鼻咽癌FRA3B脆性部位的杂合性丢失与临床病理特征的关系

Study of relationship between LOH at FRA3B site and clinicopathologic features of nasopharyngeal carcinoma

目的 研究鼻咽癌染色体脆性部位FRA3B区域的等位基因杂合性丢失（loss of heterozygosity，LOH）情况，并探讨LOH与鼻咽癌临床病理特征及EB病毒（Epstein-Barr virus，EBV）感染的关系。方法 选择FRA3B区域的8个微卫星多态标记对40例鼻咽癌组织进行LOH分析。结果 77．5％（31／40）的鼻咽癌在FRA3B脆性部位出现LOH，丢失频率较高的2个位点是D3S1300（55．6％）和D3S2757（50．0％），其共同缺失区为D3S4103-D3S4260。LOH与鼻咽癌的临床病理特征（肿瘤T分期、颈淋巴结转移、临床分期、肿瘤分化程度、肿瘤复发情况及EBV壳抗原IgA抗体滴度）相关，临床Ⅲ～Ⅳ期、低分化鳞癌、肿瘤复发和抗体滴度≥1：40者LOH频率明显高于临床Ⅰ～Ⅱ期、中分化鳞癌、无肿瘤复发及抗体滴度〈1：40者（P〈0．05）。结论 FRA3B脆性部位的LOH为鼻咽癌的频发事件，可能参与了鼻咽癌的发生发展，共同缺失区D3S4103-D3S4260可能是其优先作用的分子靶点。

Objective To define finely the patterns of allelic loss at the FRA3B site in nasopharyngeal carcinoma （NPC） and to detect potential relationship between allelic loss, clinicopathologic features and EpsteinBarr Virus （EBV） infection. Methods Eight high dense polymorphic microsatellite markers within or flanking the FRA3B site were selected to detect the loss of heterozygosity （LOH） in 40 specimens of NPC. Results LOH at the FRA3B site was shown in 31 （77. 5%） primary tumors. The highest frequencies of LOH were found at the two loci： D3S1300 （55. 6%） and D3S2757 （50. 0%）. The common area of deletion was located between D3S4103 and D3S4260. LOH at the FRA3B site was correlated with clinicopathologic features including tumor T-stage, lymph nodal status, clinical stage, tumor differentiation, tumor recurrence and serum IgA antibody titers against EpsteinBarr virus capsid antigen （EBVCA-IgA） in NPC. Frequencies of LOH in NPC of advanced clinical stages （Ⅲ and Ⅳ）, poor differentiation, recurrence and high antibody titers against EBVCA-IgA （≥1 ： 40）, were much higher than those of early clinical （Ⅰ and Ⅱ） stages, moderate differentiation, and low antibody titers against EBVCA-IgA （〈1： 40）. Conclusion Allelic loss at the FRA3B site occurs frequently in NPC. This suggests that the region between D3S4103 and D3S4260 may represent a preferential molecular target in nasopharyngeal carcinogenesis.