Ma Yingyu, Wu Liang, Liu Cuiping, Xu Liqian, Li Dongmei, Li Ji-Cheng
Institute of Cell Biology, Zhejiang University, 310058, Hangzhou, China.
J Cancer Res Clin Oncol. 2009 Mar;135(3):431-7. doi: 10.1007/s00432-008-0471-6. Epub 2008 Sep 11.
This project explored the influence of loss of heterozygosity (LOH) and microsatellite instability (MSI) of locus D8S277 to PINX1 expression of gastric cancer in Chinese people.
LOH and MSI of locus D8S277 in 90 paraffin-embedded gastric carcinoma specimens were detected by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). Envision immunohistochemistry was used to assess the expression of PINX1.
The frequency of LOH was higher in cases with lymph node metastasis than those without (18.57 vs. 0.00%, P < 0.01), and was higher in the specimens that were at TNM stage III + IV than those at stage I + II (21.43 vs. 2.94%, P < 0.01). In terms of the frequency of MSI, it was lower in cases with lymph node metastasis than those without (10.00 vs. 30.00%,P < 0.05). The positive rate of PINX1 protein was higher in samples without lymph node metastasis than those with lymph node metastasis (80.00 vs. 50.00%, P < 0.01); and was higher in the cases at TNM stage I + II than those at stage III + IV; and was lower in the cases between 40 and 60 years old than those above 60 years old (43.75 vs. 65.52%, P < 0.05).
LOH and MSI of PINX1 may play major role in tumor development and regulate it through different pathways. Because LOH plays a major role in negative expression of PINX1, it can be regarded as a sign of gastric cancer development and MSI may affect the prognosis and tumor turnover.
本项目探讨了中国人胃癌中D8S277位点杂合性缺失(LOH)及微卫星不稳定性(MSI)对PINX1表达的影响。
采用聚合酶链反应-单链构象多态性(PCR-SSCP)检测90例石蜡包埋胃癌标本中D8S277位点的LOH和MSI。采用Envision免疫组化法评估PINX1的表达。
有淋巴结转移的病例中LOH频率高于无淋巴结转移者(18.57%对0.00%,P<0.01),TNM III+IV期标本中的LOH频率高于I+II期(21.43%对2.94%,P<0.01)。就MSI频率而言,有淋巴结转移的病例低于无淋巴结转移者(10.00%对30.00%,P<0.05)。无淋巴结转移样本中PINX1蛋白阳性率高于有淋巴结转移者(80.00%对50.00%,P<0.01);TNM I+II期病例高于III+IV期;40至60岁病例低于60岁以上者(43.75%对65.52%,P<0.05)。
PINX1的LOH和MSI可能在肿瘤发生发展中起主要作用,并通过不同途径对其进行调控。由于LOH在PINX1阴性表达中起主要作用,可将其视为胃癌发生发展的一个标志,而MSI可能影响预后和肿瘤周转。