PIKK3CA and PTEN mutations in uterine endometrioid carcinoma and complex atypical hyperplasia
PIKK3CA and PTEN mutations in uterine endometrioid carcinoma and complex atypical hyperplasia
复制标题
DOI：
10.1158/1078-0432.ccr-06-1375
复制
发表时间：
2006-10-15
影响因子：
11.5
通讯作者：
Ellenson, Lora Hedrick
中科院分区：
文献类型：
--
作者：
Hayes, Monica Prasad;Wang, Hong;Ellenson, Lora Hedrick
目的：子宫内膜样癌（UEC）中抑癌基因PTEN和癌基因PIK3CA突变频繁。PTEN突变也常见于复杂型非典型增生（CAH），UEC的前驱病变。PIK3CA的状态尚未在CAH中探索。在这项研究中，我们评估了CAH和UEC的PTEN和PIK3CA突变。实验设计：肿瘤组织显微解剖，并从29例CAH中提取DNA。DNA可从44例UEC病例中获得，这些病例先前以PTEN突变为特征。对所有73例患者进行PIK3CA基因外显子9和20的直接DNA测序。此外，分析CAH病例的PTEN突变。结果：29例CAH中有2例（7%）和44例UEC中有17例（39%）含有PIK3CA突变（P = 0.003）。29例CAH病例中有14例（48%）有PTEN突变，但无一例同时含有PTEN和PIK3CA突变。44例UEC病例中有25例（57%）有PTEN突变，这25例病例中有12例（48%）还含有PIK3CA突变。结论：PIK3CA是UEC中最常见的癌基因突变，而PTEN突变在CAH中并不常见。因此，与PTEN突变不同，PIK3CA突变与侵袭相关。这些发现表明PIK3CA突变可能作为具有潜在临床用途的侵袭标志物。此外，PIK3CA和PTEN突变可能在子宫内膜肿瘤发生中发挥不同的作用。
Purpose: The tumor suppressor PTEN gene and the PIK3CA oncogene are frequently mutated in uterine endometrioid carcinoma (UEC). PTEN mutations are also common in complex atypical hyperplasia (CAH), the precursor lesion of UEC. The status of PIK3CA has not yet been explored in CAH. In this study, we evaluated both CAH and UEC for PTEN and PIK3CA mutations.Experimental Design: Neoplastic tissue was microdissected, and DNA was extracted from 29 cases of CAH. DNA was available from 44 UEC cases previously characterized for PTEN mutations. Direct DNA sequencing of exons 9 and 20 of the PIK3CA gene was done on all 73 cases. In addition, CAH cases were analyzed for PTEN mutations. Statistical analyses were done using the Fisher's exact test.Results: Two (7%) of 29 CAH and 17 (39%) of 44 UEC cases contained a PIK3CA mutation (P = 0.003). Fourteen (48%) of 29 CAH cases had a PTEN mutation, but none contained both a PTEN and PIK3CA mutation. Twenty-five (57%) of 44 UEC cases had a PTEN mutation, and 12 (48%) of these 25 cases also contained a PIK3CA mutation. Coexistent PIK3CA and PTEN mutations were significantly correlated with UEC compared with CAH (P = 0.002), but the association in UEC did not reach statistical significance (P = 0.21).Conclusions: PIK3CA is the most commonly mutated oncogene in UEC; however, mutations are uncommon in CAH. Thus, mutations in PIK3CA, unlike PTEN mutations, are associated with invasion. These findings suggest that mutations in PIK3CA may serve as a marker of invasion with potential clinical use. Furthermore, PIK3CA and PTEN mutations may play distinct roles in endometrial tumorigenesis.