Loss of Yes-associated protein (YAP) expression is associated with estrogen and progesterone receptors negativity in invasive breast carcinomas

Abstract

Yes-associated protein (YAP) is a well characterized transcriptional coactivator that interacts with various transcription factors and modulates their transcriptional activities. Phosphorylation of YAP by specific kinases regulates its cellular distribution and transcriptional activation functions. Sequestration of phosphorylated YAP in cytoplasm results in the reduction of transcription from its target genes. Since, YAP has been characterized as a coactivator of estrogen (ER) and progesterone (PR) receptors, we examined the immunohistochemical expression profile of YAP and correlation of YAP expression with that of ER and PR in normal (40 samples) and tumor breast (226 samples) from microarray tissue samples using immunohistochemistry. Here we show that YAP expression is significantly reduced in invasive carcinoma samples compared to normal breast tissues, which express high levels of YAP (YAP was positive for 45.1% of invasive carcinoma samples versus 82.5% of normal samples P<0.0001). Furthermore, the data shows that reduced expression of YAP in invasive carcinoma samples is significantly associated with ER negativity (YAP was negative for 59.9% in ER negative versus 38.9% in ER positive invasive carcinoma samples, P=0.007) and PR negativity (YAP was negative for 60.1% in PR negative versus 28.9% in PR positive, P=0.0004). Among invasive carcinoma samples, 42.9% were YAP, ER, and PR negative, whereas only 7.5% were found to be YAP, ER, and PR positive. On the contrary, 20 out of 23 (87%) normal breast tissues that were positive for ER and PR were also positive for YAP. These data suggest that YAP may act as a tumor suppressor in invasive breast carcinomas and it can also be used as a molecular marker for ER and PR negative breast tumors.