Photoexposition discriminates Notch 1 expression in human cutaneous squamous cell carcinoma
| Autor: | Claudia Di Serio, Francesca Tarantini, John Panelos, Daniela Massi, Silvia Pellerito, Milena Paglierani, Nicola Pimpinelli, Vincenza Maio, Marco Santucci |
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| Rok vydání: | 2008 |
| Předmět: |
Adult
Male Pathology medicine.medical_specialty Skin Neoplasms Ultraviolet Rays Notch signaling pathway Down-Regulation Biology Pathology and Forensic Medicine Notch Family Recurrence medicine Humans Basal cell carcinoma Receptor Notch1 Notch 1 Aged Aged 80 and over Cancer Middle Aged medicine.disease Immunohistochemistry Up-Regulation Gene Expression Regulation Neoplastic Solar keratosis Carcinoma Basal Cell Carcinoma Squamous Cell Disease Progression Papilloma Female Skin cancer Precancerous Conditions |
| Zdroj: | Modern Pathology. 21:316-325 |
| ISSN: | 0893-3952 |
| DOI: | 10.1038/modpathol.3801007 |
| Popis: | The Notch signaling pathway may play opposing roles in cancer. It can be oncosuppressive or protumoral, depending on the cellular and tissue context. In skin cancer, Notch 1 expression is downregulated, thus supporting the hypothesis of an oncosuppressive role in cutaneous carcinomas. However, as members of the Notch family undergo downregulation upon exposure to UV irradiation, we wondered whether Notch 1 expression in skin carcinomas may be governed by additional factors, including UV exposure. We investigated the expression of Notch 1 and its ligands, Jagged 1, Jagged 2 and Delta-like 1, by immunohistochemistry in a series of premalignant and invasive cutaneous carcinomas, including 4 solar keratoses, 5 Bowen's disease, 5 squamous cell carcinomas on sun-exposed skin, 6 squamous cell carcinomas on sun-protected genital skin and 14 basal cell carcinomas of different histotypes (nodular, superficial type, sclerodermiform/infiltrating and baso-squamous). Expression of Notch 1 was decreased in solar keratoses and invasive squamous cell carcinomas localized on sun-exposed skin. In contrast, marked Notch 1 staining was observed in extragenital Bowen's disease as well as in genital (penile) human papilloma virus-related in situ and invasive squamous cell carcinomas. A diffuse Notch 1 staining was detected in nodular and superficial basal cell carcinomas while sclerodermiform/infiltrating and baso-squamous basal cell carcinomas showed a low to absent Notch 1 expression. Jagged 1, Jagged 2 and Delta-like 1 proteins were expressed in all tissues examined. Present findings show divergent expression of Notch 1 in skin cancer, depending on anatomical site and tumor histotype. Thus, whereas in UV-related squamous cell photocarcinogenesis Notch 1 downregulation could mirror a tumor suppressor function of the receptor, in sun-protected squamous cell carcinomas Notch 1 was upregulated. Furthermore, Notch 1 expression was minimal in basal cell carcinoma subtypes correlated with risk of recurrence (sclerodermiform/infiltrating and baso-squamous) in comparison with nodular and superficial types. |
| Databáze: | OpenAIRE |
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