İnflamatuar dermatit ve erken evre mikozis fungoides ayırıcı tanısında ve mikozis fungoides progresyon spektrumunda mikroRNA ilişkili proteinlerin ifadesinin değerlendirilmesi

DİLEK KOYUNCU YAMAK

İnflamatuar dermatit ve erken evre mikozis fungoides ayırıcı tanısında ve mikozis fungoides progresyon spektrumunda mikroRNA ilişkili proteinlerin ifadesinin değerlendirilmesi

Thesis Type: Expertise In Medicine

Institution Of The Thesis: Ankara University, Tıp Fakültesi, Cerrahi Tıp Bilimleri Bölümü, Turkey

Approval Date: 2020

Thesis Language: Turkish

Student: DİLEK KOYUNCU YAMAK

Supervisor: AYLİN HEPER

Open Archive Collection: AVESIS Open Access Collection

Abstract:

Aim: MF is a CTCL, which progresses generally slowly with patch and plaque lesions, but sometimes progression with tumors and extracutaneous involvement can be seen in some patients and can show systemic spread. In early stages, resemblance to inflammatory dermatitis both clinically and histopathologically creates a diagnostic problem. It is essential to determine biomarkers that can predict patients who may progress to the advanced stage in which demonstrate diminished survival rate and increased mortality. It is also important to find new treatment targets for the advanced stages where concurrent treatment methods are generally insufficient. In our study, it was aimed to investigate the prognostic effect and diagnostic value of the expression of STAT3, Notch1 and FOXP3 which are regulated by miRNAs, in MF progression and in differential diagnosis of inflammatory dermatitis and early-stage MF. Material-method: A total of 100 patients (20 inflammatory dermatitis, 40 patch stage MF, 20 plaque stage MF and 20 tumor stage MF) which were examined between 2006 and 2019 at Ankara University, School of Medicine, Department of Medical Pathology were included in the study. p-STAT3, Notch1 and FOXP3 antibodies were applied to all cases by immunohistochemical methods and evaluations were performed on digital images. The results for p <0.05 were considered to be statistically significant. Results: In MF cases, pSTAT3 and Notch1 expression increased significantly from patch stage to tumor stage; their expression was higher especially in tumor stage according to patch stage and in tumor MF group according to early MF group where the patch and plaque groups were combined. In MF cases, a statistically insignificant decrease in expression of FOXP3 in atypical lymphocytes from patch stage to tumor stage was observed. However early MF group showed statistically significant increase in FOXP3 expression of dermal lymphocytes according to tumor MF group. There was no difference in terms of p-STAT3, Notch1 and FOXP3 expressions in "inflammatory dermatitis" and "patch MF" groups. In addition, in the "MF with large cell transformation" group, p-STAT3 and Notch1 expressions were higher and the FOXP3 expression of dermal atypical cells and lymphocytes was lower than the "MF without large cell transformation" group. Conclusion: In this study, the detected increase of p-STAT3 expression which is parallel with histological and clinical stage progression and its relation with LCT supports that STAT3 plays a role in MF development and it may be associated with aggressive course and may be an alternative target for treatment. The expression of FOXP3 in the atypical cells supports the presence of Treg phenotype in these cells, but the decreased expression in patients with LCT suggests that this phenotype may not be associated with an aggressive course. Although the reduction of Treg cell number in conjunction with histological stage and clinical stage suggests that it may have a prognostic significance but the immunohistochemical use of FOXP3 as a prognostic marker was not found reliable. It was found that immunohistochemical expression status of STAT3, Notch1 and FOXP3 is not contributed to the differential diagnosis of inflammatory dermatitis and patch stage MF.