摘要
目的分析鼻型NK/T细胞淋巴瘤(N-NK/T-L)组织中c-kit基因突变和表达情况,探讨N-NK/T-L可能的特异分子标记物。方法研究组为36例N-NK/T-L,对照组包括11例同部位B细胞淋巴瘤(BCL)和5例颈部非特殊性外周T细胞淋巴瘤(PTCL);采用免疫组化EnVision法对淋巴瘤进行c-kit产物CD117标记;采用巢式PCR法对31例N-NK/T-L、11例BCL和5例PTCL肿瘤组织c-kit基因11和17号外显子片段进行扩增,PCR纯化产物测序和序列分析。结果N-NK/T-L组织学表现为凝固性坏死,不同大小和异型的肿瘤性淋巴细胞呈破坏性生长浸润于炎性背景中。36例N-NK/T-L免疫组化表达阳性率为:CD45RO75.0%、CD3ε72.2%、TIA183.3%、GranzymeB61.1%、CD5680.5%、CD3030.6%,而全部病例CD117阴性。对照组5例PTCL均为TIA1阳性,仅1例GranzymeB阳性,而11例BCL仅CD20和CD79α阳性,其余标记均阴性。GranzymeB表达与N-NK/T-L肿瘤细胞的异型性具有相关性(P<0.05)。尽管所有病例CD117染色阴性,但c-kit基因11和17外显子扩增序列分析表明8例(8/31,25.8%)N-NK/T-L病例具有基因突变,其中分别有4例涉及11外显子和17外显子;对照组11例BCL和5例PTCL中分别有1例具有11外显子突变。所有突变均为碱基替代错义突变,热点涉及571、572和821位点。结论上述结果提示除组织学特征外,GranzymeB可能是更可靠的N-NK/T-L诊断和鉴别诊断指标。c-kit错义突变可发生于约1/4的N-NK/T-L病例中,该突变可能引起c-kit的功能失调。
Purpose To analyse the c-kit gene mutation and expression in Chinese patients with nasal NK/T-cell lymphoma （ N-NK/T- L）, and explore a potential molecular marker for this disease. Methods 36 cases of N-NK/T-L from 304 cases of malignant lymphomas in North China area were investigated by histopathology, immunophenotyping and genomic analysis of c-kit, in comparison with 11 cases of B-cell lymphoma （BCL） in the same region and 5 cases of nodal peripheral T-cell lymphoma, non-specific （PTCL）. Results Histopathologically, N-NK/T-L was characterized by coagulative necrosis, inflammatory background and angiodestructive growth pat- tern. In 36 cases of N-NK/T-L, 27 cases were positive for CD45RO （75.0%）, 25 for CD3ε （72. 2% ） , 30 （83. 3% ） for T1A1, 22 （61.1%） for granzyme B , 29（80.5% ）for CD56 and 11 （30.6%） for CD30, while none were positive for CDllT. All 5 cases of PTCL displayed positive staining for CD45RO and TIA1, 3 cases for CD3ε, but only one case showed positive for granzyme B. All of the 11 BCL cases presented positive staining for CD20 and CD79α, but negative for other antibodies. Significant relation was observed between neoplastic cells pleomorphism and granzyme B expression（ P 〈 0. 05 ）. Despite all cases were negative for CD117 staining, se- quencing of c-kit 11 and 17 exon showed that 8 of 31 N-NK/T-L cases （8/31, 25.8% ） contained the genomic mutations of c-kit, in- cluding 4 cases in exon 11 and 4 in exon 17. For the control group, only 1 of 11 BCL（9% ）and 1 of 5 PTCL （20%） cases were detected to harbor the mutations in exon 11. All mutations detected in three groups were mis-sense by base-substitution and codes 571,572 and 821 were hot-spot. Conclusions In addition to histological features in N-NK/T-L, granzyme B expression might be a more reliable marker in differential diagnosis, and genomic mis-sense mutation of c-kit could be detected at least in one-fourth of N-NK/T-L.
出处
《临床与实验病理学杂志》
CAS
CSCD
北大核心
2007年第6期645-649,共5页
Chinese Journal of Clinical and Experimental Pathology
基金
国家自然科学基金(30270517)
教育部教育振兴行动计划专项基金(985工程)
