C型凝集素样自然杀伤(NK)细胞受体在结外鼻型NK/T细胞淋巴瘤中表达及意义
Study on expression of natural killer (NK) cell C-type lectin-like receptors in nasal NK/T-cell lymphomas
摘要目的 探讨C型凝集素样自然杀伤(NK)细胞受体CD94和NKG2在结外鼻型NK/T细胞淋巴瘤中的表达及意义.方法 运用逆转录聚合酶链反应(RT-PCR)检测C型凝集素样NK细胞受体CD94和NKG2在经组织形态、免疫组织化学、EB病毒原位杂交及T细胞受体PCR克隆性重排分析确诊的21例结外鼻型NK/T细胞淋巴瘤以及对照组同部位B细胞淋巴瘤8例、淋巴结外周T细胞淋巴瘤(PTCL)10例、脾脏5例、胸腺5例和慢性炎性鼻黏膜5例组织中的表达情况并进行随访.结果 21例结外鼻型NK/T细胞淋巴瘤具有典型的形态学改变,表达CD3ε、CD56和细胞毒蛋白,TCR重排阴性,20例EB病毒阳性;RT-PCR扩增结果显示,在21例结外鼻型NK/T细胞淋巴瘤中,18例(85.7%)CD94呈阳性表达;NKG2总阳性率为95.2%(20/21),各亚基表达阳性率依次为NKG2A/2B(85.7%)、NKG2D(61.9%)、NKG2F(14.3%)、NKG2C,/2E(4.8%).对照组中PTCL和B细胞淋巴瘤均不表达CD94和NKG2,仅2例脾脏和2例慢性炎性鼻黏膜组织表达CD94,1例脾脏组织表达NKG2A/2B,1例胸腺组织表达NKG2D.CD94和NKG2在结外鼻型NK/T细胞淋巴瘤中的表达与T细胞淋巴瘤和B细胞淋巴瘤比较,差异均有统计学意义(P均<0.01).CD94和NKG2同时表达于17例结外鼻型NK/T细胞淋巴瘤,共表达率为81.0%(17/21).结论 CD94和NKG2在结外鼻型NK/T细胞淋巴瘤中呈特异性和顺序性表达,提示多数病例肿瘤细胞处于活化和功能NK细胞阶段.对这些分子的检测有可能成为NK细胞源性淋巴瘤诊断的重要手段.
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abstractsObjective To investigate the expression and possible role of C-type lectin-like natural killer cell receptors, including CD94 and NKG2s, in extranodal NK/T-cell lymphoma, nasal type (EN-NK/ T-NT). Methods Reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect the expression of CD94 and NKG2s in tissue sections of 21 cases of EN-NK/T-NT (confirmed by histology, immunohistochemistry, in-situ hybridization for Epstein-Barr virus ( EBV ) and PCR for T-cell receptor genes) , eight midline B cell lymphomas ( BCL) , 10 peripheral T cell lymphoma of lymph nodes ( PTCL) , five spleens, five thymuses and five chronic nasopharyngitis. Results All 21 cases of EN-NK/T-NT showed typical histological features,with expression of CD38,CD56, cytotoxic granules and positivity of EBV in 20 cases. The RT-PCR results showed a high level expression of CD94 (85. 7% ) and NKG2 members (95. 2% totally, with NKG2A/2B in 85.7%, NKG2D in 61.9%, NKG2F in 14.3%, NKG2C/2E in 4.8%, respectively and sequentially) in EN-NK/T-NT. But in the controls, none of the receptors were detected in TCL(0% ) and BCL(0%), while only a few cases of lymphoid tissues expressed one or two of these receptors (two spleens and two chronic nasopharyngitis mucosa for CD94, one spleen for NKG2A/2B and one thymus for NKG2D). The differences of CD94 and NKG2 expression between EN-NK/T-NT and BCL or TCL were statistically significant (P <0. 01). Co-expression of CD94 and NKG2 was found in 17 out of 21 EN-NK/T-NT cases (81. 0% ). Conclusions The specific and sequential expression nature of CD94 and NKG2 in EN-NK/T-NT, mimicks the developmental expression model in their normal counterparts, andsuggests that the tumor cells of most cases are being activated and keeping in a stage as the functional NK cells. Detection of these molecules may provide a useful tool to confirm the diagnosis of NK cell lymphoma.
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