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Our objective was to explore alteration of the epidermal growth factor receptor signaling pathway in ampullary carcinoma. Immunohistochemical studies were employed to evaluate expression of amphiregulin as well as expression and activation of epidermal growth factor receptor. A lab developed assay was used to identify mutations in the epidermal growth factor receptor pathway genes, including KRAS, BRAF, PIK3CA, PTEN and AKT1. Fifty two ampullary carcinomas were identified, including 25 intestinal-type and 24 pancreatobiliary-type tumors with the intestinal type being associated with a younger age at diagnosis (p=0.03) and a better prognosis (p

Background Pathologic evaluation may lack the sensitivity required for accurate staging of the axilla in breast cancer patients. We have completed enrollment of a multi-institutional prospective cohort study designed to determine if molecular analyses can improve axillary staging. In subset analyses, we have attempted to address the following questions: (1) Does molecular analysis improve the sensitivity of sentinel lymph node biopsy (SLNB) and (2) is the sentinel lymph node (SLN) hypothesis valid at the molecular level? Methods Four hundred eighty-nine subjects with T1, T2, or T3 breast cancer and no evidence of axillary lymph node (ALN) involvement were enrolled. ALNs were analyzed by routine pathology (hematoxylin-eosin staining), and by multimarker real-time reverse transcriptase-polymerase chain reaction analysis CRT-PCR to detect breast cancer metastases. Pathology and molecular data for both SLNs and nonsentinel ALNs were available for a subset of 207 subjects. Results The sensitivity of pathologic analysis of the SLN to predict the pathologic status of ALNs was 84.1%. The sensitivity of combining pathologic with molecular analysis of the SLN to predict the pathologic status of ALNs was 92.8%, a statistically significant increase in sensitivity (P = .031 by the McNemar test for correlated proportions). Finally, the sensitivity of combining pathologic with molecular analysis of the SLN to predict the pathologic or molecular status of ALNs was 85.4%. Conclusions The combination of pathologic and molecular analysis of SLNs resulted in the highest sensitivity for prediction of the pathologic status of ALNs. The data also provide evidence that the SLN hypothesis remains valid at the molecular level.

The clinical management of non-small cell lung cancer (NSCLC) would benefit greatly by a test that was able to detect small amounts of NSCLC in the peripheral blood. In this report, we used a novel strategy to enrich tumor cells from the peripheral blood of 24 stage I to IV NSCLC patients and determined expression levels for six cancer-associated genes (lunx, muc1, KS1/4, CEA, CK19, and PSE). Using thresholds established at three standard deviations above the mean observed in 15 normal controls, we observed that lunx (10 of 24, 42%), muc1 (5 of 24, 21%), and CK19 (5 of 24, 21%) were overexpressed in 14 of 24 (58%) peripheral blood samples obtained from NSCLC patients. Patients who overexpressed either KS1/4 (n = 2) or PSE (n = 1) also overexpressed either lunx or muc1. Of patients with presumed curable and resectable stage I to II disease (n = 7), at least one marker was overexpressed in three (43%) patients. In advanced stage III to IV patients (n = 17), at least one marker was overexpressed in 11 patients (65%). These results provide evidence that circulating tumor cells can be detected in NSCLC patients by a high throughput molecular technique. Further studies are needed to determine the clinical relevance of gene overexpression.

Identification of Molecular Markers That Discriminate Between Pancreatic Ductal Adenocarcinoma and Chronic Focal Pancreatitis Using Endoscopic Ultrasound Fine Needle Aspiration and Real-Time RT-PCR David H. Robbins, Yian Chen, Kaidi Mikhitarian, Carlton Barnett, David Cole, William Gillanders, Mike Mitas, Brenda Hoffman Chronic pancreatitis (CP) is an incapacitating disease marked by progressive destruction and replacement of the pancreatic parenchyma with fibrous tissue. At some point in the progression of this disease, chronic pancreatitis may present as a discrete mass, typically of the pancreatic head, and this clinical entity, chronic focal pancreatitis (CFP), is often indistinguishable from malignant disease. Since the clinical, radiographic, endosonographic, gross, and histopathologic features of CFP and pancreatic ductal adenocarcinoma cancer (PDAC) are very similar, reliably distinguishing between them without surgical exploration is a challenging diagnostic dilemma. The recent identification of genes overexpressed in PDAC and chronic pancreatitis by gene profiling provides the opportunity to more precisely characterize suspicious lesions using molecular markers. To determine whether a panel of molecular markers could accurately discriminate PDAC from CFP, we measured gene expression levels from tissue specimens obtained during endoscopic ultrasound-fine needle aspiration (EUS-FNA) examination using quantitative real-time RT-PCR. Gene expression levels of 14 candidate markers were determined in 20 EUS-FNA samples from patients with PDAC, and 10 EUS-FNA samples from patients with known CP and presumed CFP. Comparing gene expression levels between these two groups, we observed that seven genes (mesothelin, MUC4, CEA, SHH, S100P, FXYD3, and TRIM29) were significantly overexpressed in PDAC compared to CFP (p ! 0.05, two sample t test). Receiver operator characteristic curve analysis showed that the diagnostic accuracy for these seven markers was above 75%. These results suggest that one or more of these seven molecular markers improves the discriminatory power of EUS-FNA to distinguish benign from malignant pancreatic disease. W1279 CEAtTo Amylase Ratio for the Diagnosis of Malignant and Premalignant Cystic Lesions of the Pancreas Michael K. Sanders, Raquel E. Davila, Douglas O. Faigel Introduction: The differentiation of pancreatic cystic lesions between those with significant malignant potential (mucinous cystadenomas, cystadenocarcinomas) from cysts without this potential (serous cystadenomas, pseudocysts) is challenging. EUS-FNA cytology may be non-diagnostic and tumor markers have imperfect sensitivity and specificity. Both cyst fluid CEA and amylase have been advocated as useful markers. Aim: To determine if the ratio of CEA to amylase improves diagnostic accuracy over either marker alone. Methods: A retrospective chart review was performed of all cases of pancreatic cysts evaluated by EUS-FNA from October 2001 to September 2004. The final histology of the cysts was determined by surgical pathology or clinical follow-up with radiographic imaging. Those in whom CEA (ng/ml) and amylase (U/L) levels were measured were included in the study. EUS-FNA was done using the Pentax FG-36UX echoendoscope and WilsonCook 22 gauge needle. Sensitivity and specificity were calculated for each marker and also for the ratio CEA/ln(Amylase). Cut off values were determined by ROC analysis. Results: 25 patients (12M, 13F) had EUS-FNA of pancreatic cysts and final histology determined by surgery and clinical follow-up. 18 patients had both CEA and amylase levels and formed the study cohort. There were 9 males and 9 females, mean age 57yrs (range 28-83). Five had neoplastic cysts (1 cancer, 4 mucinous) determined by surgical pathology, and 13 had benign cysts (11 pseudocysts, 2 serous). 6 of the 13 benign cysts were confirmed surgically and 7 showed resolution on repeat imaging at 6-24 months consistent with benign pseudocysts. See Table. Conclusions: CEAO150 ng/ml was the single best predictor for malignant and premalignant cystic pancreatic lesions. The CEA/ln(Amylase) ratio O 40 may improve specificity without loss of sensitivity.