Kanavaros P, Vlychou M, Stefanaki K, Rontogianni D, Gaulard P, Pantelidaki E, Zois M, Darivianaki K, Georgoulias V, Boulland M L, Gorgoulis V, Kittas C
Department of Pathology, University of Crete, Greece.
Anticancer Res. 1999 Mar-Apr;19(2A):1209-16.
Recent studies have shown that some peripheral T-cell lymphomas (PTCL) could be derived from lymphocytes with cytotoxic potential. Therefore, we have investigated by immunohistochemistry 34 cases of PTCL including 2 cases of hepatosplenic gamma delta PTCL and 5 cases of sinonasal NK-cell lymphomas as well as 7 cases of T-lymphoblastic lymphomas (T-LBL) for the expression of the cytotoxic proteins TIA-1 and granzyme B. In addition, 50 cases of Hodgkin's disease (HD) were investigated in order to see if these cytotoxic proteins are expressed by Hodgkin and Reed-Sternberg (HRS) cells. Expression of the TIA-1 is characteristic of cytotoxic cells regardless of their activation status whereas expression of granzymes is highly increased in activated cytotoxic cells. All the five cases of sinonasal NK-cell lymphomas expressed TIA-1 and granzyme B in most tumour cells. The two gamma delta PTCL cases expressed TIA-1 protein in most tumour cells but not granzyme B. Of the 32 other PTCL, 9 cases showed cytotoxic protein expression in tumour cells. These cases comprised 2 pleomorphic medium large cell (PML) (1 nodal and 1 intestinal) and 7 CD30 positive anaplastic large cell lymphomas (ALCL) (5 nodal and 2 cutaneous). Cytotoxic protein expression in our series appeared to be related to the location since 10/18 (55%) extranodal PTCL and NK-NHL and only 6/21 (28%) nodal PTCL expressed TIA-1, and related to histology since, in nodal PTCL, this pattern was observed in most anaplastic (5/6 cases) and in a few pleomorphic (1/9 cases) lymphomas, but not in AILD-type NHL (0/6 cases). The 7 cases of T-LBL did not express cytotoxic proteins in tumour cells. EBV was detected by EBER RNA in situ hybridization (RISH) in tumour cells in all 5 sinonasal NK-NHL and in scattered atypical cells in all 6 cases of AILD. Two of the 50 cases of HD weakly expressed TIA-1 and granzyme B in a proportion of HRS cells. EBV was detected by RISH in 19/50 cases of HD but no correlation was found between EBV status and expression of cytotoxic proteins in HRS cells. However, the finding that granzyme B positive cells were found very rarely in close vicinity of HRS cells suggests that the function of activated cytotoxic cells is locally inhibited by the HRS cells and/or the reactive cells in the vicinity of HRS cells. Taken together our data suggest that: a) sinonasal NK-cell NHL represent tumours of activated cytotoxic NK-cells, b) the hepatosplenic gamma delta PTCL represent tumours of nonactivated cytotoxic gamma delta T-cells, c) a small proportion of other PTCL, mostly anaplastic large cell lymphomas represent tumours of cytotoxic T-cells and d) only very few cases of HD expressing cytotoxic proteins in a proportion of tumour cells, could be derived from activated cytotoxic cells.
最近的研究表明，一些外周T细胞淋巴瘤（PTCL）可能起源于具有细胞毒性潜能的淋巴细胞。因此，我们通过免疫组织化学方法，对34例PTCL进行了研究，其中包括2例肝脾γδ PTCL、5例鼻NK细胞淋巴瘤以及7例T淋巴母细胞淋巴瘤（T-LBL），检测细胞毒性蛋白TIA-1和颗粒酶B的表达。此外，还研究了50例霍奇金病（HD），以观察霍奇金和里德-斯腾伯格（HRS）细胞是否表达这些细胞毒性蛋白。TIA-1的表达是细胞毒性细胞的特征，无论其激活状态如何，而颗粒酶在激活的细胞毒性细胞中的表达则显著增加。所有5例鼻NK细胞淋巴瘤的大多数肿瘤细胞均表达TIA-1和颗粒酶B。2例γδ PTCL的大多数肿瘤细胞表达TIA-1蛋白，但不表达颗粒酶B。在其他32例PTCL中，9例肿瘤细胞显示细胞毒性蛋白表达。这些病例包括2例多形性中大型细胞（PML）（1例淋巴结型和1例肠道型）和7例CD30阳性间变性大细胞淋巴瘤（ALCL）（5例淋巴结型和2例皮肤型）。在我们的系列研究中，细胞毒性蛋白表达似乎与部位有关，因为18例结外PTCL和NK-NHL中有10例（55%）表达TIA-1，而21例淋巴结PTCL中只有6例（28%）表达TIA-1；也与组织学有关，因为在淋巴结PTCL中，这种模式在大多数间变性淋巴瘤（5/6例）和少数多形性淋巴瘤（1/9例）中可见，但在AILD型NHL中未见（0/6例）。7例T-LBL的肿瘤细胞未表达细胞毒性蛋白。通过EBER RNA原位杂交（RISH）在所有5例鼻NK-NHL的肿瘤细胞中以及所有6例AILD的散在非典型细胞中检测到EBV。50例HD中有2例在部分HRS细胞中弱表达TIA-1和颗粒酶B。通过RISH在19/50例HD中检测到EBV，但未发现EBV状态与HRS细胞中细胞毒性蛋白表达之间存在相关性。然而，在HRS细胞附近极少发现颗粒酶B阳性细胞，这一发现提示激活的细胞毒性细胞的功能在局部受到HRS细胞和/或HRS细胞附近反应性细胞的抑制。综合我们的数据表明：a）鼻NK细胞NHL代表激活的细胞毒性NK细胞肿瘤；b）肝脾γδ PTCL代表未激活的细胞毒性γδ T细胞肿瘤；c）一小部分其他PTCL，主要是间变性大细胞淋巴瘤代表细胞毒性T细胞肿瘤；d）只有极少数HD病例在部分肿瘤细胞中表达细胞毒性蛋白，可能起源于激活的细胞毒性细胞。
