Publicação
Contribution to the study of prognostic factors in canine oral squamous cell carcinoma
| Resumo: | The main goal of this clinical work was to contribute to the study of oral squamous cell carcinoma (OSCC) in the dog with regards to molecular and differentiation events, and their relationship with the tumor’s biological behavior – impact on the staging, prognosis or treatment. From the assessment of histological differentiation and proliferation index in a 36 OSCC case series, it was possible to identify a significant association between the proliferating cell nuclear antigen (PCNA) and Ki-67, distribution pattern and histological differentiation. PCNA expression was significantly higher than Ki-67 and a higher proliferation index was associated with poorly differentiated OSCC, resembling what is observed in humans. With regards to intra-oral locations, poorly differentiated tumors were significantly associated with the tonsillar location. Proliferation index was not associated with any of the intra-oral locations evaluated, but it was found that metastatic lymph nodes were significantly associated with OSCC with higher poliferation index. OSCC prognosis was assessed in a 13 case series where the age of the animal and tumor size, location, grade and proliferation were evaluated as post surgical prognostic factors. All cases were standardized – CT staged and clinically managed over a period of 2 years, with bone invasion, no lymphatic invasion nor distant metastasis. The results obtained indicated that grade and proliferation index were related with post operatory prognosis. Animals with high-grade tumors had shorter disease free survival times when compared to intermediate grade tumors. Also animals with high-grade tumors and with high PCNA proliferation index showed a significantly worse post-surgical prognosis. The immunohistochemical expression of the cell adhesion molecule E-cadherin and p63 protein were assessed and related with histological and clinical features at time of diagnosis in a 22 case series. Changes in p63 and E-cadherin expression seem to be frequent molecular events in canine OSCC. It was observed that p63 was overexpressed in all cases and E-cadherin was found to be underexpressed in most cases. Furthermore, p63 expression was related to the proliferation and there were different expression patterns related to tumor grade. None of the histological or immunohistochemical parameters were associated with tumor size, bone invasion or lymph node metastasis. More than the contribution to the knowledge of some of the molecular events involved in this tumor, this work explores the clinical applicability of such markers, especially proliferation, in a practical veterinary clinical setting, ilustrated in this work with one case report. This thesis also explores the potential use of the dog as a model in comparative oncology studies. |
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| Autores principais: | Mestrinho, Lisa Alexandra Pereira |
| Assunto: | Oral squamous cell carcinoma Canine Prognostic factors Ki-67 PCNA E-cadherin Carcinoma oral das células escamosas Cão Fatores de prognóstico Ki-67 p63 Caderina-E |
| Ano: | 2016 |
| País: | Portugal |
| Tipo de documento: | tese de doutoramento |
| Tipo de acesso: | acesso restrito |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | The main goal of this clinical work was to contribute to the study of oral squamous cell carcinoma (OSCC) in the dog with regards to molecular and differentiation events, and their relationship with the tumor’s biological behavior – impact on the staging, prognosis or treatment. From the assessment of histological differentiation and proliferation index in a 36 OSCC case series, it was possible to identify a significant association between the proliferating cell nuclear antigen (PCNA) and Ki-67, distribution pattern and histological differentiation. PCNA expression was significantly higher than Ki-67 and a higher proliferation index was associated with poorly differentiated OSCC, resembling what is observed in humans. With regards to intra-oral locations, poorly differentiated tumors were significantly associated with the tonsillar location. Proliferation index was not associated with any of the intra-oral locations evaluated, but it was found that metastatic lymph nodes were significantly associated with OSCC with higher poliferation index. OSCC prognosis was assessed in a 13 case series where the age of the animal and tumor size, location, grade and proliferation were evaluated as post surgical prognostic factors. All cases were standardized – CT staged and clinically managed over a period of 2 years, with bone invasion, no lymphatic invasion nor distant metastasis. The results obtained indicated that grade and proliferation index were related with post operatory prognosis. Animals with high-grade tumors had shorter disease free survival times when compared to intermediate grade tumors. Also animals with high-grade tumors and with high PCNA proliferation index showed a significantly worse post-surgical prognosis. The immunohistochemical expression of the cell adhesion molecule E-cadherin and p63 protein were assessed and related with histological and clinical features at time of diagnosis in a 22 case series. Changes in p63 and E-cadherin expression seem to be frequent molecular events in canine OSCC. It was observed that p63 was overexpressed in all cases and E-cadherin was found to be underexpressed in most cases. Furthermore, p63 expression was related to the proliferation and there were different expression patterns related to tumor grade. None of the histological or immunohistochemical parameters were associated with tumor size, bone invasion or lymph node metastasis. More than the contribution to the knowledge of some of the molecular events involved in this tumor, this work explores the clinical applicability of such markers, especially proliferation, in a practical veterinary clinical setting, ilustrated in this work with one case report. This thesis also explores the potential use of the dog as a model in comparative oncology studies. |
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