title: New insight on the biological role of p53 protein as a tumor suppressor: re-evaluation of its clinical significance in triple-negative breast cancer.
abstract: While p53 mutation is found in the majority of triple-negative breast cancer (TNBC) and despite recent developments in p53-targeting agents, their therapeutic application is still limited by the absence of standard biomarkers and ambiguousness of its essential biological role in cancer. Whole sections from 305 TNBC cases were stained for p53 to determine the correlation with lymph node metastasis and clinical outcomes in the whole cohort as well as in stratified patient groups according to AJCC stage and the use of adjuvant chemotherapy. Reduced immunohistochemical expression of p53 was an independent risk factor for lymph node metastasis. p53 overexpression was predictive of better clinical outcome in all patients (P = 0.012, disease-free survival and P = 0.008, overall survival) and the stratified cohorts of those who had early breast cancer and received adjuvant chemotherapy. Suppression of endogenous mutant p53 by siRNA and induction of wild-type p53 repressed TNBC cell invasion in vitro. In TNBC, increased immunohistochemical expression of p53 may reflect the accumulation of wild-type p53 rather than the mutant form. Strong p53 protein expression may serve as a favorable prognostic indicator and provide evidence for the use of specific agents targeting p53.
authors.affiliation: Department of Pathology, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Bucheon, Gyeonggi-do, Korea.
authors.forename: Min-Sun
authors.initials: MS
authors.lastname: Jin
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul, Korea.
authors.forename: In Ae
authors.initials: IA
authors.lastname: Park
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul, Korea.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul, Korea.
authors.forename: Yul Ri
authors.initials: YR
authors.lastname: Chung
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Seock-Ah
authors.initials: SA
authors.lastname: Im
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Kyung-Hun
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Surgery, Seoul National University Hospital, Seoul, Korea.
authors.forename: Hyeong-Gon
authors.initials: HG
authors.lastname: Moon
authors.affiliation: Department of Surgery, Seoul National University Hospital, Seoul, Korea.
authors.forename: Wonshik
authors.initials: W
authors.lastname: Han
authors.affiliation: Department of Surgery, Seoul National University Hospital, Seoul, Korea.
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Noh
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul, Korea. karlnash@naver.com.|Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea. karlnash@naver.com.
authors.forename: Han Suk
authors.initials: HS
authors.lastname: Ryu
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D018572:Disease-Free Survival; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Immunohistochemistry; Lymph node metastasis; P53; Triple-negative breast cancer; Tumor suppressive