Prognostic Factors of Surgically Treated Pancreatic Cancer. Doctoral Thesis

Abstract

According to data provided by the Centre of Health Economics of Latvia, the incidence of pancreatic tumours is increasing: there were 360 diagnosed cases in 2007 but 405 cases in 2010. Similar growth of incidence has been observed worldwide. The 5-year survival of pancreatic cancer is 15% for patients receiving the best possible treatment, including radical surgical treatment, but in the total group of pancreatic cancer, the 5-year survival rate is only 5%. In addition, the treatment results have not improved significantly over last 30 years. Therefore, it is essential to study the biological potential and its underlying mechanisms of pancreatic cancer in order to define possible treatment target molecules and to specify individual prognosis of each patient. The aim of the research work is to detect the morphological and immune-histochemical profile of potentially radically operated pancreatic ductal adenocarcinoma (PDAC) and pancreatic endocrine tumours (PETs) and the clinical and prognostic importance of it in local patients. Materials and methods. This study was performed as a retrospective, evidence-based morphological and immunohistochemical investigation of potentially radically operated PDACs and PETs, including 14 morphological and 21 immunohistochemical parameters and survival analysis by applying a wide scope of descriptive and analytic statistic methods. The research was carried out in accordance with the Declaration of Helsinki and received approval from the Committee of Ethics of Riga Stradins University. Results. In the study, 78 cases of potentially radically operated PDAC and 16 cases of PET were selected. The mean age was 63.4 years for PDAC and 59.4 years for PET patients. PDAC had the following characteristics: large tumour size (mean size 3.6 cm), frequent pT3 – 98.7%, pN1 – 67.5%, moderate or poor differentiation in 46.2% and 35.9% of cases, perineural invasion – 87.2% and R1 – 57.5% of cases. PET were characterised by less aggressive characteristics: pT3 – 37.5%, pN1 – 20.0%, R1 – 27.3% of cases; well differentiated endocrine tumours with unclear behaviour predominated (56.3%). Comparing neoplastic cells with the non-neoplastic counterparts, CK 20, CK 5/6, COX-2, Ki-67, p53, p21, cyclin D1, chromogranin A and vimentin were up-regulated in PDAC, but CK 7, CK 19, p63, vimentin, COX-2, Ki-67 and CD44 in PET. In contrast, expression of p27, CK 7, CK 19 and CD56 was lost in PDAC cases. The median overall survival after potentially radical operation was 11.0 months for PDAC patients, but among PET patients 2/ 14 patients died after 1 and 15 months. Tumour invasion in large blood vessels (p = 0.013), necrosis (p = 0.001), increased expression of vimentin (p = 0.002) and CD44 (p = 0.018), decreased expression of p27 (p = 0.003) showed prognostic significance in PDAC cases. Conclusion. The overall survival after potentially radically treated PDAC is poor. At the time of diagnostics, the tumours are already large. PDAC is characterised by high invasiveness and thus able to spread. By immunohistochemical evaluation, the epithelial-mesenchymal transition, increased CD44 expression and loss of p27 had prognostic significance. PET are less aggressive, but decreased E-cadherin expression, up-regulation of CK 19 and vimentin expression can indicate tumour progression and spreading.