Abstract P5-06-06: Expression of APOBEC3B in primary breast cancer of Japanese women
Authors: Tokunaga Eriko , Yamashita Nami , Tanaka Kimihiro , Inoue Yuka , Saeki Hiroshi , Oki Eiji , Kitao Hiroyuki , Maehara Yoshihiko 
Published: May 2015

Background: Human cancer genomes contain tens of thousands of mutations. APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) family of cytidine deaminases normally function in innate immune responses that protects against retrovirus and retrotransposon propagation. However, these enzymes can also deaminate cytosines in the host genome and generate C to T mutations. APOBEC3B is overexpressed in several human cancer types, and this overexpression correlates with the pres[not]ence of the APOBEC3B mutation signature. Recent studies have demonstrated APOBEC3B as a source of mutations in various malignancies including breast cancers. However, the relationships between the expression of APOBEC3B in breast cancer and the clinicopathological features have not been fully elucidated.

Aims: To investigate the expression of APOBEC3B mRNA in primary breast cancers and to evaluate the relationships between the APOBEC3B mRNA expression and the clinicopathological characteristics and prognosis in the primary breast cancer of Japanese women.

Methods: Specimens were obtained from 305 patients with primary breast cancers who underwent surgery without neoadjuvant systemic therapy. APOBEC3B mRNA expression was analysed using quantitative reverse transcription-PCR (qRT-PCR). The APOBEC3B expression level was normalized to that of the constitutive housekeeping gene TATA binding protein (TBP). Four breast cancer subtypes were determined by the immunohistochemical analysis of ER, PR and HER2; hormone receptor (HR; ER and/or PR)+/HER2-, HR+/HER2+, HR-/HER2+(HER2) and triple negative (TN).

Results: Expression of APOBEC3B mRNA was detected in 277 tumors, while it was not detected in 28 tumors. The APOBEC3B expression was significantly higher in ER-negative, PR-negative, high grade tumors. The APOBEC3B expression was positively correlated with Ki67 index and highest in TN and lowest in HR+/HER2- subtype. There were no correlations between the APOBEC3B expression and age, tumor size, lymph node metastasis and the stage. The APOBEC3B expression was not statistically different between invasive ductal carcinoma and DCIS, suggesting that the APOBEC3B expression is related to the carcinogenesis of breast cancer. High expression of APOBEC3B was significantly associated with the poor recurrence free survival in all cases and ER-positive cases; however, APOBEC3B expression was not related to the prognosis in ER-negative tumors.

Conclusions: The high APOBEC3B expression was related to the aggressive phenotype of breast cancer and the poor prognosis.

Citation Format: Eriko Tokunaga, Nami Yamashita, Kimihiro Tanaka, Yuka Inoue, Hiroshi Saeki, Eiji Oki, Hiroyuki Kitao, Yoshihiko Maehara. Expression of APOBEC3B in primary breast cancer of Japanese women [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-06-06.