title: RB1CC1 together with RB1 and p53 predicts long-term survival in Japanese breast cancer patients.
abstract: RB1-inducible coiled-coil 1 (RB1CC1) plays a significant role in the enhancement of the retinoblastoma tumor suppressor (RB1) pathway and is involved in breast cancer development. However, RB1CC1's role in clinical progression of breast cancer has not yet been evaluated, so, as a first step, it is necessary to establish its usefulness as a tool to evaluate breast cancer patients. In this report, we have analyzed the correlation between abnormalities in the RB1CC1 pathway and long-term prognosis, because disease-specific death in later periods (>5 years) of the disease is a serious problem in breast cancer. Breast cancer tissues from a large cohort in Japan were evaluated by conventional immunohistochemical methods for the presence of the molecules involved in the RB1CC1 pathway, including RB1CC1, RB1, p53, and other well-known prognostic markers for breast cancer, such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. The correlation between the immunohistochemical results and clinical outcomes of 323 breast cancer patients was analyzed using a Kaplan-Meier log-rank test and a multivariate Cox proportional hazards regression analysis. Absence of nuclear RB1CC1 expression was associated with the worst prognosis (Log-rank test, Chi-Square value = 17.462, p<0.0001). Dysfunction of either one of RB1CC1, RB1, or p53 was associated with the highest risk for cancer-specific death, especially related to survival lasting more than 5 years (multivariate Cox proportional hazard ratio = 3.951, 95% Confidence Interval =1.566-9.967, p = 0.0036). Our present data demonstrate that the combined evaluation of RB1CC1, RB1 and p53 by conventional immunohistochemical analysis provides an accurate prediction of the long-term prognoses of breast cancer patients, which can be carried out as a routine clinical examination.
authors.affiliation: Department of Clinical Laboratory Medicine, Shiga University of Medical Science, Otsu, Japan. chano@belle.shiga-med.ac.jp
authors.forename: Tokuhiro
authors.initials: T
authors.lastname: Chano
authors.forename: Kaichiro
authors.initials: K
authors.lastname: Ikebuchi
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tomita
authors.forename: Yufen
authors.initials: Y
authors.lastname: Jin
authors.forename: Hideo
authors.initials: H
authors.lastname: Inaji
authors.forename: Makoto
authors.initials: M
authors.lastname: Ishitobi
authors.forename: Koji
authors.initials: K
authors.lastname: Teramoto
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Ochi
authors.forename: Hitosuke
authors.initials: H
authors.lastname: Tameno
authors.forename: Ichiro
authors.initials: I
authors.lastname: Nishimura
authors.forename: Kahori
authors.initials: K
authors.lastname: Minami
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Inoue
authors.forename: Takahiro
authors.initials: T
authors.lastname: Isono
authors.forename: Masao
authors.initials: M
authors.lastname: Saitoh
authors.forename: Taketoshi
authors.initials: T
authors.lastname: Shimada
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Hisa
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Okabe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000071183:Autophagy-Related Proteins; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D002467:Cell Nucleus / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007564:Japan; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics*; D016160:Retinoblastoma Protein / Q000096:biosynthesis*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
chemical_list: D000071183:Autophagy-Related Proteins; C407704:RB1CC1 protein, human; D016160:Retinoblastoma Protein; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D011505:Protein-Tyrosine Kinases