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| Author(s): |
Ana Flávia de Mattos Costa
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas |
| Defense date: | 2014-02-20 |
| Examining board members: |
Albina Messias de Almeida Milani Altemani;
Ana Paula Dias Demasi;
Fábio Rogério;
Pablo Agustin Vargas;
Ricardo Santiago Gomez
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| Advisor: | Marinus Antonius Jacobus Hermsen; Albina Messias de Almeida Milani Altemani |
| Abstract | |
Adenoid cystic carcinomas can occasionally undergo dedifferentiation, a phenomenon also referred to as high-grade transformation. However, cases of adenoid cystic carcinomas have been described showing transformation to adenocarcinomas that are not poorly differentiated, indicating that high-grade transformation may not necessarily reflect a more advanced stage of tumor progression, but rather a transformation to another histological form, which may encompass a wide spectrum of carcinomas in terms of aggressiveness. The aim of this study was to gain more insight in the biology of this pathological phenomenon. Firstly, we investigated expression of proteins regulated by hypoxia (HIF-1?, VEGF, GLUT-1 and CD105), given that hypoxia contributes to aggressive tumor behavior and can also promote a dedifferentiated phenotype in certain types of cancer. Hereafter, we analyzed an important point of interest of adenoid cystic carcinoma with high-grade transformation that is its proposed poor prognosis to be comparable to or even worse than solid subtype. Therefore, we compared the genetic changes of transformed and solid subtype adenoid cystic carcinomas and correlated the results to their clinico-pathological features. In addition, in another work, we used microarray comparative genomic hybridization to compare the genetic profiles of both histological components of adenoid cystic carcinomas with high-grade transformation. Special attention was given to chromosomal translocation and protein expression of MYB, recently being considered to be an early and major oncogenic event in adenoid cystic carcinomas. Our data showed that transformed adenoid cystic carcinoma with high-grade transformation may present a genetic complexity similar to the solid subtype and, also that the process of high-grade transformation is not always be accompanied by an accumulation of genetic alterations; which indicate a parallel progression of the two histological components of transformed adenoid cystic carcinoma. In contrast to MYB protein expression, MYB/NFIB translocation is not necessarily an early event and, as hypoxia, not fundamental for the development of these tumors. Finally, the study that comes from of adenoid cystic carcinoma with high-grade transformation also allowed us to do a review about it. In this study we made an overview of the latest concepts in histopathological classification of salivary gland tumors with dedifferentiation / high-grade transformation described in the literature. Highlight was also given to immunohistochemical and genetic findings that can help in the diagnosis of each of these tumors (AU) | |
| FAPESP's process: | 09/54377-2 - Identification of genetic and epigenetic alterations in adenoid cystic carcinoma with high-grade transformation |
| Grantee: | Ana Flávia de Mattos Costa |
| Support Opportunities: | Scholarships in Brazil - Doctorate |