Endocrine pancreatic tumors: factors correlated with survival

Tomassetti, Paola; Campana, Davide; Piscitelli, L; Casadei, Riccardo; Santini, Donatella; Nori, Francesca; Morselli-Labate, Antonio Maria; Pezzilli, Raffaele; Corinaldesi, Roberto

doi:10.1093/annonc/mdi358

Cited by 182 publications

(99 citation statements)

References 22 publications

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“…The study was performed with the aim of deciphering alterations potentially related to the progression of this disease, and of providing a source of possible biomarkers and/or molecular targets. The characteristics of our samples (Ki-67 >2, primary size !3 cm), together with the presence of liver metastases and the progression of disease in each single patient, were all known to be predictive of poor prognosis , Tomassetti et al 2005, with both biotherapy and chemotherapy being poorly effective (O'Toole et al 2004, Oberg & Eriksson 2005, as confirmed by the outcome of five of the seven patients we have had under care in the follow-up period.…”

Section: Discussionmentioning

confidence: 61%

“…Although considered to be 'indolent' tumours, at the time of diagnosis almost two-thirds of NF PETs present with liver metastases, which is the main factor determining the patients' outcome , Tomassetti et al 2005). In addition, the different spontaneous behaviour of PETs (stable or progressive disease) plays a crucial role in their natural history.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Gene expression profiles of progressive pancreatic endocrine tumours and their liver metastases reveal potential novel markers and therapeutic targets

Capurso¹,

Lattimore²,

Crnogorac-Jurčević³

et al. 2006

Endocr Relat Cancer

101

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The intrinsic nature of tumour behaviour (stable vs progressive) and the presence of liver metastases are key factors in determining the outcome of patients with a pancreatic endocrine tumour (PET). Previous expression profile analyses of PETs were limited to non-homogeneous groups or to primary lesions only. The aim of this study was to investigate the gene expression profiles of a more uniform series of sporadic, non-functioning (NF) PETs with progressive disease and, for the first time, their liver metastases, on the Affymetrix human genome U133A and B GeneChip set. Thirteen NF PET samples (eight primaries and five liver metastases) from ten patients with progressive, metastatic disease, three cell lines (BON, QGP and CM) and four purified islet samples were analysed. The same samples were employed for confirmation of candidate gene expression by means of quantitative RT-PCR, while a further 37 PET and 15 carcinoid samples were analysed by immunohistochemistry. Analysis of genes differentially expressed between islets and primaries and metastases revealed 667 up-and 223 down-regulated genes, most of which have not previously been observed in PETs, and whose gene ontology molecular function has been detailed. Overexpression of bridging integrator 1 (BIN1) and protein Z dependent protease inhibitor (SERPINA10) which may represent useful biomarkers, and of lymphocyte specific protein tyrosine kinase (LCK) and bone marrow stromal cell antigen (BST2) which could be used as therapeutic targets, has been validated. When primary tumours were compared with metastatic lesions, no significantly differentially expressed genes were found, in accord with cluster analysis which revealed a striking similarity between primary and metastatic lesions, with the cell lines clustering separately. We have provided a comprehensive list of differentially expressed genes in a uniform set of aggressive NF PETs. A number of dysregulated genes deserve further in-depth study as potentially promising candidates for new diagnostic and treatment strategies. The analysis of liver metastases revealed a previously unknown high level of similarity with the primary lesions.

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Section: Discussionmentioning

confidence: 61%

Section: Introductionmentioning

confidence: 99%

Gene expression profiles of progressive pancreatic endocrine tumours and their liver metastases reveal potential novel markers and therapeutic targets

Capurso¹,

Lattimore²,

Crnogorac-Jurčević³

et al. 2006

Endocr Relat Cancer

101

View full text Add to dashboard Cite

show abstract

“…Indeed, differentiation of GEP NET classified as poorly compared with well-differentiated (WD) carcinoma (Johnson et al 1986, Greenberg et al 1987, Madeira et al 1998, Travis et al 1998, Rindi et al 1999, Lim et al 2005, Panzuto et al 2005, Asamura et al 2006, Faggiano et al 2007, Lepage et al 2007, Pape et al 2008 and stage (Lo et al 1996, Pelosi et al 1996, Burke et al 1997, Madeira et al 1998, Kirshbom et al 1999, Rindi et al 1999, Shebani et al 1999, Onaitis et al 2000, Quaedvlieg et al 2001, Rigaud et al 2001, Solorzano et al 2001, Hochwald et al 2002, Plöckinger et al 2004, Panzuto et al 2005, Tomassetti et al 2006, Baudin 2007, Pape et al 2008 as long been recognized the strongest prognostic parameters before the primary location. More recently, lymph node metastases (Hellman et al 2002, Cardillo et al 2004, Lim et al 2005, Tomassetti et al 2005, Baudin 2007, García-Yuste et al 2007, Rea et al 2007, Pape et al 2008 and proliferative index have emerged as major determinant of prognosis in GEP tumors of the lung (Travis et al 1998, Beasley ...…”

Section: Introductionmentioning

confidence: 99%

Prognostic factors influencing survival from metastatic (stage IV) gastroenteropancreatic well-differentiated endocrine carcinoma

Durante¹,

Boukheris²,

Dromain³

et al. 2009

Endocrine-Related Cancer

104

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Survival of metastatic gastroenteropancreatic well-differentiated endocrine carcinoma (GEP WDEC) is not well characterized. We evaluated the long-term outcome and prognostic factors for survival in 118 patients with distant metastases from GEP WDEC. Inclusion criteria were 1) pathological review by a single pathologist according to the present WHO criteria, 2) absence of previous therapy apart from surgery, 3) complete morphological evaluation within 3 months including somatostatin receptor scintigraphy, and 4) follow-up at Gustave-Roussy Institute until death or study's end. Clinical, biological marker, and pathological parameters were analyzed in univariate and multivariate statistical models. Survival after the first complete imaging work-up of the metastatic disease was determined using Kaplan-Meier method. Overall, survival for 5 years after the diagnosis of metastatic disease was 54%. In multivariate analysis, age (hazard ratio (HR): 1.05, 95% confidence interval (CI): 1.01-1.08, PZ0.01), the number of liver metastases (HR: 3.4, 95% CI: 1.4-8.3, PZ0.01), tumor slope (HR: 1.1, 95% CI: 1.0-1.1, PZ0.001), and initial surgery (HR: 0.3, 95% CI: 0.1-0.8, PZ0.01) were predictive of survival. Five-year survival was 100%, 91% (95% CI, 51-98%), 62% (95% CI, 37-83%), and 9% (95% CI, 6-32%) when patients had 0, 1, 2, 3 or more poor prognostic features respectively. This study enables the stratification of metastatic GEP WDEC patients into distinct risk groups. These risk categories can be used to tailor therapeutic approaches and also to design and interpret clinical trials.

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“…PETs are classified as 'functioning' (F) or 'non-functioning' (NF) depending on the presence or absence of a syndrome due to excessive hormone secretion from cancer cells (Plockinger et al 2004). Although PETs are considered to be 'indolent' tumours, at the time of diagnosis approximately 60% of NF PETs patients have liver metastases, which represent the most important factor determining their outcome , Tomassetti et al 2005. In patients with metastatic, progressive PETs, therapy with somatostatin analogues is poorly effective, with only 27% response .…”

Section: Introductionmentioning

confidence: 99%

Src family kinase activity regulates adhesion, spreading and migration of pancreatic endocrine tumour cells

Florio¹,

Capurso²,

Milione³

et al. 2007

Endocr Relat Cancer

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Pancreatic endocrine tumours (PETs) are rare and 'indolent' neoplasms that usually develop metastatic lesions and exhibit poor response to standard medical treatments. Few studies have investigated pathways responsible for PET cell growth and invasion and no alternative therapeutic strategies have been proposed. In a recent microarray analysis for genes up-regulated in PETs, we have described the up-regulation of soluble Src family tyrosine kinases in this neoplasia, which may represent potentially promising candidates for therapy. Herein, we have investigated the expression and function of Src family kinases in PETS and PET cell lines. Western blot analysis indicated that Src is highly abundant in the PET cell lines CM and QGP-1. Immunohistochemistry and Western blot analyses showed that Src is up-regulated also in human PET lesions. Pharmacological inhibition of Src family kinases by the specific inhibitor PP2 strongly interfered with adhesion, spreading and migration of PET cell lines. Accordingly, the actin cytoskeleton was profoundly altered after inhibition of Src kinases, whereas even prolonged incubation with PP2 exerted no effect on cell cycle progression and/or apoptosis of PET cells. A transient increase in tyrosine phosphorylation of a subset of proteins was observed in QGP-1 cells adhering to the plate, with a peak at 75 min after seeding, when approximately 80% of cells were attached. Inhibition of Src kinases caused a dramatic reduction in the phosphorylation of proteins with different molecular weight that were isolated from the cell extracts by anti-phosphotyrosine immunoprecipitation or pull-down with the SH2 domain of Src. Among them, the docking protein p130Cas interacted with Src and is a major substrate of the Src kinases in QGP-1 cells undergoing adhesion. Our results suggest that Src kinases play a specific role during adhesion, spreading and migration of PET cells and may indicate therapeutical approaches directed to limiting the metastatic potential of these cells.

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Endocrine pancreatic tumors: factors correlated with survival

Abstract: Tumor resection, the absence of liver and lymph node metastases, and the presence of MEN 1 syndrome are related to a better survival rate. Radical surgery continues to have a central role in the therapeutic approach to endocrine tumors of the pancreas.

Cited by 182 publications

References 22 publications

Gene expression profiles of progressive pancreatic endocrine tumours and their liver metastases reveal potential novel markers and therapeutic targets

Gene expression profiles of progressive pancreatic endocrine tumours and their liver metastases reveal potential novel markers and therapeutic targets

Prognostic factors influencing survival from metastatic (stage IV) gastroenteropancreatic well-differentiated endocrine carcinoma

Src family kinase activity regulates adhesion, spreading and migration of pancreatic endocrine tumour cells

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