Abstract 1142: Systematic review and meta-analysis of immunohistochemical diagnostic markers for pancreatic ductal adenocarcinoma.
Authors: Ali Asif , Ul-Haq Zia , Mohamed Mohamed , MacKay Daniel Francis , Duthie Fraser , Oien Karin 
Published: August 2014

Background: Pancreatic ductal adenocarcinoma (PDAC) has a five year survival of only 2%. This poor prognosis is partly due to lack of early diagnosis and effective treatment. Surgery is the only curative option but is appropriate for only 10-15% of patients; the remainder have chemotherapy or symptomatic care. Initial diagnosis involves imaging then endoscopy with cytology: diagnosis is important for guiding patient management. The cytological specimens require PDAC to be distinguished from non-neoplastic pancreas. This can be difficult, especially if there is chronic pancreatitis, and because samples are often small. Many immunohistochemical (IHC) biomarkers are differentially expressed between benign and malignant pancreas but none has yet entered routine clinical practice. This study aims to review the evidence on diagnostic biomarkers for PDAC in tissues and cells using IHC. To our knowledge, this is the first meta-analysis on this subject.

Material & Methods: The literature was searched using EMBASE and MEDLINE databases from inception to March 2012. We sought publications which assessed the expression of IHC markers in human PDAC and non-neoplastic pancreas (normal and/or chronic pancreatitis). Specimens included both tissue resected at surgery and cytological samples. We catalogued study characteristics including specimen type, IHC details and biomarkers assessed and their staining results including sensitivity and specificity. In the meta-analysis, for each biomarker, coupled forest plots, bivariate summary estimates and combined summary receiver operating characteristic curves were generated, in turn, then compared and ranked according to pooled sensitivity/specificity.

Results: 2066 papers were initially identified. 59 studies reporting 33 biomarkers were selected for systematic review. From these, 45 studies reporting 16 biomarkers progressed to meta-analysis. Meta-analysis of IHC biomarkers assessed in resection specimens showed 11 differentiating PDAC from non-neoplastic pancreas. The highest ranked biomarkers according to pooled sensitivity/specificity values were: S100P (100% sensitivity/100% specificity); maspin (92%/97%); KOC (85%/98%); and MUC4 (82%/93%). Meta-analysis of cytology specimens showed seven biomarkers differentiating PDAC from non-neoplastic pancreas. The highest ranked were: KOC (85%/100%); SMAD4 (80%/100%); S100P (91%/91%); and mesothelin (64%/92%).

Conclusion: Thirty-three IHC biomarkers for PDAC have been compiled from the literature and the performance of 16 has been quantified and ranked. The highest ranking IHC markers for PDAC were KOC and S100P, then maspin, mesothelin and MUC4. Their reported diagnostic accuracies approach those of optimal conventional cytology. These markers may be worth considering for further clinical validation and potentially routine use in difficult cases.

Citation Format: Asif Ali, Zia Ul-Haq, Mohamed Mohamed, Daniel Francis MacKay, Fraser Duthie, Karin Oien. Systematic review and meta-analysis of immunohistochemical diagnostic markers for pancreatic ductal adenocarcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1142. doi:10.1158/1538-7445.AM2013-1142