KRAS Gene Mutation in Colorectal Cancer Is Correlated With Increased Proliferation and Spontaneous Apoptosis

KRAS Gene Mutation in Colorectal Cancer Is Correlated With Increased Proliferation and Spontaneous Apoptosis
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DOI:
10.1309/ajcp7fo2vaxivstp
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发表时间:
2011-02-01
影响因子:
3.5
通讯作者:
Hunt, Jennifer L.
Hunt, Jennifer L.
中科院分区:
医学4区
文献类型:
--
作者:
Liu, Xiuli;Jakubowski, Maureen;Hunt, Jennifer L.

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KRAS突变发生在30%至50%的结直肠癌(CRC)中,并已被认为与增殖和细胞凋亡减少有关。在这项研究中,我们分析了198例CRCs中的KRAS,并比较了KRAS突变和野生型CRCs之间的临床病理变量。此外,来自该队列的90和66个CRC的子集进行了微卫星不稳定性测试和组织形态学评价,并比较了KRAS突变和野生型CRC之间的微卫星不稳定性高(MSI-H)和组织形态学变量的频率。临床病理特征(年龄、性别、肿瘤部位、深度、大小、分级和转移)在KRAS突变型和野生型CRC之间没有差异。与野生型KRAS CRCs相比,KRAS突变CRCs的MSI-H频率较低(15%对42%; P = 0.015),有丝分裂活跃的机会更高(77%vs43%,P = 0.022)和凋亡(77%vs28%,P = 0.00012),核分裂像(P = 0.0002)和凋亡细胞(P = 0.0008)的平均值更高。KRAS突变与更高的肿瘤细胞更新相关。
KRAS mutation occurs in 30% to 50% of colorectal cancers (CRCs) and has been suggested to be associated with proliferation and decreased apoptosis. In this study, we analyzed KRAS in 198 CRCs and compared the clinicopathologic variables between KRAS-mutated and wild-type CRCs. Also, a subset of 90 and 66 CRCs from this cohort underwent microsatellite instability testing and histomorphologic evaluation, and the frequency of microsatellite instability-high (MSI-H) and histomorphologic variables were compared between KRAS-mutated and wild-type CRCs. Clinicopathologic features (age, sex, and tumor site, depth, size, grade, and metastasis) were not different between KRAS-mutated and wild-type CRCs. Compared with wild-type KRAS CRCs, KRAS-mutated CRCs had a lower frequency of MSI-H (15% vs 42%; P = .015), a higher chance of having brisk mitosis (77% vs 43%, P = .022) and apoptosis (77% vs 28%; P = .00012), and a greater mean of mitotic figures (P = .0002) and apoptotic cells (P = .0008). KRAS mutation was associated with higher tumor cell turnover.