Olisova O Yu, Grekova E V, Varshavsky V A, Gorenkova L G, Alekseeva E A, Zaletaev D V, Sydikov A A
V.A. Rakhmanov Department of Skin and Venereal Diseases, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia, Moscow, Russia.
Acad. A.I. Strukov Department of Pathological Anatomy, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia, Moscow, Russia.
Arkh Patol. 2019;81(1):9-17. doi: 10.17116/patol2019810119.
Mycosis fungoides (MF) is the most common primary cutaneous epidermotropic T-cell lymphoma (80%). The accurate diagnosis of MF confirmed only by clinical, histological and immunohistochemical signs amounts to 50-75%.
To investigate genetic markers (FOXP3, STAT4, IL-12B) for the early diagnosis of MF, to estimate the informative value of used diagnostic techniques (histology, immunophenotyping), and to determine clonality by the T-cell receptor γ-chain genes.
Fifty patients with MF and plaque parapsoriasis (PP) who had been treated at the V.A. Rakhmanov Clinic of Skin and Venereal Diseases and at the National Medical Research Center for Hematology were followed up. A MF group consisted of 27 patients; a PP group included 23 patients, and a control group comprised 10 healthy individuals. The expression of the FOXP3, STAT4, and IL-12B genes was analyzed by TaqMan real time-PCR. The objectives of the study were affected skin portions from patients with MF or PP and healthy individuals.
The investigation revealed a increase in the expression level of STAT4 mRNA transcripts by 9 times in patients with MF compared with those with PP and by 553 times in healthy individuals. There was also a statistically significant predominance of the expression level of STAT4 mRNA transcripts in patients with spotted and plaque stages of MF (180; 318) compared with those with PP and healthy individuals, as well as a sharp decrease in those with erythrodermic MF, which was statistically significant.
MF cannot be diagnosed without comprehensively assessing the clinical, anamnestic, histological, immunophenotypic, and molecular genetic data. The expression level of STAT4 mRNA transcripts is of great importance for the early diagnosis of MF. Inclusion of the level of STAT4 expression in the list of diagnostic signs increases the accuracy of differential diagnosis of MF and PP from 59.1 to 81.8%, respectively.
蕈样肉芽肿（MF）是最常见的原发性皮肤亲表皮性T细胞淋巴瘤（占80%）。仅通过临床、组织学和免疫组化特征准确诊断MF的比例为50 - 75%。
研究用于MF早期诊断的基因标志物（FOXP3、STAT4、IL - 12B），评估所用诊断技术（组织学、免疫表型分析）的信息价值，并通过T细胞受体γ链基因确定克隆性。
对在V.A. 拉赫马诺夫皮肤性病诊所和国家血液学医学研究中心接受治疗的50例MF和斑块状副银屑病（PP）患者进行随访。MF组由27例患者组成；PP组包括23例患者，对照组由10名健康个体组成。通过TaqMan实时荧光定量PCR分析FOXP3、STAT4和IL - 12B基因的表达。研究对象为MF或PP患者以及健康个体的病变皮肤部位。
研究发现，与PP患者相比，MF患者中STAT4 mRNA转录本的表达水平升高了9倍，与健康个体相比升高了553倍。MF斑片期和斑块期患者（分别为180；318）中STAT4 mRNA转录本的表达水平与PP患者和健康个体相比也具有统计学意义上的显著优势，而红皮病型MF患者的该水平则急剧下降，具有统计学意义。
若不综合评估临床、既往史、组织学、免疫表型和分子遗传学数据，无法诊断MF。STAT4 mRNA转录本的表达水平对MF的早期诊断具有重要意义。将STAT4表达水平纳入诊断体征列表可使MF与PP的鉴别诊断准确率分别从59.1%提高到81.8%。
