Abstract P6-09-46: A comprehensive analysis of GNAS DNA copy number, levels of mRNA and protein expression in primary breast cancer

Background : Result of recent advances in genetics, guanine nucleotide binding protein, alpha stimulating (GNAS), transducer of signals from G-protein coupled receptors, has been noted that this factor is related with the onset and progression of tumor in various cancers. We aimed to analyze gene amplification, mRNA and protein expression of GNAS and their potential association with clinicopathological factors and prognosis in primary breast cancer. Methods : The cohort of this study included 432 primary invasive breast cancer patients treated with standard care at Kumamoto University Hospital between June 2000 and January 2011. We performed a comprehensive analysis of GNAS at the levels of gene copy number, mRNA and GNAS protein expression analyzed by qPCR, qRT-PCR and immunohistochemistry (IHC), respectively. In the IHC assessment of GNAS protein expression, an H-score ≥ 150 was observed in 241 patients (55.8%) who were defined as having a high protein expression level. Results : The median age at diagnosis was 60 (range 27-93). Three hundred fifteen (72.9%) of these were postmenopausal women. One hundred forty two patients (32.9%) had axillary lymph node metastasis. The median Ki67 labeling index was 23.6 (range 0.5-97.0). The subtypes were 321 ER+/HER2-, 24 ER+/HER2+, 34 ER-/HER2+ and 53 ER-/HER2-. Three hundred twenty one patients (75.9%) were treated with endocrine therapy and 146 patients (34.6%) chemotherapy. Most notably, a low levels of GNAS protein expression was observed in 191(44.2%) patients, and was positivity associated with Ki67 (P=0.028). Furthermore, univariate and multivariate analysis revealed that low GNAS protein expression was significantly related with poor relapse-free survival rate (Log-rank test; P=0.0013, OR:0.40, 05%CI:0.22-0.70) and breast cancer specific survival rate (Log-rank-test; P=0.041, OR:0.43, 95%CI:0.19-0.97). GNAS amplification and mRNA expression were not correlated with prognoses. Conclusion : Contrary to expectations, GNAS expression was positively related with favorable tumor characteristics. Expression levels of GNAS protein may be an independent prognostic factor for primary breast cancer. Citation Format: Tomiguchi M, Yamamoto Y, Yamamoto-Ibusuki M, Goto-Yamaguchi L, Fujiki Y, Sueta A, Takeshita T, Iwase H. A comprehensive analysis of GNAS DNA copy number, levels of mRNA and protein expression in primary breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-46.