DJ-1 as a predictor of pathologic complete remission of neoadjuvant chemotherapy with breast cancer patients.

10544 Background: DJ-1 is a multifunctional protein which is encoded by the causative gene of familial Parkinson disease (i.e., PARK7), and is associated with carcinogenesis. DJ-1 is also a candidate marker for the presence of breast cancer cells, in which it is secreted in nipple fluid and serum. We previously reported that a DJ-1 expression pattern that is low at the protein level and high at the mRNA level is associated with DJ-1 secretion. This secretory expression pattern correlated with a negative hormone receptor status and with unfavorable clinical outcome in breast cancer patients. However, the association of the DJ-1 secretion pattern with therapeutic effect has yet to be determined. Methods: A total of 299 patients received neoadjuvant chemotherapy and surgery from 2002 to 2010 at our institution. We performed immunohistochemistry and in-situ hybridization of DJ-1 in both the needle biopsy and operative specimens of 147 cases with a follow-up time of 3.1 years. The average degree of staining intensity was evaluated semi-quantitatively using an image analyzer. Univariate and multivariate analyses were used to evaluate the predictive value of the therapeutic effect of neoadjuvant chemotherapy. Results: A low expression of DJ-1 protein was detected in the needle biopsy and operative specimens of 89 of the 147 cases, regardless of a high or maintained mRNA level. The tumor response was evaluated as pathological complete remission (pCR) in 39 cases and as non-pCR in the remaining 108 cases. A low expression of DJ-1 protein, which was detected in 34 (87.2%) pCR cases, was a significant predictor on univariate analysis (P <0.001). On multivariate analysis, a low expression of DJ-1 was shown to be a significant independent predictor similar to established predictors such as estrogen receptor status and human epidermal growth factor receptor 2 score. Conclusions: A low expression of DJ-1 protein can serve as a novel and important predictor of a neoadjuvant chemotherapeutic effect, as well as a promising indicator for serologic diagnosis in breast cancer patients.