology Department of Vall d'Hebron University Hospital from 2001 to 2008. HER3 immunohistochemistry (IHC) was performed in whole sections from formalin fixed paraffin embedded blocks and cases were evaluated by two independent pathologists as follows: 0 (no expression), 1 (weak expression or moderate staining in <10% of neoplastic cells), 2 (moderate staining in >10% neoplastic cells) and 3 (strong staining). Cases were then considered as positive (if scored 2 or 3) or negative (if scored 0 or 1). Correlation between HER3 membrane staining expression, with usual pathological factors and other conventional biomarkers (ER, PR, HER2 and Ki67) was analyzed using Chi-Square and Kruskal-Wallis statistical tests.
Results: In this series, we showed that HER3 was significantly more expressed in HER2 positive tumors (p=0.037). Moreover, HER3 expression positively correlated with ER staining (p=0.001), tumor size (p=0.001) and lymph node metastasis (p=0.012). Only a trend was observed with histological grade (p=0.053) and no statistical differences were seen with PR or Ki67.
Conclusions: In this study, we show that HER3 expression was higher in HER2 positive tumors. Furthermore, HER3 expression positively correlated with tumor size, lymph node metastasis and ER staining. These results support the hyphotesis that HER3 upregulation may play a role in tumor aggressiveness in HER2 positive, ER positive breast tumors. HER3, dimerizing with HER2 and hyperactivating downstream pathways, may be related to anti-estrogen resistance in this subset of patients. Ongoing studies will elucidate whether HER3 expression positively correlates with Tamoxifen resistance and, if so, whether the addition of anti-HER3 agents has clinical benefit in patients refractory to anti-estrogen therapy.
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 2, Wednesday Afternoon