Squamous cell carcinomas arise from stratified squamous epithelia. Here, a comparative analysis based on recent studies defining the genetic alterations and composition of the stroma of oral and cutaneous squamous cell carcinomas (OSCC and CSCC, respectively) was performed. Both carcinomas share some but not all histological and genetic features. This review was focused on how mutations in tumor suppressor genes and protooncogenes cooperate to determine the differentiation, aggressiveness, and metastatic potential of OSCC and CSCC. In fact, driver mutations in tumor suppressor genes are more frequently observed in OSCC than CSCC. These include mutations in TP53 (encoding pP53 protein), CDKN2A (encoding cyclin dependent kinase inhibitor 2A), FAT1 (encoding FAT atypical cadherin 1), and KMT2D (encoding lysine methyltransferase 2D), with the exception of NOTCH (encoding Notch receptor 1), whose mutation frequency is lower in OSCC compared to CSCC. Finally, we describe the differential composition of the tumor microenvironment and how this influences the aggressiveness of each tumor type. Although both OSCC and CSCC tumors are highly infiltrated by immune cells, high levels of tumor-infiltrating lymphocytes (TILs) have been more frequently reported as predictors of better outcomes in OSCC than CSCC. In conclusion, OSCC and CSCC partially share genetic alterations and possess different causal factors triggering their development. The tumor microenvironment plays a key role determining the outcome of the disease.
Oxidative stress is a harmful effect induced on the skin by polycyclic aromatic hydrocarbons (PAH), including benzo[a]pyrene (BaP) air pollutants. This effect is amplified by the additive damaging effect of the sun, especially through the UVA light component. Besides being one of the main compounds that make up air pollution, BaP can also be found in tar, tobacco smoke, and various foods. In addition to its direct carcinogenic potential, BaP can act as a photosensitizer absorbing sunlight in the UVA range and thus generating ROS and 8-hydroxy-2′-deoxyguanosine (8-OHdG). Fernblock® (FB) is an aqueous extract from the leaves of Polypodium leucotomos that has been proven to exert photoprotective and antioxidant effects on skin cells. In this study, we evaluate the potential of FB to prevent the damage induced by a combination of BaP and UVA light on human keratinocyte and mouse melanocyte cell lines (HaCaT and B16-F10, respectively). In particular, we have analyzed the capacity of FB to counteract the alterations caused on cellular morphology, viability, oxidative stress and melanogenic signaling pathway activation. Our data indicate that FB prevented cell damage and reduced oxidative stress and melanogenic signaling pathway activation caused by a combination of BaP and UVA light irradiation. Altogether, our findings support the fact that FB is able to prevent skin damage caused by the exposure to a combination of UVA and the air pollutant BaP.
A squamous odontogenic tumor (SOT) is an epithelial locally benign neoplasia derived from the periodontium of the jaws. It is considered a lesion of low incidence. Predominantly, it affects the mandible, although both jaw bones may be involved. Here, we discuss the malignant clinical evolution of an SOT lesion in an 80-year-old female patient. The patient exhibited an expansive triangular lesion at the inferior right quadrant. Surgery was performed and an SOT was diagnosed (2019). Two years after, the lesion grew, and the analysis of the biopsy revealed SOT malignization with pleomorphic atypical squamous cells, characteristics of a squamous cell carcinoma (2021). Massive DNA sequencing of formalin-fixed–paraffin-embedded specimens of the initial and relapsed tumors indicated pathogenic mutations in RET and POLE genes in both tumors, loss of ALK, and gain of CDKN1B and MAP2K in the relapse. In addition, the clinical, radiographic, and microscopic features of this neoplasm are discussed and compared with those already published. The case presented contributes to the better understanding of this SOT tumor entity and to indicates its malignant evolution, together with its biological behavior and its histologic, clinical, and radiographic features. Also, it aims to stress the importance of deeper genetic analyses in rare diseases to uncover mutations that help to select a personalized treatment.
Tumor microenvironment (TME) plays a fundamental role in the progression as well as in the resistance to therapies in oral squamous carcinomas (OSCC). Cancer-associated fibroblasts (CAFs), despite being the most prominent non-immune cell types of stroma in cancer, are poorly characterized. CAFs play a fundamental role in modulating the cell cycle, stemness, and epithelial-mesenchymal transition (EMT) and are capable of conferring resistance to different types of therapies, including chemo/radiotherapy, EGFR inhibitors, and anti-PD-1/PD-L1 checkpoint inhibitors. To do this, CAFs secrete extracellular matrix components, where tumor cells are immersed, and release growth factors, chemokines, and metabolites that affect tumor cell properties. Therefore, they are associated with poor prognosis. Here, we summarize our current understanding of CAFs and their involvement in the OSCC resistance therapies, and we propose potential actions for targeting these cells.
Background: Considering the significant impact on quality of life and the chronic nature of temporomandibular dysfunction (TMD), seeking healthcare is also part of the reality of individuals with this disorder. However, cultural differences and similarities in the experiences of individuals with TMD have not yet been investigated. This study aimed to describe and compare the experiences, beliefs, and sociocultural factors of Brazilian and Spanish individuals with TMD, focusing on their perceptions of the disorder, diagnostic pathways, information-seeking behaviors, and treatment expectations. Methods: A descriptive qualitative study was conducted. A purposive sample of 50 participants (25 Brazilian, 25 Spanish), aged 18–50 and diagnosed with TMD according to DC/TMD criteria, was recruited. Data were obtained through semi-structured interviews and analyzed using thematic analysis. Results: Six themes emerged, revealing both similarities and differences between the groups. Brazilian participants reported uncertainty about which professional to consult and difficulty accessing specialized care. In contrast, Spanish participants frequently sought physical therapists as their first option and identified them as primary sources of information. Beliefs about TMD etiology varied across samples. Treatment expectations also differed. Brazilians emphasized the difficulty of obtaining effective care, while Spanish participants perceived physiotherapy as being limited to muscular disorders. Perceptions of occlusal splint effectiveness showed variation between the groups. Conclusions: These findings underscore the necessity of culturally sensitive approaches to patient care that address not only clinical aspects, but also the sociocultural context that influences health behaviors.