Immunohistochemical analysis of the mechanistic target of rapamycin and hypoxia signalling pathways in basal cell carcinoma and trichoepithelioma

Background: Basal cell carcinoma (BCC) is the most common cancer in Caucasians. Trichoepithelioma (TE) is a benign neoplasm that strongly resembles BCC. Both are hair follicle (HF) tumours. HFs are hypoxic microenvironments, therefore we hypothesized that hypoxia-induced signalling pathways could be involved in BCC and TE as they are in other human malignancies. Hypoxia-inducible factor 1 (HIF1) and mechanistic/mammalian target of rapamycin (mTOR) are key players in these pathways. Objectives: To determine whether HIF1/mTOR signalling is involved in BCC and TE. Methods: We used immunohistochemical staining of formalin-fixed paraffin-embedded BCC (n = 45) and TE (n = 35) samples to assess activity of HIF1, mTORC1 and their most important target genes. The percentage positive tumour cells was assessed manually in a semi-quantitative manner and categorized (0%, 80%). Results: Among 45 BCC and 35 TE examined, expression levels were respectively 81% and 57% (BNIP3), 73% and 75% (CAIX), 79% and 86% (GLUT1), 50% and 19% (HIF1 alpha), 89% and 88% (pAKT), 55% and 61% (pS6), 15% and 25% (pMTOR), 44% and 63% (PHD2) and 44% and 49% (VEGF-A). CAIX, Glut1 and PHD2 expression levels were significantly higher in TE when only samples with at least 80% expression were included. Conclusions: HIF and mTORC1 signalling seems active in both BCC and TE. There are no appreciable differences between the two with respect to pathway activity. At this moment immunohistochemical analyses of HIF, mTORC1 and their target genes does not provide a reliable diagnostic tool for the discrimination of BCC and TE

Pain in photodynamic therapy: mechanism of action and management strategies Dor na terapia fotodinâmica: mecanismo de ação e estratégias de manejo

Photodynamic therapy involves administration of a photosensitizing drug and its subsequent activation by irradiation with a light source at wavelengths matching the absorption spectrum of the photosensitizer. In many countries around the world, topical photodynamic therapy has been approved for treatment of cutaneous oncologic conditions such as actinic keratosis, Bowen's disease, and superficial basal cell carcinoma. Multicenter, randomized, controlled studies have confirmed its efficacy and superior cosmetic outcomes compared to conventional therapies. Nevertheless, this therapeutic method presents some adverse effects, such as erythema, edema, pigmentation, pustules, and pain. There is no doubt that pain is the most severe of the adverse effects, being sometimes responsible for definitive treatment interruption. The pain mechanism has not yet been fully understood, which makes complete pain control a challenge to be conquered. In spite of that, this literature review presents some useful pain management strategies as well as the most important pain-related factors in photodynamic therapy.<br>A terapia fotodinâmica consiste na administração de uma droga fotossensibilizante e sua subseqüente irradiação com uma fonte de luz de espectro correspondente ao do seu fotossensibilizador. Em diversos países do mundo, a terapia fotodinâmica tópica é aprovada para o tratamento de condições oncológicas cutâneas como queratoses actínicas, doença de Bowen e carcinoma basocelular superficial. Estudos multicêntricos controlados e randomizados confirmam sua eficácia e seus resultados cosméticos superiores em relação às terapias convencionais. No entanto, existem alguns efeitos adversos inerentes a esse método terapêutico, como eritema, edema, pigmentação, pústulas e dor. Essa última é, sem dúvida, a mais importante deles, chegando a ser responsável pela interrupção definitiva do tratamento em alguns casos. O mecanismo dessa dor permanece ainda não completamente entendido. Tal fato faz do controle total da dor durante a terapia fotodinâmica um desafio ainda a ser conquistado. Apesar disso, esta revisão apresenta algumas estratégias que podem ajudar os pacientes a tolerar melhor a terapia fotodinâmica, além de relacionar os principais fatores ligados à dor descritos na literatura