The clinical outcomes of ductal carcinoma in situ of the breast treated with partial mastectomy without adjuvant radiotherapy
삼중음성 유방암군에서 p53 돌연변이의 유전자 염기서열 분석의 임상적 의의
Dept. of Medicine/석사
Purpose: The p53 gene mutation rate in breast cancer ranges between 20% and 40%. Missense-type mutations have been particularly associated with worse prognosis in breast cancer. The p53 mutation is more frequently present in 56%–82% of triple-negative breast cancer (TNBC) or basal-like breast cancer cases, and only in 13%–22% of luminal subtypes. Previous some studies had showed p53 expression by immunohistochemistry (IHC) in TNBC had influenced poorer prognosis in TNBC, but others reported that p53 expression by IHC had yielded inferior prognostic information than p53 gene sequencing analysis in breast cancer. Hence, we investigated the clinical value of gene sequencing-based analysis of the p53 mutation in Korean TNBC patients.Methods: A total of 476 eligible cases (471 patients), of which 87 were TNBC subtype, who underwent p53 mutation analysis using IHC and polymerase chain reaction-denaturing high performance liquid chromatography (PCR-DHPLC) sequencing between December 2002 and December 2009 were reviewed. The median follow-up period was 47.5 months (1-100 months). Probabilities for relapse-free survival (RFS), disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival (OS) in the TNBC subgroup were estimated using the Kaplan-Meier method, and survival curves for different subgroups were compared by the log-rank test. Multivariate analyses were performed using the Cox proportional hazards model.Results: Sixty-eight (14.3%) of the 476 cases had p53 gene mutations detected by PCR-DHPLC sequencing, and 179 cases (37.6%) showed positive IHC staining of p53. Eighty-seven cases (18.3%) were TNBC, of which 22 (25.3%) showed the p53 gene mutation and 51 (58.6%) had positive IHC staining. In the TNBC subgroup, age was the only clinicopathologic factor showing a significant difference between the p53 wild-type and the p53 mutant subtype. Majority of the p53 mutations were found in exon 7 (31.8%), with missense mutation being the most common type (59.1%). Univariate analysis revealed a significant difference in RFS and DFS in p53 missense-positive and p53 missense-negative TNBC patients, as detected by gene sequencing (p=0.035 and 0.041, respectively). BCSS and OS showed trends towards significance (all p = 0.060). In multivariate analysis, the presence of the p53 missense mutation in TNBC patients was a clinically significant prognostic factor for RFS (p=0.040), BCSS and OS (p=0.048, respectively), and showed a trend for DFS (p=0.050).Conclusion:The p53 missense mutation have a significant clinical prognostic power in predicting RFS, BCSS, and OS in TNBC patients.