The Expression Of PDL1?TGF?1 In LCH Of Children And Its Clinicopathological Analysis

Objective:To study the expression of PD1,PDL1,PDL2,TGF ? 1 and SMAD6 in children with Langerhans cell histiocytosis(LCH)and its correlation with clinical and BRAF V600E mutation.Methods:Forty children with LCH who were diagnosed in our department from January 2012 to September 2018 were selected.the clinical and pathological manifestations were reviewed and compared according to the system involvement.The skin biopsies of 30 children with fresh and intact paraffin specimens were selected for immunohistochemistry of PD1,PDL1,PDL2,TGF ? 1 and SMAD6,and the mutation of BRAF V600E gene was detected by immunohistochemistry.The expression and its relationship with gene mutation,clinical manifestation and prognosis were analyzed.Results:1)In 40 children with LCH,the ratio of male to female was 0.9:1.The average age of onset was 4.60±3.57 months.55.0%(22/40)had fever.Skin involvement was found in all 40 cases,bone damage was found in 35.0%(14/40),and high risk organs were involved in 40%(16/40).Only skin involvement was found in 35%(14/40)and MS-LCH in 65.0%(26/40).33 cases were followed up and 7 cases were lost.4 cases(12.1%)died,8 cases had recurrence or progression in the course of disease,7 cases were still in chemotherapy,14 cases were improved.2)The onset age of LCH with skin involvement was earlier than that of MS-LCH group(p=0.022).3)The positive expression of PD1 was found in 30%(9/30)of LCH.The expression of PDL1 was positive in 60%(18/30)LCH,PD1 and PDL1 were strongly positive in 1 case of congenital self-healing LCH,and the positive rate of TGF?1 expression was 70.4%(19/30).The expression of PDL1 and TGF?1 in 30 cases of LCH was not significantly different from the age of onset,risk group,multi-system involvement,fever and recurrence(p>0.05).No positive expression of PDL2 and SMAD6 was found in 30 cases.4)53.3%(16/30)of BRAF V600E gene mutations were positive by immunohistochemistry.Positive rate of BRAF V600E gene mutation and sex,age of onset,fever,rash type,risk grouping,multiple system involvement,recurrence,expression of PDL1 and TGF?1 and overall survival rate.No significant difference was found(p > 0.05).Conclusions:1)The onset age of LCH children with skin lesions as a single manifestation is younger than that of patients with multi-system involvement,and the manifestation of rash is not related to the clinical classification.2)There were different degrees of expression of PD1,PDL1 and TGF ? 1 in LCH skin lesions of children,but no expression of PDL2 and SMAD6.The expression of PD1,PDL1 and TGF ? 1 was not related to system involvement,risk grouping and prognosis,TGF ? 1 may play a role in the pathogenesis of LCH.3)BRAFV600E mutation was found in 53.3% of children with LCH,and was not related to system involvement,risk grouping and prognosis.