口腔鳞癌浸润前沿、中心和癌间质TP53、RPS6基因变化的研究

The TP53 and RPS6 alterations at the invasive tumor front,center and stroma of oral squamous cell carcinoma

目的检测微卫星位点 TP53、RPS6在口腔鳞癌浸润前沿、中心及癌间质细胞中的基因变化,揭示口腔鳞癌的生物学行为。方法运用激光捕获显微切割分别获取同一肿瘤浸润前沿、中心及癌间质足量的细胞,提取 DNA,PCR-变性 PAGE 电泳检测 TP53和 RPS6位点的基因变化。结果浸润前沿、中心和癌间质中 TP53和 RPS6存在杂合性缺失(loss of heterozygosity,LOH)和微卫星不稳定(microsatellite instability,MI),发生率从23.5%(4/17)到64.7%(11/17),且 LOH 和(或)MI 的模式存在不同。上皮 TP53和 RPS6的 LOH 和 MI 发生率分别为70.6%(12/17)和64.7%(11/17),间质为43.8%(7/16)和23.5%(4/17),癌实质较间质发生率高,差异有统计学意义(P<0.05)。浸润前沿 TP53的 LOH 发生率为64.7%(11/17),中心为60.0%(9/15)。RPS6在浸润前沿的 LOH 和 MI为58.8%(10/17),中心为29.4%(5/17)。两位点总发生率分别为62.5%(20/32)和44.1%(15/34),差异有统计学意义(P<0.05)。结论部分口腔鳞癌样本浸润前沿、中心和肿瘤间质的基因变化不同,癌实质基因变化率与肿瘤分化程度有关。

Objective To assess the difference of genetic alteration patterns among different areas in the same oral squamous cell carcinoma（OSCC）. Methods Studied the loss of heterozy -gosity （LOH） and microsatellite instability （MI） at chromosomal loci TP53 and RPS6 on the invasive tumor front （ITF）, the center/superficial part and stroma cells by combining laser capture microdissection （ LCM ） and PCR technique. Results There existed a high frequency of LOH and MI on chromosomes loci TP53 and RPS6. The frequency of RPS6 and TP53 aberration at the stroma was 23.5% （4/17） and 43.8% （7/16）, respectively. While in epithelial part （both ITF and center）, it reached up to 64.7% （11/17） and 70. 6% （12/17） respectively, and the difference was significant （P 〈 0. 05 ）. The overall frequency of the two markers was statistically higher at the ITF （ 20/32 ） than at the center/superficial part （ 15/34 ） （ P 〈 0. 05）. Conclusions The current study revealed that genetic alterations were different in different areas of the same tumor and there existed a relationship between the hishological grading and genotypes of OSCC.