To augment cytological diagnosis of pancreatic ductal adenocarcinoma (PDAC) in tissue samples obtained by minimally invasive endoscopic ultrasound-guided fine needle aspiration, we investigated whether a small set of molecular markers could accurately distinguish PDAC from chronic pancreatitis (CP). Expression levels of 29 genes were first determined by quantitative real-time RT-PCR in a training set of tissues in which the final diagnosis was PDAC (n 5 20) or CP (n 5 10). Using receiver operator characteristic curve analysis, we determined that the single gene with the highest diagnostic accuracy for discrimination of CP vs. PDAC in the training study was urokinase plasminogen activator receptor (UPAR; AUC value 5 0.895, 95% CI 5 0.728-0.976). In the set of test tissues (n 5 14), the accuracy of UPAR decreased to 79%. However, we observed that the addition of 6 genes (EPCAM2, MAL2, CEA5, CEA6, MSLN and TRIM29; referred to as the 6-gene classifier) to UPAR resulted in high accuracy in both training and testing sets. Excluding 3 samples (out of 44; 7%) for which results of the UPAR/6-gene classifier were ''undefined,'' the accuracy of the UPAR/6-gene classifier was 100% in training samples (n 5 29), 92% in 12 test samples (p 5 0.004 that results were randomly generated; p 5 0.046 that the UPAR/6-gene classifier was comparable to UPAR alone; v 2 test), 100% in 3 samples for which the initial cytological diagnosis was ''suspicious'' and 98% (40/41) overall. Our results provide evidence that molecular marker expression data can be used to augment cytological analysis. ' 2006 Wiley-Liss, Inc.Key words: chronic pancreatitis; pancreatic ductal adenocarcinoma; urokinase plasminogen activator receptor; diagnostic accuracy Although the incidence of pancreatic ductal adenocarcinoma (PDAC) is only 1-2% and relatively low compared to other cancers, nearly all patients die from PDAC within 1-2 years.
We report major responses in 4 of 4 patients with hairy cell leukemia (HCL) who have recently been treated on a phase I trial with the recombinant immunotoxin LMB-2. The immunotoxin, designed to target CD25+ malignancies, is composed of the Fv portion of the anti-Tac (anti-CD25) antibody, fused to a 38-kD truncated form of Pseudomonas exotoxin A, and has previously been called anti-Tac(Fv)-PE38. All 4 HCL patients were resistant to standard and salvage therapies for HCL, including 2-chlorodeoxyadenosine (CdA) and interferon , and all patients responded to LMB-2 after a single cycle. One patient treated with 2 cycles had a complete remission (CR), with regression of HCL cells from the blood and marrow and resolution of splenomegaly and pancytopenia. As is typical for patients in CR after treatment with CdA, minimal residual disease was detectable by flow cytometry of the bone marrow aspirate. This patient has not relapsed after 11 months. Three other patients had 98% to 99.8% reductions in malignant circulating cells. These results represent a proof of principal that targeted therapy with recombinant Fv-containing proteins can be clinically useful. LMB-2 may be an effective new therapy for patients with chemotherapy-resistant CD25+HCL.
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