PIK3CA基因突变与乳腺癌恶性程度和预后的关系

PIK3CA mutation is an independent indicator of malignant phenotype and prognosis in breast cancer

目的研究PIK3CA基因突变与乳腺癌患者预后的相关性。方法采用聚合酶链反应（PCR）和荧光．单链构像多态性分析法（F—SSCP）检测250例乳腺癌组织中PIK3CA基因7、9、20号外显子突变情况，及其与患者临床病理特征和预后进行的关系。结果250例乳腺癌组织中，PIK3CA基因突变者88例（35．2％），其中7号外显子突变8例（3．2％），9号外显子突变者40例（16．O％），20号外显子突变者47例（18．8％）。PIK3CA基因突变率与患者年龄、淋巴结转移、肿瘤分型、分化程度、染色体倍数性、人表皮生长因子受体2（HER-2）表达及TP53突变无明显相关性（P〉0．05），与肿瘤大小、雌激素受体（ER）和孕激素受体（PR）表达有相关性（P〈0．05）。PIK3CA基因突变的乳腺癌患者生存时间显著降低（P=0．004），尤其是ER阳性和HER-2阴性的患者（均P=0．002）。结论PIK3CA基因突变可能在乳腺癌的发生、发展中起重要作用，而且与肿瘤大小、ER表达情况及生存率有关，可作为判断乳腺癌恶性程度及预后的一个独立的分子生物学指标。

Objective The phosphatidylinositol-3-kinase （PI3K）-AKT signaling pathway is considered to play an important role in tumorigenesis. Frequent somatic mutations in the PI3K subunit p110a （PIK3CA） occur in a variety of cancer types. The purpose of this study was to determine the relationship between PIK3CA mutation in breast cancer and pathological features and outcome of patients. Methods The PIK3CA mutations in exons 7, 9, 20 were screened in 250 primary breast cancers using PCR and fluorescent （F） -SSCP, and the results were analyzed according to their cliniopathological data. Results The frequency of PIK3CA mutations among the 250 cases was 35.2% （88/250） , point mutations in exon 7 were found in 8 （3.2%） eases,40 （16.0%） cases in exon 9 and 47 （18.8%） cases in exon 20. No significant correlation between PIK3CA mutation and age, histological type, differentiation, and lymph node metastasis was observed. Mutations were associated with larger tumor size （P = 0. 004） and positive estrogen receptor status （ P = 0. 008 ）. Patients with PIK3CA mutations showed a significantly worse survival （ P = 0. 004 ）, particularly in those with positive estrogen receptor expression or non-amplified HER-2 （ both P = 0. 002 ）. Conclusions PIK3CA mutations may play an important role in the carcinogenesis and development of breast cancer. The association with large tumor size, ER ＋ and poor survival indicates that PIK3CA mutation could be an independent factor for tumor malignant phenotype and prognosis.