AIM: To investigate the expression deficiency of key molecular markers in the homologous recombination pathway. METHODS: Expression loss of breast cancer type 1 susceptibility protein (BRCA1), ataxia telangiectasia mu...AIM: To investigate the expression deficiency of key molecular markers in the homologous recombination pathway. METHODS: Expression loss of breast cancer type 1 susceptibility protein (BRCA1), ataxia telangiectasia mutated (ATM), ATM-Rad3-related (ATR), mediator of DNA damage checkpoint protein 1 (MDC1) and meiotic recombination 11 (Mre11) were correlated with their clinicopathological parameters in gastric cancer (GC). One hundred and twenty treatment-naive GC samples were formalin-fixed and paraffin-embedded into tissue blocks. Two representative cores from each block were extracted and constructed into tissue microarrays. Expression levels of BRCA1, ATM, ATR, MDC1 and Mre11 were determined using immunohistochemical analysis, and correlated with clinical parameters, including age, gender, Lauren subtype, tumor grades, clinical stage and overall survival.RESULTS: Expression loss of BRCA1, ATM, ATR, MDC1, and Mre11 was found in 21.4%, 20.2%, 21.0%, 11.1% and 4.6%, respectively, of interpretable cases. BRCA1 loss was significantly associated with patients of diffused subtype (intestinal vs diffused, 8.2% vs 31.7%, P = 0.001), higher tumor grade (Ⅰ/Ⅱ vs Ⅲ, 10.7% vs 20.5;Ⅰ/Ⅱ vs Ⅳ, 10.7% vs 54.5%, P = 0.047) and advanced clinical stage (Ⅰ/Ⅱ vs Ⅲ, 12.9% vs 16.9%;Ⅰ /Ⅱ vs Ⅳ, 12.9% vs 45.5%, P = 0.006). MDC1 loss was significantly associated with patients of diffused subtype (intestinal vs diffused, 0% vs 19.7%, P = 0.001) and higher tumor grade (Ⅰ/Ⅱ vs Ⅲ, 0% vs 12%;Ⅰ/Ⅱ vs Ⅳ, 0% vs 30.8%, P = 0.012). In addition, the survival time of the patients with expression loss of BRCA1 was significantly shorter than those with positive expression of BRCA1 (2-year survival rate, 32.4% vs 62.8%, P = 0.015). No correlations were found between clinicopathological parameters and expression loss of ATM, ATR and Mre11. CONCLUSION: Our results support the hypothesis that homologous recombination deficiency plays an important role in the progression of gastric carcinoma. Loss of expression of BRCA1 and M展开更多
三阴性乳腺癌(triple-negative breast cancer,TNBC)标准新辅助化疗方案是蒽环序贯紫衫,在此基础上联合铂类能显著提高病理学完全缓解率和远期生存率,但同时会带来治疗相关不良反应。如何精准预测获益人群是目前研究的重点。同源重组修...三阴性乳腺癌(triple-negative breast cancer,TNBC)标准新辅助化疗方案是蒽环序贯紫衫,在此基础上联合铂类能显著提高病理学完全缓解率和远期生存率,但同时会带来治疗相关不良反应。如何精准预测获益人群是目前研究的重点。同源重组修复缺陷(homologous recombination deficiency,HRD)能识别从新辅助含铂方案中获益的患者,特别是BRCA野生型但携带HRD的肿瘤。对于BRCA突变患者,以蒽环为基础的新辅助化疗已足够;而非HRD携带者将不能从铂类药物中获益。展开更多
三阴性乳腺癌(triple negative breast cancer,TNBC)是高度异质性与侵袭性的乳腺癌亚型,由于目前缺乏较为明确的治疗靶点,化疗依然是TNBC的主要治疗手段,但病变易复发、转移,临床预后差。近年来,多组学新技术的应用与发现,尤其是蛋白质...三阴性乳腺癌(triple negative breast cancer,TNBC)是高度异质性与侵袭性的乳腺癌亚型,由于目前缺乏较为明确的治疗靶点,化疗依然是TNBC的主要治疗手段,但病变易复发、转移,临床预后差。近年来,多组学新技术的应用与发现,尤其是蛋白质基因组学、单细胞组学等研究及个体化临床试验取得的新进展,为TNBC精准化和个体化诊疗带来新的曙光。该文就当前TNBC分子分型和精准治疗新进展等进行综述。展开更多
文摘AIM: To investigate the expression deficiency of key molecular markers in the homologous recombination pathway. METHODS: Expression loss of breast cancer type 1 susceptibility protein (BRCA1), ataxia telangiectasia mutated (ATM), ATM-Rad3-related (ATR), mediator of DNA damage checkpoint protein 1 (MDC1) and meiotic recombination 11 (Mre11) were correlated with their clinicopathological parameters in gastric cancer (GC). One hundred and twenty treatment-naive GC samples were formalin-fixed and paraffin-embedded into tissue blocks. Two representative cores from each block were extracted and constructed into tissue microarrays. Expression levels of BRCA1, ATM, ATR, MDC1 and Mre11 were determined using immunohistochemical analysis, and correlated with clinical parameters, including age, gender, Lauren subtype, tumor grades, clinical stage and overall survival.RESULTS: Expression loss of BRCA1, ATM, ATR, MDC1, and Mre11 was found in 21.4%, 20.2%, 21.0%, 11.1% and 4.6%, respectively, of interpretable cases. BRCA1 loss was significantly associated with patients of diffused subtype (intestinal vs diffused, 8.2% vs 31.7%, P = 0.001), higher tumor grade (Ⅰ/Ⅱ vs Ⅲ, 10.7% vs 20.5;Ⅰ/Ⅱ vs Ⅳ, 10.7% vs 54.5%, P = 0.047) and advanced clinical stage (Ⅰ/Ⅱ vs Ⅲ, 12.9% vs 16.9%;Ⅰ /Ⅱ vs Ⅳ, 12.9% vs 45.5%, P = 0.006). MDC1 loss was significantly associated with patients of diffused subtype (intestinal vs diffused, 0% vs 19.7%, P = 0.001) and higher tumor grade (Ⅰ/Ⅱ vs Ⅲ, 0% vs 12%;Ⅰ/Ⅱ vs Ⅳ, 0% vs 30.8%, P = 0.012). In addition, the survival time of the patients with expression loss of BRCA1 was significantly shorter than those with positive expression of BRCA1 (2-year survival rate, 32.4% vs 62.8%, P = 0.015). No correlations were found between clinicopathological parameters and expression loss of ATM, ATR and Mre11. CONCLUSION: Our results support the hypothesis that homologous recombination deficiency plays an important role in the progression of gastric carcinoma. Loss of expression of BRCA1 and M
文摘三阴性乳腺癌(triple-negative breast cancer,TNBC)标准新辅助化疗方案是蒽环序贯紫衫,在此基础上联合铂类能显著提高病理学完全缓解率和远期生存率,但同时会带来治疗相关不良反应。如何精准预测获益人群是目前研究的重点。同源重组修复缺陷(homologous recombination deficiency,HRD)能识别从新辅助含铂方案中获益的患者,特别是BRCA野生型但携带HRD的肿瘤。对于BRCA突变患者,以蒽环为基础的新辅助化疗已足够;而非HRD携带者将不能从铂类药物中获益。
文摘三阴性乳腺癌(triple negative breast cancer,TNBC)是高度异质性与侵袭性的乳腺癌亚型,由于目前缺乏较为明确的治疗靶点,化疗依然是TNBC的主要治疗手段,但病变易复发、转移,临床预后差。近年来,多组学新技术的应用与发现,尤其是蛋白质基因组学、单细胞组学等研究及个体化临床试验取得的新进展,为TNBC精准化和个体化诊疗带来新的曙光。该文就当前TNBC分子分型和精准治疗新进展等进行综述。
