Am J Surg Pathol. maspin was 84.8%, 81.8%, and 87.5%, respectively. Specificity of these three markers was 100%. Sensitivity and specificity of pVHL for detecting nontumoral pancreatic tissue were 100% and 81.8%, respectively. When maspin, IMP3, and S100P expression were used together as triple test, sensitivity was 62.5% and specificity 100%. However, when any two of each three markers were evaluated (triple test/dual response), sensitivity reached 93.8% and specificity 100%. Conclusion: We observed that dual response in triple test (positive staining with two of these three markers) of maspin, IMP3, and S100P immunocytochemistry is very sensitive and specific in differential diagnosis of PDA and non-neoplastic pancreatic lesions. pVHL may have an additional role, when triple assessment is not satisfactory. 0.01). When 2+, 3+, and 4+ staining were considered as positive staining, sensitivity and specificity of c-Raf IMP3, S100P, and maspin were high enough to detect PDAC (sensitivity 81.8%, 84.8%, 87.5% and specificity was 100% for all three markers). pVHL was observed to be very sensitive (100%) for detecting non-neoplastic pancreatic tissue. Some of the PDAC cases (13/39) were stained with pVHL (mostly focal and weak). Specificity of this marker for non-neoplastic pancreatic tissue was 81.8% [Table 4]. Table 4 Sensitivity, specificity, accuracy, and positive and negative Lu AE58054 (Idalopirdine) predictive values for IMP3, S100P, maspin, and pVHL Open in a separate window Test performance of possible antibody combinations was also evaluated. When maspin, IMP3, and S100P expression were used together as triple test, sensitivity was 62.5% and specificity 100%. However, when any two of each three markers were evaluated (triple test/dual response), sensitivity reached 93.8% and specificity 100%. DISCUSSION Recently, many biomarkers were investigated to decrease interobserver variability of interpretation of morphological assessment of pancreatic lesions. In this study, we arbitrarily categorized maspin, IMP3, and S100P as triple test. The results of this study demonstrate that dual response in triple test of maspin, IMP3, and S100P immunocytochemistry is sufficient to differentiate PDAC from benign mimickers. However, when triple assessment is not satisfactory, use of pVHL might be valuable. PDAC is the fourth leading cause of cancer-related death worldwide.[14] In majority of the cases, PDAC is not curable by surgery and diagnosis has been made with FNAB or core needle biopsies.[2] Differentiation of PDAC from non-neoplastic pancreatic tissue in cytopathological assessment is not always straightforward. There are several reports that evaluate diagnostic value of cytological criteria in PDAC.[15,16] Despite these well-defined cytological criteria, false-negative rates, atypical, and suspicious diagnosis remain still high, especially when a PDAC was evaluated by a less experienced pathologists. To overcome this problem, several antibodies have been evaluated. There are several reports that interpret diagnostic value of S100P, maspin, pVHL, and IMP3 in the differential diagnosis of PDAC from normal/reactive pancreatic tissue. Studies that evaluate these antibodies in FNAB smears or cell blocks are limited to few.[3,7,8,9] IMP3 is an oncofetal protein that belongs to insulin-like growth factor II mRNA binding protein Lu AE58054 (Idalopirdine) (IMP). In adult tissues, IMP3 is expressed at low or undetectable levels[17,18] but in malignant tumors is over-expressed in stomach, colon, pancreas, lung, renal cell, and liver cancers.[18,19,20,21,22] Zhao em et al /em . applied KOC (IMP3) to 48 alcohol-fixed, PAP-stained EUS-FNAB smears (40 PDAC and 8 benign cases) and Lu AE58054 (Idalopirdine) reported KOC expression as 88% in PDAC and none of the benign cases.[7] Even though the size of their study is limited, it gives very important information that IMP3 can be evaluated on alcohol-fixed FNA smears. S100P belongs to S100 family of calcium-binding protein and has been found to demonstrate increased level of expression during progression from pancreatic intraepithelial neoplasia to invasive adenocarcinoma.[23] To our best knowledge, the first study that evaluated diagnostic value of S100P in FNAB specimens of the pancreas was published in 2008.[8] They found positive staining with S100P antibody in all cases of PDAC and atypical or suspicious cases. Cases that were diagnosed as atypical or Lu AE58054 (Idalopirdine) suspicious proved to be PDAC in surgical material. Dim em et al /em . studied five markers including S100P, prostate stem cell antigen, fascin, 14-3-3 sigma, and mesothelin in endoscopic ultrasound-guided FNAB of the pancreas to evaluate usefulness of these antibodies in differential diagnosis of PDAC and normal pancreatic tissue.[9] They reported S100P as the best diagnostic marker among five others, which represented 90% of sensitivity and 67% of specificity.[9] In this study, when maspin, IMP3, and S100P expression were present, it was strongly evident.