Genomic gain of PIK3CA and increased expression of p110alpha are associated with progression of dysplasia into invasive squamous cell carcinoma
Genomic gain of PIK3CA and increased expression of p110alpha are associated with progression of dysplasia into invasive squamous cell carcinoma
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DOI：
10.1002/path.1207
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发表时间：
2002-11-01
影响因子：
7.3
通讯作者：
Stahl, U
中科院分区：
文献类型：
--
作者：
Woenckhaus, J;Steger, K;Stahl, U
PIK 3CA编码磷脂酰肌醇3-激酶（PI 3 K）的催化亚基p110 α，在恶性疾病中被激活。然而，PIK 3CA基因畸变在头颈部鳞状细胞癌（HNSCC）肿瘤发生中的作用迄今尚不清楚。本研究旨在通过荧光原位杂交（FISH）与YAC探针，含有PIK 3CA基因，从福尔马林固定的组织切片的组织形态学明确定义的区域分离间期核，并比较这些数据与p110 α的蛋白质和mRNA表达，以确定在侵袭性HNSCC和异型增生前体病变的PIK 3CA基因组畸变。通过原位杂交和免疫组化分别对连续组织切片上p110 α的mRNA和蛋白水平进行评估。在6例低度至中度发育不良中的1例（17%）和9例高度发育不良中的7例（78%）以及11例癌（100%）中观察到3q 26的拷贝数增加。此外，7例高度发育不良中的1例（14%）和11例癌中的6例（55%）有3q 26扩增。大多数情况下，拷贝数增益超过50%的细胞和/或扩增超过10%的细胞显示增加p110 α mRNA和蛋白表达，而只有两个案例（18%）（一个高度异型增生和一个癌）没有增益或低水平增益显示增加p110 α蛋白表达。这些数据表明，3q 26拷贝数增加和扩增代表HNSCC癌变过程中的早期基因组畸变。此外，HNSCC中p110 α mRNA和蛋白表达可能受这些基因组畸变以及表观遗传事件的调节。版权所有（C）2002约翰威利父子有限公司
PIK3CA, encoding the catalytic subunit p110alpha of phosphatidylinositol 3-kinase (PI3K), is activated in malignant diseases. However, the role of the PIK3CA gene aberrations for tumourigenesis of head and neck squamous cell carcinoma (HNSCC) is to date unclear. The present study was designed to determine the genomic aberration of PIK3CA in invasive HNSCC and dysplastic precursor lesions by fluorescence in situ hybridization (FISH) with a YAC probe, containing the PIK3CA gene, on isolated interphase nuclei from histomorphologically well-defined regions of formalin-fixed tissue sections and to compare these data with protein and mRNA expression of p110alpha. The mRNA and protein levels of p110alpha were assessed, respectively, by in situ hybridization and immunohistochemistry on consecutive tissue sections. Copy number gains at 3q26 were observed in one of six low-to-moderate dysplasias (17%) and in seven of nine high-grade dysplasias (78%), as well as in 11 carcinomas (100%). In addition, one of seven high-grade dysplasias (14%) and 6 of 11 carcinomas (55%) had amplifications of 3q26. The majority of cases with copy number gain in more than 50% of the cells and/or amplification in more than 10% of cells showed increased p110alpha mRNA and protein expression, whereas only two cases (18%) (one high-grade dysplasia and one carcinoma) with no gain or low-level gain displayed increased p110alpha protein expression. These data suggest that 3q26 copy number gain and amplification represent early genomic aberrations in HNSCC carcinogenesis. In addition, p110alpha mRNA and protein expression in HNSCC may be regulated by these genomic aberrations as well as by epigenetic events. Copyright (C) 2002 John Wiley Sons, Ltd.