The frequency of p53, K-ras mutations, and microsatellite instability differs in uterine endometrioid and serous carcinoma -: Evidence of distinct molecular genetic pathways
The frequency of p53, K-ras mutations, and microsatellite instability differs in uterine endometrioid and serous carcinoma -: Evidence of distinct molecular genetic pathways
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DOI：
10.1002/(sici)1097-0142(20000215)88:4
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发表时间：
2000-02-15
期刊：
影响因子：
6.2
通讯作者：
Ellenson, LH
中科院分区：
文献类型：
--
作者：
Lax, SF;Kendall, B;Ellenson, LH
背景两种最常见的子宫内膜癌类型，浆液性（USC）和类浆液性（UEC），在组织病理学表现和生物学行为上有所不同。最近的研究表明，这些差异可能与不同的分子遗传变异。在目前的研究中，作者通过分析一组肿瘤中的所有3种分子遗传学变化，比较了UEC和USC之间K-ras和p53突变以及微卫星不稳定性（MI）的频率。此外，这些分子遗传学改变的分布之间的不同组织病理学分级的UEC确定。作者分析了58例已知MI状态的UEC的K-ras和p53突变。对45例USC和6例USC进行了K-ras和p53基因检测。这些结果与USC. ACS中p53突变（21例）和MI（34例）的既往数据相结合。57例UEC中有16例（28%）存在MI，但34例USC中无MI。通过外显子5-8的直接测序，在42例UEC中的7例（17%）和27例USC中的25例（93%）中发现p53突变。p53突变的UEC和USCs在约85%的病例中表现出强的p53免疫反应性，而约15%的病例为免疫阴性。聚合酶链反应扩增外显子1后进行寡核苷酸斑点杂交，发现58例UEC中有15例（26%）和45例USC中仅有1例（2%）存在K-ras第12位密码子突变。值得注意的是，K-ras和p53突变和MI的频率在UEC和USC之间有显著差异（P < 0.001）。在子宫内膜癌中，MI和K-ras基因突变发生在低级别和高级别肿瘤中，而p53基因突变几乎只发生在高级别肿瘤中。本研究结果提示，UEC和USC的发病机制涉及不同的分子遗传学途径，低级别UEC可进展为高级别UEC。这些发现支持UEC和USC是独立实体的假设，并表明不同的分子遗传学改变可能是其独特的形态学和生物学行为的原因。(C)2000美国癌症协会
BACKGROUND. The two most common types of uterine endometrial carcinoma, endometrioid (UEC) and serous (USC), differ in their histopathologic appearance and biologic behavior. Recent studies suggest that these differences may be associated with distinct molecular genetic alterations.METHODS. In the current study, the authors compared the frequencies of K-ras and p53 mutations and microsatellite instability (MI) between UEC and USC by analyzing all 3 molecular genetic changes in one set of tumors. Furthermore, the distribution of these molecular genetic alterations was determined among UECs of different histopathologic grade. The authors analyzed 58 UECs with known MI status for K-ras and p53 mutations. The K-ras and p53 genes were analyzed in 45 and 6 cases of USC, respectively. These results were combined with previous data on p53 mutations (21 cases) and MI (34 cases) in USC.RESULTS. MI was present in 16 of 57 UECs (28%) but in none of 34 USCs. p53 mutations were found in 7 of 42 UECs (17%) and 25 of 27 USCs (93%) by direct sequencing of exons 5-8. UECs and USCs with p53 mutations showed strong immunoreactivity for p53 in about 85% of the cases, whereas about 15% of the cases were immunonegative. K-ras mutations at codon 12 were found in 15 of 58 UECs (26%) and in only 1 of 45 USC (2%) by dot blot oligohybridization after polymerase chain reaction amplification of exon 1. Notably, the frequency of both K-ras and p53 mutations and MI was significantly different between UEC and USC (P < 0.001). In UECs, MI and K-ras mutations occurred in low grade as well as in high grade tumors, whereas p53 mutations were present almost exclusively in high grade tumors.CONCLUSIONS. The results of this study suggest that different molecular genetic pathways are involved in the pathogenesis of UEC and USC and that low grade UEC may progress to high grade UEC. These findings support the hypothesis that UEC and USC are separate entities and suggest that different molecular genetic alterations may be responsible for their distinct morphology and biologic behavior. (C) 2000 American Cancer Society.