33 The results of the present study showed a significant increase of tryptase+ MCs in SCCs compared with normal lip. These findings agree with other results in the literature.34 and 35 On the other hand, Oliveira-Neto et al.36 found a decrease of tryptase+ Ceritinib MCs in oral squamous cell carcinoma (OSCC) and leukoplakia. Studies have pointed to an increase in the number of MCs, including tryptase+ ones, in solar radiation–exposed skin.9, 37, 38, 39 and 40 This may explain the

differences in MC densities found in SCCs and ACs compared with OSCCs. Chronic exposure to radiation, particularly UV, has been described as one of the main risk factors related to AC and SCC development.35 and 40 Our results also showed a significant increase of tryptase+ MCs in SCCs compared with ACs, unlike the findings of Costa et al.,34 where similar MC densities were found in both lesions. ACs present a variety of histologic changes that primarily include varying degrees of keratosis, solar elastosis, epithelium atrophy or hyperplasia, and the absence or presence of dysplasia.1 All cases studied by Costa et al. were classified as mild epithelial dysplasia, whereas in our study only 5 cases were so classified. That may explain the different MC densities observed

in ACs between these studies. In the present study, a higher MC density was observed in the stroma compared with the tumor parenchyma. MCs may accumulate in the stroma around the tumor and take part in the inflammatory reaction that happens at the tumor edge and in the local tumor immunity.5 Nevertheless, the increase of stromal Enzalutamide concentration tryptase+ MCs has also been reported as an important factor for tumor invasion on cancers in various anatomic sites.41 and 42 Therefore, these cells may contribute to the defense against tumors as well as to their progression. Our results also pointed to a significant increase in c-Kit+ MC density in SCCs and ACs compared with control samples. These findings differ from the results of Costa et al.34 who found a similar cell density for the 3 groups. c-Kit (CD 117) is a transmembrane receptor tyrosine kinase type III that acts in cellular signal transduction in various cell types. It is usually

activated by binding to its ligand, stem cell Org 27569 factor (SCF). In this scenario, it promotes phosphorylation and activation of the intracytoplasmic signaling cascade which is essential for embryogenesis, hematopoiesis, development, proliferation, and migration. c-Kit is expressed in normal human tissue, melanocytes, breast epithelium, interstitial cells of Cajal, and MCs. SCF stimulates directional motility of both mucosal and connective tissue–type MCs. It also plays a role in MC survival and activation via up-regulation of TNF-α, chemokine production, and the induction of histamine release.43 MCs are long-lived cells that can restart the cell cycle, proliferate, and be recruited after an appropriate stimulation. This stimulus may contribute to population expansion of these cells. Kim et al.