Yoon Jin Cha1, Soong June Bae2, Dooreh Kim2, Sung Gwe Ahn2, Joon Jeong2, Ja Seung Koo3, Tae-Kyung Yoo4, Woo-Chan Park4, Ahwon Lee5, Chang Ik Yoon4. 1. Department of Pathology, Gangnam Severance Hospital, College of Medicine, Yonsei University, Seoul, South Korea. 2. Department of Surgery, Gangnam Severance Hospital, College of Medicine, Yonsei University, Seoul, South Korea. 3. Department of Pathology, Severance Hospital, College of Medicine, Yonsei University, Seoul, South Korea. 4. Division of Breast Surgery, Department of Surgery, College of Medicine, Seoul St Mary's Hospital, The Catholic University of Seoul, Seoul, South Korea. 5. Department of Pathology, Seoul St Mary's Hospital, College of Medicine, The Catholic University of Seoul, Seoul, South Korea.
Abstract
BACKGROUND: Yes-associated protein 1 (YAP1) is a transcription factor regulated by the Hippo pathway and functions as an oncogene in various solid tumors under dysregulated Hippo pathway. However, the role of YAP1 in breast cancer remains controversial. Here, we investigated the impact of different levels of nuclear YAP1 expression on the clinical characteristics and survival outcome in patients with breast cancer. PATIENTS AND METHODS: Retrospectively obtained 455 breast tumor samples at Gangnam Severance Hospital were examined for YAP1 expression by immunohistochemistry, and the clinical data were analyzed. External validation was performed using a retrospective cohort and tissues in 482 patients from Severance Hospital. RESULTS: High nuclear YAP1 expression was associated with hormone receptor negativity and aggressive tumor behavior, including lymph node metastasis, high Ki67 labeling index and inferior distant metastasis-free survival (DMFS, hazard ratio [HR] 2.271, 95% confidence intervals [CIs] 1.109-4.650, P = 0.0249), and also confirmed inferior disease free survival (HR 3.208, 95% CIs 1.313-7.833, P = 0.0105) in external validation cohort. In patients with triple-negative breast cancer (TNBC), high nuclear YAP1 expression was an independent significant determinant of poor DMFS (HR 2.384, 95% CIs 1.055-5.386, P = 0.0367). CONCLUSION: Our findings suggest that nuclear YAP1 expression is a biomarker of adverse prognosis and a potential therapeutic target in patients with breast cancer, especially in TNBC.
BACKGROUND: Yes-associated protein 1 (YAP1) is a transcription factor regulated by the Hippo pathway and functions as an oncogene in various solid tumors under dysregulated Hippo pathway. However, the role of YAP1 in breast cancer remains controversial. Here, we investigated the impact of different levels of nuclear YAP1 expression on the clinical characteristics and survival outcome in patients with breast cancer. PATIENTS AND METHODS: Retrospectively obtained 455 breast tumor samples at Gangnam Severance Hospital were examined for YAP1 expression by immunohistochemistry, and the clinical data were analyzed. External validation was performed using a retrospective cohort and tissues in 482 patients from Severance Hospital. RESULTS: High nuclear YAP1 expression was associated with hormone receptor negativity and aggressive tumor behavior, including lymph node metastasis, high Ki67 labeling index and inferior distant metastasis-free survival (DMFS, hazard ratio [HR] 2.271, 95% confidence intervals [CIs] 1.109-4.650, P = 0.0249), and also confirmed inferior disease free survival (HR 3.208, 95% CIs 1.313-7.833, P = 0.0105) in external validation cohort. In patients with triple-negative breast cancer (TNBC), high nuclear YAP1 expression was an independent significant determinant of poor DMFS (HR 2.384, 95% CIs 1.055-5.386, P = 0.0367). CONCLUSION: Our findings suggest that nuclear YAP1 expression is a biomarker of adverse prognosis and a potential therapeutic target in patients with breast cancer, especially in TNBC.
Authors: Woojin Jeong; Sang-Bae Kim; Bo Hwa Sohn; Yun-Yong Park; Eun Sung Park; Sang Cheol Kim; Sung Soo Kim; Randy L Johnson; Michael Birrer; David S L Bowtell; Gordon B Mills; Anil Sood; Ju-Seog Lee Journal: Anticancer Res Date: 2014-02 Impact factor: 2.480
Authors: Peter Schmid; Sylvia Adams; Hope S Rugo; Andreas Schneeweiss; Carlos H Barrios; Hiroji Iwata; Véronique Diéras; Roberto Hegg; Seock-Ah Im; Gail Shaw Wright; Volkmar Henschel; Luciana Molinero; Stephen Y Chui; Roel Funke; Amreen Husain; Eric P Winer; Sherene Loi; Leisha A Emens Journal: N Engl J Med Date: 2018-10-20 Impact factor: 91.245
Authors: Antonio C Wolff; M Elizabeth Hale Hammond; Kimberly H Allison; Brittany E Harvey; Pamela B Mangu; John M S Bartlett; Michael Bilous; Ian O Ellis; Patrick Fitzgibbons; Wedad Hanna; Robert B Jenkins; Michael F Press; Patricia A Spears; Gail H Vance; Giuseppe Viale; Lisa M McShane; Mitchell Dowsett Journal: J Clin Oncol Date: 2018-05-30 Impact factor: 44.544