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

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。

Objective 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 CD3ε, CD56, eytotoxic granules and positivity of EBV in 20 cases. The RT-PCR resnhs 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 rnucosa 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, and suggests that the tumor cells of most cases arc 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.