Tissue Biomarkers for Prognosis in Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-analysis

Abstract

Purpose: The management of pancreatic ductal adenocarcinoma (PDAC) continues to present a great challenge particularly with regard to prediction of outcome following pancreaticoduodenectomy. Molecular markers have been extensively investigated by numerous groups with the aim of enhancing prognostication; however, despite hundreds of studies that have sought to assess the potential prognostic value of molecular markers in predicting the clinical course following resection of PDAC, at this time, no molecular marker assay forms part of recommended clinical practice.Experimental Design: We conducted a systematic review and meta-analysis of the published literature for immunohistochemistry-based biomarkers of PDAC outcome. A dual search strategy was applied to the PubMed database on January 6, 2010, to identify cohort studies that reported associations between immunohistochemical biomarker expression and survival outcomes in PDAC, and conformed to the REMARK (REporting recommendations for tumor MARKer prognostic studies) criteria.Results: A total of 103 distinct proteins met all inclusion criteria. Promising markers that emerged for the prediction of overall survival included BAX (HR ¼ 0.31, 95% CI: 0.71-0.56), Bcl-2 (HR ¼ 0.41, 95% CI: 0.27-0.63), survivin (HR ¼ 0.46, 95% CI: 0.29-0.73), Ki-67: (HR ¼ 2.42, 95% CI: 1.87-3.14), COX-2 (HR ¼ 1.39, 95% CI: 1.13-1.71), E-cadherin (HR ¼ 1.80, 95% CI: 1.33-2.42), and S100 calcium-binding proteins, in particular S100A2 (HR ¼ 3.23, 95% CI: 1.58-6.62).Conclusions: We noted that that there was incomplete adherence to the REMARK guidelines with inadequate methodology reporting as well as failure to perform multivariate analysis. Addressing the persistent incomplete adoption of these criteria may eventually result in the incorporation of molecular marker assessment within PDAC management algorithms. Clin Cancer Res; 17(10); 3316-31. Ó2011 AACR.

Prognostic Factors after Curative Resection of Pancreatic Ductal Adenocarcinoma: a Retrospective Study

“…Ki-67 expression correlates with the tumour grade and lymph node metastasis [29]. It has also been stated that the expression of Ki-67 becomes prognostically significant if it exceeds 5% [6,7]. Our results show that the level of the Ki-67 expression is statistically significantly related to postoperative survival (p = 0.022), although there are some other studies that have not been able to demonstrate this correlation [30,31].…”

“…Early diagnostics and surgery are the best options to improve patients' survival. However, lack of early specific symptoms and diagnostic markers result in frequent occurrence of widespread tumour invasion and presence of metastases at the time of PDAC diagnostics [4][5][6][7][8]. As surgical treatment is feasible only if distant metastases are absent, major blood vessels are not affected and the patients' general health status is acceptable, only 15-20% patients undergo curative surgical resection [9,10].…”

Role of Neoadjuvant Therapy in the Management of Pancreatic Cancer: Is the Era of Biomarker-Directed Therapy Here?

“…Despite the description of more than 1000 markers that are related to pcc and that could potentially predict clinical outcome, no identified biomarkers are being routinely used in clinical practice 42 . Further studies are warranted to compare neoadjuvant with adjuvant treatment approaches.…”

“…A report on circulating tumour cells as a useful biomarker for staging or for identifying micrometastases at the time of diagnosis and as a tool for management decision-making was presented at the asco 2014 gastrointestinal cancers meeting 41 . Other biomarkers under investigation that might potentially be prognostic include Bax, Bcl-2, Ki-67, pd-ecgf, S100A4, and survivin, among others 37,42 .…”

Can we move towards personalised pancreatic cancer therapy?

“…Numerous prognostic and predictive biomarkers for PDAC have been explored, yet few have been independently validated [8]. Cohort acquisition in non-uniform ways, limited availability of clinical trial material and a lack of focus on biomarker development are major obstacles hampering advances for molecular phenotype-guided therapeutic strategies.…”