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The Impact of Androgen Receptor and Histone Deacetylase 1 Expression on the Prognosis of Ductal Carcinoma In Situ

Journal of Breast Cancer 2020년 23권 6호 p.610 ~ 621
이충만, 정일용, 박양순, 윤경원, 조휘경, 박혜진, 이희진, 이새별, 김희정, 고범석, 이종원, 손병호, 안세현, 김지선,
소속 상세정보
이충만 ( Lee Choong-Man ) - University of Ulsan College of Medicine Asan Medical Center Department of Surgery
정일용 ( Chung Il-Yong ) - University of Ulsan College of Medicine Asan Medical Center Department of Surgery
박양순 ( Park Yang-Soon ) - University of Ulsan College of Medicine Asan Medical Center Department of Pathology
윤경원 ( Yun Keong-Won ) - University of Ulsan College of Medicine Asan Medical Center Department of Surgery
조휘경 ( Jo Hwi-Gyeong ) - Asan Medical Center Department of Biomedical Science
박혜진 ( Park Hye-Jin ) - University of Ulsan College of Medicine Asan Medical Center Department of Surgery
이희진 ( Lee Hee-Jin ) - University of Ulsan College of Medicine Asan Medical Center Department of Pathology
이새별 ( Lee Sae-Byul ) - University of Ulsan College of Medicine Asan Medical Center Department of Surgery
김희정 ( Kim Hee-Jeong ) - University of Ulsan College of Medicine Asan Medical Center Department of Surgery
고범석 ( Ko Beom-Seok ) - University of Ulsan College of Medicine Asan Medical Center Department of Surgery
이종원 ( Lee Jong-Won ) - University of Ulsan College of Medicine Asan Medical Center Department of Surgery
손병호 ( Son Byung-Ho ) - University of Ulsan College of Medicine Asan Medical Center Department of Surgery
안세현 ( Ahn Sei-Hyun ) - University of Ulsan College of Medicine Asan Medical Center Department of Surgery
김지선 ( Kim Ji-Sun ) - University of Ulsan College of Medicine Asan Medical Center Department of Surgery

Abstract


Purpose: Factors associated with invasive recurrence (REC) of ductal carcinoma in situ (DCIS) are less known. This study was aimed at identifying better biomarkers to predict the prognosis of DCIS.

Methods: RNA extracted from formalin-fixed paraffin-embedded blocks of twenty-four pure DCIS cases was subjected to differential gene expression analysis. The DCIS cases were selected by matching age and estrogen receptor status. Sixteen REC-free and 8 invasive-REC cases with disease-free interval of > 5 years were analyzed. Immunohistochemistry (IHC) staining was used to validate sixty-one independent pure DCIS cases, including invasive-REC (n = 16) and REC-free (n = 45) cases.

Results: Eight differentially expressed genes (DEGs) were statistically significant (log 2-fold change [FC] < ?1 or > 1 and p < 0.001). Less than ½ fold expression of CUL1, androgen receptor (AR), RPS27A, CTNNB1, MAP3K1, PRKACA, GNG12, MGMT genes was observed in the REC group compared to the no evidence of disease group. AR and histone deacetylase 1 (HDAC1) genes were selected for external validation (AR: log 2-FC ? 1.35, p < 0.001, and HDAC1: log 2-FC ? 0.774, p < 0.001). External validation showed that the absence of AR and high HDAC1 expression were independent risk factors for invasive REC (hazard ratio [HR], 5.04; 95% confidence interval [CI], 1.24?20.4; p = 0.023 and HR, 3.07; 95% CI, 1.04?9.04; p = 0.042). High nuclear grade 3 was also associated with long-term invasive REC.

Conclusion: Comparative gene expression analysis of pure DCIS revealed 8 DEGs among recurring cases. External validation with IHC suggested that the absence of AR and overexpression of HDAC1 are associated with a greater risk of long-term invasive REC of pure DCIS.

키워드

Receptors, androgen; Carcinoma, intraductal, noninfiltrating; Histone deacetylase 1; Prognosis

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