Wang Xinhong, Fan Mingwen, Chen Xinming, Wang Shuozhi, Alsharif Mohd Jamal, Wang Li, Liu Lijiang, Deng Hao
Department of Endodontics, School and Hospital of Stomatology of Wuhan University, China.
Oral Oncol. 2006 Aug;42(7):740-4. doi: 10.1016/j.oraloncology.2005.11.018. Epub 2006 Feb 7.
To assess the difference in genetic aberration patterns among the invasive tumor front (ITF), center/superficiality and the stroma adjacent to oral squamous cell carcinoma (OSCC), we studied loss of heterozygosity (LOH) and microsatellite instability (MI) at chromosome 9p21 and 17p13 on the three regions by combining laser capture microdissection (LCM) and PCR. We studied 20 OSCC patients with TP53 on chromosome 17p13 and RPS6 on chromosome 9p21. Genomic DNA samples from the ITF, center/superficial and stromal cells adjacent to the tumor were prepared from cryosections using laser-assistant microdissection, then LOH and MI were determined. Cells at the ITF, center/superficiality and stroma showed a high frequency of LOH and MI on chromosomes 17p13 (TP53) and 9p21 (RPS6). Comparison of the patterns of allelic loss and MI encountered at the ITF, center/superficial and stromal cells revealed no concordance. The frequency of RPS6 and TP53 aberration at the epithelial compartment (both ITF and center, 64.7%, 11/17; 70.6%, 12/17) was statistically higher than the stroma (23.5%, 4/17; 43.8%, 7/16) (p<0.05). Furthermore, for the epithelial compartment, the aberrations proportions of TP53 rose from 60.0% (9/15) to 64.7% (11/17) between the center/superficial part and ITF. Also the rate of RPS6 increased from 29.4% (5/17) to 58.8% (10/17) between the center/superficial parts and ITF. The overall frequency of the two markers was statistically higher at the ITF (20/32) than the center/superficial part (15/34) (p<0.05). The current study revealed that intratumor genetic heterogeneity exists in the different histological areas of OSCCs and some particular tumor cell genotypes have correlation with histological patterns.
为评估口腔鳞状细胞癌（OSCC）侵袭性肿瘤前沿（ITF）、中心/表浅区域及邻近基质之间基因畸变模式的差异，我们通过联合激光捕获显微切割（LCM）和聚合酶链反应（PCR），研究了这三个区域9号染色体短臂21区（9p21）和17号染色体短臂13区（17p13）的杂合性缺失（LOH）和微卫星不稳定性（MI）。我们研究了20例OSCC患者，涉及17号染色体短臂13区的TP53基因和9号染色体短臂21区的RPS6基因。使用激光辅助显微切割技术从冰冻切片中制备来自ITF、肿瘤中心/表浅区域及邻近肿瘤的基质细胞的基因组DNA样本，然后测定LOH和MI。ITF、中心/表浅区域及基质细胞在17号染色体短臂13区（TP53）和9号染色体短臂21区（RPS6）显示出较高频率的LOH和MI。对ITF、中心/表浅区域及基质细胞中观察到的等位基因缺失和MI模式进行比较，未发现一致性。上皮区（ITF和中心，分别为64.7%，11/17；70.6%，12/17）中RPS6和TP53基因畸变频率在统计学上高于基质区（分别为23.5%，4/17；43.8%，7/16）（p<0.05）。此外，对于上皮区，中心/表浅区域与ITF之间，TP53基因畸变比例从60.0%（9/15）升至64.7%（11/17）。同样，中心/表浅区域与ITF之间，RPS6基因畸变率从29.4%（5/17）增至5捌%（10/17）。这两个标志物的总体频率在ITF（20/32）高于中心/表浅区域（15/34）（p<0.05）。当前研究表明，OSCC不同组织学区域存在肿瘤内基因异质性，且某些特定肿瘤细胞基因型与组织学模式相关。
