Reduced ten-eleven translocation and isocitrate dehydrogenase expression in inflammatory hidradenitis suppurativa lesions.

BACKGROUND: As environmental factors appear to predispose patients to hidradenitis suppurativa (HS), studying epigenetic modifications is of interest to further understand the pathogenesis of HS. OBJECTIVES: To study the expression of DNA hydroxymethylation regulators, namely the ten-eleven translocation (TET) and isocitrate dehydrogenase (IDH) family, in the skin of HS patients. MATERIALS & METHODS: Twenty patients with HS and 12 healthy subjects were recruited. We analysed the expression of TET1, TET2, TET3, IDH1, IDH2, IDH3a, and IDH3b in lesional and perilesional HS tissue as well as tissue from healthy controls by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). In addition, immunohistochemistry was performed for TET1, TET2, and TET3. RESULTS: RT-PCR analysis showed that mRNA of all the studied genes was significantly under-expressed in lesional HS skin compared to healthy skin. IDH1 and IDH2 mRNA expression was also significantly lower in perilesional HS skin compared to healthy skin, and TET3 mRNA expression was significantly lower in lesional HS skin compared to perilesional HS skin. RT-PCR analysis for TET1, TET2, and TET3 mRNA expression was confirmed by immunohistochemical analysis. Correlation analysis revealed a significant positive correlation between TET and IDH gene expression in perilesional and lesional HS skin. CONCLUSIONS: Our results suggest that epigenetic changes occur in HS tissue and that aberrant expression of the DNA hydroxymethylation regulators may play a role in the pathogenesis of HS. As epigenetic modifications are reversible, further research into the cause of these aberrant expression patterns is warranted in order to develop possible novel therapeutic approaches.

Expression of PD-L1 in keratoacanthoma and different stages of progression in cutaneous squamous cell carcinoma.

BACKGROUND: Programmed cell death 1 (PD-1) and its ligands (PD-L1) play a major role in the immune responses of a variety of cancers. OBJECTIVES: To investigate the expression of PD-L1 in different progression forms of cutaneous squamous cell carcinoma (cSCC) and keratoacanthoma (KA). METHODS: We performed immunohistochemical staining of 21 KA, 26 actinic keratoses (AK), 20 Bowen´s diseases (BD), and 26 high-risk cSCC. The staining patterns were assessed using the tumour proportion score and staining intensity evaluation. Immunohistology scores were statistically analysed. RESULTS: PD-L1 expression of tumour cells as well as tumour-infiltrating cells (TILs) was significantly higher in KA and cSCC when compared to AK and BD (P = 0.00028 and P = 0.00033, respectively). We observed a very strong positive correlation between the PD-L1 protein expression of tumour cells of KA and the PD-L1 protein expression of TILs (r = 0.97; P < 0.0001). A similar correlation was also found for cSCC (r = 0.86; P < 0.0001). The percentage of PD-L1 + tumours was 33.3% for KA and 26.9% for cSCC. Similarly, the percentage of PD-L1 + TILs in KA and cSCC was 33.3 and 34.6%, respectively. CONCLUSIONS: PD-L1 is differently expressed in cSCC and closely related non-melanoma skin cancer. cSCC exhibit PD-L1 expression in a fourth of cases, indicating that PD1/PD-L1 inhibitors might be beneficial in a proportion of patients with an inoperable or metastatic cSCC. Unlike AK and BD, TILs and tumour cells of KA and cSCC present very similar PD-L1 expression profiles indicating a common immune escape mechanism.