FGFR2 and NOTCH1 Expression Inversely Correlated in Progressive Cutaneous Carcinogenesis in an Experimental Mouse Model.

Cutaneous squamous cell carcinoma (cSCC) is a common and increasingly prevalent form of skin cancer, posing significant health challenges. Understanding the molecular mechanisms involved in cSCC progression is crucial for developing effective treatments. The primary aim of this research was to evaluate the activation of NOTCH1 and FGFR2 oncogenes in inducing skin cancer in FVB/N mice through a stepwise chemical process. Forty female FVB/N mice, aged four weeks, were randomly divided into a control group (n = 8) and two experimental groups (group A: n = 16, group B: n = 16). This study involved subjecting the groups to a two-stage carcinogenesis procedure. This included an initial application of 97.4 nmol DMBA on shaved skin on their backs, followed by applications of 32.4 nmol TPA after thirteen weeks for group A and after twenty weeks for group B. The control group did not receive any treatment. Their skin conditions were monitored weekly to detect tumor development. After the experiment, the animals were euthanized for further tissue sampling. The examination of skin lesions in the experimental groups showed a correlation with tumor progression, ranging from dysplasia to carcinoma. Tumor samples were assessed both histologically and immunohistochemically. Notably, FGFR2 expression was higher in benign, precancerous, and malignant tumors compared to normal tissue. NOTCH1 expression was only elevated in benign tumors compared to normal tissue. This study demonstrates a clear correlation of FGFR2 expression and the progression of cutaneous neoplasms, while NOTCH 1 expression is inversely correlated in FVB/N mice. This suggests an early involvement of these oncogenes in the development of skin tumors.

EGFR and HER-2 oncogenes expression in an experimental model of two-stage chemically induced carcinogenesis in mouse skin.

The aim of the study was to investigate the expression of EGFR and HER-2 oncogenes using an experimental two stage chemically induced carcinogenesis protocol on the dorsal skin in FVB/N mice. Forty female FVB/N mice 4 weeks old, were grouped into one control (n = 8) and two experimental groups (Group A: n = 16, Group B: n = 16) following a randomization process. Two-stage carcinogenesis protocol, was implicated, including an initial treatment with 97.4 nmol DMBA on their shaved dorsal skin and subsequent treatments of 32.4 nmol TPA applications after 13 weeks for Group A and after 20 weeks for Group B. The control group C, received no treatment. Skin was examined weekly for tumor development. Post-experiment, animals were euthanized for tissue analysis. The histological status of the skin lesions in the experimental groups corresponded well with tumour advancement (from dysplasia to poorly-differentiated carcinoma). Tumour sections were evaluated histologically and immunohistochemically. EGFR expression was found significantly higher in precancerous and malignant tumours (p = 042 and p = 008 respectively), while tended to be higher in benign tumours (p = 079), compared to normal histology. Moreover, mean percentage of EGFR positive expression in malignant tumours was significantly higher than in benign tumours (p < 001). HER-2 expression was found significantly higher in precancerous and malignant tumours (p = 042 and p = 015 respectively), while tended to be higher in benign tumours (p = 085), compared to normal histology. Furthermore, mean percentage of HER-2 positive expression in malignant tumours was significantly higher than in benign tumours (p = 005). The study demonstrated that in FVB/N mice subjected to a two-stage chemically induced carcinogenesis protocol, there was a significant increase in the expression of EGFR and HER-2 oncogenes in precancerous and malignant skin lesions compared to normal tissue. This suggests a potentially early role of these oncogenes in the progression of skin tumours in this model.

Collision tumor of malignant tumors of the skin: dermal squamomelanocytic tumor coexisting with basal cell carcinoma-a rare case.

Collision tumors are neoplasms coexisting in the some anatomical area. The most common combination is melanocytic nevus with basal cell carcinoma. Melanocytic nevus with basal cell carcinoma constitutes the most common cutaneous combination. Co-existence of two malignant neoplasms is extremely rare. We describe the case of a 69-year-old man who was admitted to our hospital with a nodular mass on the back. We performed an excisional biopsy that revealed collision tumor, consisting of basal cell carcinoma along with mixed melanosquamous carcinoma. Subsequently, wide excision with sentinel node biopsy was performed. The sentinel node was negative. The patient did not receive any ongologic therapy.

Association study indicates combined effect of interleukin-10 and angiotensin-converting enzyme in basal cell carcinoma development.

Cytokines involved in inflammatory and immune response have been associated with risk for development of basal cell carcinoma (BCC). In this study, three functional DNA polymorphisms affecting gene expression were investigated in 54 BCC patients and 111 healthy controls: interleukin-1b (IL-1b) +3953C/T, interleukin-10 (IL-10) - 1082G/A and angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphisms. Significant increase of the variant alleles was observed in IL-10 - 1082G (P = 0.019) and in ACE D (P = 0.003) in BCC patients in comparison to controls. Multivariate logistic regression models evaluated the contribution of homozygous and heterozygous variant polymorphisms to the risk for BCC development. The studied polymorphisms influencing the expression of IL-10 and ACE genes were recognized as potential predictive factors for BCC. These findings suggest a possible molecular mechanism leading to BCC development that is likely to involve the activation of angiotensin receptors in combination with increased plasma levels of IL-10 in patients.