Pescarmona E, Pignoloni P, Santangelo C, Naso G, Realacci M, Cela O, Lavinia A M, Martelli M, Russo M A, Baroni C D
II Cattedra di Anatomia ed Istologia Patologica, Dipartimento di Medicina Sperimentale e Patologia, Policlinico Umberto I, Rome, Italy.
J Pathol. 1999 Aug;188(4):400-6. doi: 10.1002/(SICI)1096-9896(199908)188:4<400::AID-PATH379>3.0.CO;2-#.
The expression of p53 and the retinoblastoma gene has been investigated by immunohistochemical and molecular analysis in 45 cases of nodal peripheral T-cell lymphoma with high-grade histology. Most cases (73.3 per cent) were primary nodal lymphomas without any extra-nodal site involvement. Most of them (75.6 per cent) were histologically classified as pleomorphic, small, medium, and large cell type. Immunohistochemistry detected p53 in nine cases (20 per cent). In each of these cases, the polymerase chain reaction (PCR)/heteroduplex analysis did not show the presence of mutations, this finding being consistent with an alteration of the p53 functional pathway, in the presence of a wild-type protein. The retinoblastoma gene product was detected by immunohistochemistry in 35 cases (77.8 per cent) and not detected in ten cases (22.2 per cent). In the latter cases, the reverse transcription (RT)-PCR analysis showed the presence of a specific retinoblastoma gene transcript in six cases and was negative in the remaining four cases. The immunohistochemical and molecular findings seem to be consistent with abnormalities of retinoblastoma gene expression at either the transcriptional or the post-transcriptional level. Since all nine p53-positive cases by immunohistochemical analysis were also retinoblastoma gene product-positive, and all ten retinoblastoma gene product-negative cases were also p53-negative, two different and mutually exclusive pathways of possible pathogenetic significance may be suggested, the former involving abnormalities of the functional pathway of p53 in the absence of mutations and the latter abnormalities of retinoblastoma gene expression at the transcriptional and/or post-transcriptional level. Finally, the clinico-pathological correlations showed that p53 immunohistochemical expression is significantly associated with a poorer response to intensive chemotherapy.
通过免疫组织化学和分子分析，对45例组织学分级为高级别的淋巴结外周T细胞淋巴瘤患者的p53和视网膜母细胞瘤基因表达情况进行了研究。大多数病例（73.3%）为原发性淋巴结淋巴瘤，无任何结外部位受累。其中大多数（75.6%）在组织学上被分类为多形性、小、中、大细胞型。免疫组织化学检测发现9例（20%）存在p53表达。在这些病例中，聚合酶链反应（PCR）/异源双链分析均未显示存在突变，这一发现与野生型蛋白存在时p53功能途径的改变一致。通过免疫组织化学检测到35例（77.8%）存在视网膜母细胞瘤基因产物，10例（22.2%）未检测到。在后者中，逆转录（RT）-PCR分析显示6例存在特异性视网膜母细胞瘤基因转录本，其余4例为阴性。免疫组织化学和分子学结果似乎与视网膜母细胞瘤基因在转录或转录后水平的表达异常一致。由于免疫组织化学分析中所有9例p53阳性病例同时也是视网膜母细胞瘤基因产物阳性，而所有10例视网膜母细胞瘤基因产物阴性病例同时也是p53阴性，因此可能提示两条不同且相互排斥的具有潜在致病意义的途径，前者涉及无突变情况下p53功能途径的异常，后者涉及视网膜母细胞瘤基因在转录和/或转录后水平的表达异常。最后，临床病理相关性分析显示，p53免疫组织化学表达与强化化疗反应较差显著相关。
