Potential for the embryonic morphogen Nodal as a prognostic and predictive biomarker in breast cancer

Tissue sections from 431 therapeutically naive patients diagnosed with benign or malignant breast disease were stained for Nodal by immunohistochemistry and analysed in a blinded manner. The degree of Nodal staining was subsequently correlated with available clinical data, such as diagnoses and disease stage. These tissue findings were further explored in breast cancer cell lines MDA-MB-231 and MDA-MB-468 treated with a Nodal blocking antibody to determine biological effects for target validation.A variable degree of Nodal staining was detected in all samples. The intensity of Nodal staining was significantly greater in undifferentiated, advanced stage, invasive breast cancer compared with benign breast disease or early stage breast cancer. Treatment of human breast cancer cells in vitro with Nodal blocking antibody significantly reduced proliferation and colony-forming ability in soft agar, concomitant with increased apoptosis.These data suggest a potential role for Nodal as a biomarker for disease progression and a promising target for anti-Nodal therapy in breast cancer.Various classification schemes have been developed to categorize the heterogeneity of breast cancer in an attempt to better predict disease stage, progression potential and outcome. Traditionally, the diagnosis of breast cancer has been based on histological criteria [1]. Moreover, defined architectural features like those described in the Nottingham Grading system for invasive breast cancer, which includes tubule formation, mitoses and nuclear pleomorphism, are used to classify the differentiation status of breast cancer - with poor differentiation being the hallmark of high grade, more aggressive disease [2]. Over the years, with advances in molecular medicine, the incorporation of markers, such as oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), have proven to be especially valuable not only for stratifying certain types of breast cancers