Molecular basis of basal cell carcinoma

Abstract

Basal cell carcinoma is the most common cancer, presenting low mortality but high morbidity, and it has as risk factor exposure to sunlight, especially UVB spectrum. The most important constitutional risk factors for basal cell carcinoma development are clear phototypes (I and II, Fitzpatrick classification), family history of basal cell carcinoma (30-60%), freckles in childhood, eyes and light hair. The environmental risk factor better established is exposure to ultraviolet radiation. However, different solar exposure scenarios probably are independent risk factors for certain clinical and histological types, topographies and prognosis of this tumor, and focus of controversy among researchers. Studies confirm that changes in cellular genes Hedgehog signaling pathway are associated with the development of basal cell carcinoma. The cellular Hedgehog signaling pathway is activated in organogenesis, but is altered in various types of tumors.

Recent Advances in Signaling Pathways Comprehension as Carcinogenesis Triggers in Basal Cell Carcinoma

“…TP53 encodes for the p53 protein, one of the most important regulators of the cell cycle. Mutations in TP53 seem to be involved in the initiation of the malignant process but also in tumor progression [ 13 ].…”

“…Under normal conditions, the hair follicle and the skin are the only two regions where the Hh signaling displays post-embryonic activity. Hh signaling is also active in stem cells and in tissues undergoing regeneration, having an important role in wound healing [ 13 ]. The ectopic activation of the Hh pathway contributes to tumorigenesis, metastasis and resistance to therapy [ 34 ].…”

“…In other words, Hh ligands are the initiators of Hh pathway, PTCH1 operates as a negative regulatory receptor, and SMO as a positive regulatory receptor. In the absence of Hh ligands, PTCH1 binds to SMO preventing the pathway activation [ 13 , 44 ]. GLI transcription factors are blocked into the cytoplasm by various proteins acting as mediators.…”

Revisión sistemática del carcinoma basocelular

“…En el año 1827, el Dr. Arthur Jacob lo denomina "ulcus rodens" por su similitud con una mordedura de rata, y fue descrito por parte del mismo como una úlcera de crecimiento muy lento en la cara, con bordes característicos, incurable sin su erradicación y sin lesiones linfáticas. Para el año 1903, se hizo cambio de su nombre a "epitelioma basocelular o de células basales" por el dr. krompecher (4). posteriormente se denominó carcinoma basocelular (CBC) o Carcinoma de Células Basales por los dermatólogos anglosajones, esto para la constancia de que era una neoplasia maligna (3).…”

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“…La exposición a la radiación ultravioleta es el principal factor de riesgo para desarrollo de CBC, ocasiona mutación del gen PTCH y sobreactivación de la vía de señalización Sonic hedgehog. 1,7,8 Aunque se manifiesta a partir de los 60 años de edad, se observan cada vez más casos de CBC en individuos menores de 40 años de edad no asociado a síndromes genéticos de predisposición a aparición Rombo, tricoepiteliomas múltiples familiares, entre otros . 1,6 El CBC es más frecuente en el sexo masculino.…”