Αρχειοθήκη ιστολογίου

Αλέξανδρος Γ. Σφακιανάκης
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5
Άγιος Νικόλαος Κρήτη 72100
2841026182
6032607174

Κυριακή 25 Φεβρουαρίου 2018

Altered epigenetic pathways and cell cycle dysregulation in healthy appearing skin of patients with koebnerized squamous cell carcinomas following skin surgery

Abstract

Background

Koebnerized non-melanoma skin cancer following skin trauma represents a rare and obscure event.

Objectives

To study molecularpathological parameters in koebnerized squamous cell carcinomas (K-SCCs) occurring after complete tumour removal.

Methods

We assessed two patients with multiple sclerosis who were on treatment with dimethylfumarate (DMF) preceded by long-term azathioprine therapy. Both patients rapidly developed several K-SCCs following histopathologically proven complete excision of cutaneous SCCs. We performed immunohistochemistry for p53, p16, Ki-67, TET-2, IDH-2, 5-hmc, and 5-mc. PCR was carried out for the detection of human papilloma viruses. Mutation analysis was performed for BRAF, K-RAS, and EGFR.

Results

All lesions investigated were negative for HPV DNA. Mutations were not detected. Healthy appearing skin of both patients showed relatively high Ki-67, p16, and p53 expression which was comparable to the expression observed in primary SCCs as well as K-SCCs. Protein expression of Ki-67, p16, and mutant p53 was barely detected in the specimens of the healthy controls. A decreased protein expression of TET-2 enzyme was seen in all tumours and healthy appearing skin when compared to the skin of healthy controls.

Conclusions

We observed two patients with K-SCCs developing under DMF treatment. In healthy appearing skin of patients with K-SCCs, wound healing processes, including induction of proliferation and growth factor release, might promote the growth of pre-neoplastic keratinocytes and cancer formation on the basis of pre-existing altered epigenetic pathways and cell cycle dysregulation. Although fumarates can reduce TET-2 expression, the role of DMF intake in the development of K-SCCs remains unclear.

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