中国普外基础与临床杂志

中国普外基础与临床杂志

PIK3CA 和 TP53 基因突变与乳腺癌分子分型及组织学分级相关性的研究

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目的 分析乳腺癌突变基因与乳腺癌分子分型和组织学分级的关系,为进一步治疗提供参考依据。 方法 回顾性收集 2016 年 2 月至 2017 年 8 月期间广东省东莞市妇幼保健院和东莞厚街医院诊治的 46 例未行化疗的乳腺癌患者的病理切片标本,采用免疫组织化学染色技术检测肿瘤组织的雌激素受体(ER)、孕激素受体(PR)及人表皮生长因子受体-2(HER-2)的表达,并对病理切片组织进行分级。使用多重 PCR 技术,扩增所选择的 50 个肿瘤相关基因的 207 个热点突变区域,然后采取高通量的半导体测序平台(SSP)进行检测。 结果 46 例乳腺癌患者的组织学分级:Ⅰ 级 8 例,Ⅱ 级 18 例,Ⅲ 级 20 例;ER/PR/HER-2 状态分型:Luminal A 型 10 例,Luminal B 型 23 例,HER-2 过表达型 8 例,besal-like 型 5 例。所有样本共检测到 8 种基因的 33 个位点突变,包括 AKT1、APC、BRAF、CDKN2A、KRAS、PTEN、PIK3CA 和 TP53 基因,其中 PIK3CA 基因突变 26 例,TP53 基因突变 19 例,其余突变基因各检出 1 例。乳腺癌的总基因突变情况与组织学分级和分子分型均无关(P>0.05);PIK3CA 基因突变与乳腺癌的组织学分级相关,组织学分级越低 PIK3CA 基因的突变频率越高(P<0.05);TP53 基因突变与 HER-2 的表达有关(P<0.05)。 结论 PIK3CA 基因在组织学分级Ⅰ级患者中的突变率明显增高;TP53 基因突变与 HER-2 表达成正相关。

Objective To provide reference for further treatment by analyzing the relationship between mutant genes of breast cancer and histological classification and molecular typing of breast cancer. Methods Retrospectively collectted the pathological specimens of 46 breast cancer patients who treated by the Dongguan Maternal and Child Health Institute and the Dongguan Houjie Hospital between February 2016 and August 2017 without chemotherapy. Among the selected 46 breast cancer patients, we detect tumor tissue estrogen receptor (ER)/ pregnancy hormone receptor (PR)/human epidermal growth factor receptor-2 (HER-2) status by immunohistochemistry and classify the pathological tissue section. By using multiple PCR techniques, we detected 207 hot mutation regions of the 50 extended tumor-related genes on the semiconductor sequencing platform. Results There were 8 cases of grade Ⅰ, 18 cases of grade Ⅱ, 20 cases of grade Ⅲ in 46 breast cancer patients according to histological grade. Of the 46 cases, there were 23 cases of Luminal B, 10 cases of Luminal A, 8 cases of HER-2, 5 cases of type besal-like according to ER/PR/HER-2 expression status. Moreover, we found that there were 33 gene locus mutations of 8 genes, including AKT1, APC, BRAF, CDKN2A, KRAS, PTEN, PIK3CA, and TP53. Among of them, the mutation of PIK3CA gene took the most of 26 cases, followed by TP53 (19 cases), and one case in the remaining five genes respectively. we found that the gene mutations of breast cancer were not related to the histological classification and molecular type (P>0.05), the PIK3CA gene mutation was related to the histological classification of breast cancer, the lower the histological classification level, the higher PIK3CA gene mutation frequency (P<0.05). TP53 gene mutation was not related to histological grading, but was related to the expression level of HER-2 (P<0.05). Conclusion The combination of PIK3CA gene mutation and histological grading of breast cancer may become a molecular biological indicator to judge the degree of malignancy and prognosis of breast cancer. TP53 gene mutation were positively correlated with HER-2 expression.

关键词: 乳腺癌; 突变谱; 基因筛查; 高通量测序

Key words: breast cancer; mutate spectrum; genetic screening; high-throughput sequencing

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