Overexpression of p53 protein in cutaneous T cell lymphoma: Relationship to large cell transformation and disease progression
Overexpression of p53 protein in cutaneous T cell lymphoma: Relationship to large cell transformation and disease progression
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DOI：
10.1046/j.1523-1747.1998.00167.x
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发表时间：
1998-05-01
影响因子：
6.5
通讯作者：
Salhany, KE
中科院分区：
文献类型：
--
作者：
Li, GQ;Chooback, L;Salhany, KE
晚期皮肤T细胞淋巴瘤(CTCL)(霉菌样肉芽肿/Sezary综合征)经历大细胞转化(LCT)并发展为大细胞淋巴瘤的分子机制尚不清楚。我们采用免疫组织化学分析和聚合酶链式反应/单链构象多态分析来检测P53基因突变是否与CTCL的疾病进展和LCT有关。对27例CTCL患者37例石蜡包埋活检组织进行P53蛋白免疫组织化学染色，其中15例LCT阳性。37例CTCL组织中有11例P53蛋白过度表达，其中10例(67%)LCT组织中P53蛋白阳性表达主要见于较大的转化细胞。相反，在22例未经肝细胞癌活检组织中，只有一例发现P53免疫染色(p<；0.0004)。连续活检发现2例患者在I；CT后获得了P53的表达，在这两例患者中，最初的诊断活检没有LCT，免疫染色显示P53阴性。所有P53蛋白阳性的活检组织均来自晚期皮损(皮肤肿瘤或皮肤外部位)，12例斑块/斑块期CTCL活检组织均未见P53染色。应用聚合酶链式反应/单链构象多态分析方法对11例有冰冻组织可用的P53外显子4~8进行序列分析。6例P53蛋白表达阳性的病例均未检测到突变。这些结果表明，在大多数情况下，LCT中P53蛋白的过度表达和CTCL的疾病进展是通过P53基因突变以外的机制进行的。
The molecular mechanisms by which advanced cases of cutaneous T cell lymphoma (CTCL) (mycosis fungoides/Sezary syndrome) undergo large cell transformation (LCT) and develop the morphologic appearance of a large cell lymphoma, are undefined. We used immunohistochemical analysis and polymerase chain reaction/single strand conformational polymorphism to examine whether p53 mutations are associated with disease progression and LCT in CTCL. p53 protein immunohistochemistry was performed on 37 paraffin embedded biopsies from 27 patients with CTCL; LCT was present in 15 biopsies. Overexpression of p53 protein was found in 11 of 37 CTCL biopsies including 10 of 15 biopsies (67%) with LCT in which p53 staining was predominantly seen in large transformed cells. In contrast, p53 immunostaining was found in only one of 22 CTCL biopsies without LCT (p < 0.0004). Serial biopsies revealed acquisition of p53 expression following I;CT in two patients in whom initial diagnostic biopsies without LCT were p53 negative by immunostaining. All p53 protein positive biopsies were from advanced lesions (cutaneous tumors or extracutaneous sites); none of 12 patch/plaque stage CTCL biopsies demonstrated p53 staining. Polymerase chain reaction/single strand conformational polymorphism and sequencing analysis of p53 exons 4-8 was performed in 11 cases where frozen tissue was available. No mutations were detected in six cases positive for p53 protein expression. These results suggest overexpression of p53 protein in LCT and disease progression of CTCL by a mechanism other than p53 gene mutation, in most cases.