Study of the PI3K / AKT pathway and the loss of heterozygosity of the tumor suppressor gene Pten in potentially malignant lesions and oral squamous cell carcinoma
| Autor: | Chaves, Filipe Nobre |
|---|---|
| Přispěvatelé: | Pereira, Karuza Maria Alves |
| Jazyk: | portugalština |
| Rok vydání: | 2017 |
| Předmět: | |
| Zdroj: | Repositório Institucional da Universidade Federal do Ceará (UFC) Universidade Federal do Ceará (UFC) instacron:UFC |
| Popis: | Oral Potentially Malignant Lesions (PML) is a group of lesions that present a risk for the development of Oral Squamous Cell Carcinoma (OSSC), including Oral Epithelial Dysplasia (OED). PTEN is a tumor suppressor gene of the PI3K / AKT pathway, which is one of the more deregulated pathways of cancer. However, it is still unknown how this pathway is involved in the malignant transformation process of PML. The heterozygosity loss (LOH) profiles were validated as predictors of malignant transformation of OED and in carcinomas from several locations. In addition, it is not known whether the allelic loss of PTEN also occurs in malignant lesions in the early stage and, as well, is involved as one of the mechanisms of oral carcinogenesis. In addition, it is suggested that allelic loss of PTEN also occurs in the early stages of malignant lesions and is involved in the mechanisms of oral carcinogenesis. Thus, a better understanding of the role of pathway in the process of oral carcinogenesis is necessary, searching for possible molecular markers for oral cancer. Objective: To evaluate the PI3K/AKT pathway in the malignant transformation process of PML and CEOs, through the immunoexpression of pAKT, pJNK, FoxO3a and Ki-67, besides performing immunomolecular evaluation of the PTEN tumor suppressor gene in DEO and CEO samples, with different histological types of malignancy, through the analysis of LOH in two chromosomal regions and immunohistochemical evaluation of the PTEN protein. Materials and methods: Tissue samples of 20 cases of OSCCs, 20 OEDs and 5 cases of normal oral mucosa were subjected to immunohistochemistry reactions for anti-p-AKT, anti-p-JNK, anti-FoxO3a and anti-Ki-67 antibodies. It was analyzed quantitative (number of immunostained cells) and qualitative (immunostaining intensity) parameters in different cell immunostaining sublocations. For molecular analysis, formalin-fixed paraffin-embedded samples of 19 OED and 16 OSCC were included to immunohistochemistry and LOH analysis. For the immunohistochemical study, 5 random fields with greater immunoreactivity were photomicrographed and it was done the count of keratinocytes which showed cytoplasmic and nuclear staining. For LOH analysis, 2 polymorphic microsatellite markers (AFMA086WG9 and D10S1765) localizing to chromosomes 10 were used to detect LOH. Results: Nuclear p-AKT was observed significantly greater immunostaining in CCEOs (21.2 ± 19.0) than in dysplasias (7.9 ± 8.1) and control (1.8 ± 4.7) (p = 0.002). Immunostaining of strong nuclear p-JNK was greater in controls (48.3 ± 13.7) than in OEDs (11.0 ± 10.3) and OSCCs (1.1 ± 1.3) (p |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|