Liu Ting, Willmore-Payne Carlynn, Wallander Michelle L, Layfield Lester J
Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
Appl Immunohistochem Mol Morphol. 2011 Jul;19(4):341-6. doi: 10.1097/PAI.0b013e318201dae8.
Endometrial adenocarcinomas are associated with a variety of molecular abnormalities including microsatellite instability, Kirsten rat sarcoma viral oncogene homolog mutations, and phosphatase and tensin homolog inactivation. Recently, mutations in fibroblast growth factor receptor 2 (FGFR2) have been described but their frequency and clinicopathologic characteristics are incompletely known.
To determine the frequency of mutations in FGFR2 exons 7 and 12, 43 adenocarcinomas of the endometrium were studied by high-resolution melting analysis utilizing unlabeled probes and sequencing.
Three of 43 (7%) endometrial carcinomas harbored FGFR2 exon 7 mutations. All 3 mutations were S252W and occurred in endometrioid (type I) adenocarcinomas. Direct sequencing indicated that 2 of the S252W mutations were heterozygous, whereas 1 was presumably homozygous. No FGFR2 mutations were detected in exon 12.
FGFR2 mutations occur in approximately 7% of adenocarcinomas of the endometrium. Only carcinomas of an endometrioid morphology contain FGFR2 mutations, and in our series all were S252W. FGFR2 exons 7 and 12 unlabeled DNA probes allow for easy screening of endometrial carcinoma for the 2 most common FGFR2 mutations (S252W and N550K). Identification of these mutations may have important implications in directed molecular therapy.
子宫内膜腺癌与多种分子异常有关，包括微卫星不稳定性、 Kirsten 大鼠肉瘤病毒癌基因同源物突变以及磷酸酶和张力蛋白同源物失活。最近，已报道成纤维细胞生长因子受体 2（FGFR2）突变，但其频率和临床病理特征尚不完全清楚。
为了确定 FGFR2 外显子 7 和 12 中的突变频率，利用未标记探针和测序的高分辨率熔解分析研究了 43 例子宫内膜腺癌。
43 例子宫内膜癌中有 3 例（7%）存在 FGFR2 外显子 7 突变。所有 3 个突变均为 S252W，且发生在子宫内膜样（I 型）腺癌中。直接测序表明，2 个 S252W 突变是杂合的，而 1 个可能是纯合的。外显子 12 未检测到 FGFR2 突变。
FGFR2 突变约发生在 7%的子宫内膜腺癌中。只有子宫内膜样形态的癌含有 FGFR2 突变，在我们的系列研究中均为 S252W。FGFR2 外显子 7 和 12 的未标记 DNA 探针可轻松筛查子宫内膜癌中 2 种最常见的 FGFR2 突变（S252W 和 N550K）。识别这些突变可能对定向分子治疗具有重要意义。
