K-ras, p53, and DPC4 (MAD4) alterations in fine-needle aspirates of the pancreas: A molecular panel correlates with and supplements cytologic diagnosis

• Published in: American journal of clinical pathology 2002-05, Vol.117 (5), p.755-765
• Main Authors: VAN HEEK, Tjarda, RADER, Anne E, OFFERHAUS, G. Johan A, MCCARTHY, Denis M, GOGGINS, Michael, HRUBAN, Ralph H, WILENTZ, Robb E
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Aged; Biological and medical sciences; Biomarkers, Tumor - metabolism; Biopsy, Needle; Dissection; DNA, Neoplasm - analysis; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Female; Fluorescent Antibody Technique, Indirect; Gastroenterology. Liver. Pancreas. Abdomen; Genetic Markers; Humans; Immunohistochemistry; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Micromanipulation - methods; Oncogene Protein p21(ras) - genetics; Oncogene Protein p21(ras) - metabolism; Pancreas - metabolism; Pancreas - pathology; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Polymerase Chain Reaction; Reproducibility of Results; Sensitivity and Specificity; Single-Blind Method; Smad4 Protein; Trans-Activators - genetics; Trans-Activators - metabolism; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Tumors
• ISSN: 0002-9173; 1943-7722
• DOI: 10.1309/5RQ0-JCQU-5XF2-51LQ

Between January 1997 and February 2000, 101 fine-needle pancreatic aspirates were obtained. After a cytologic diagnosis was made, possible molecular alterations were determined on the 94 aspirates with adequate tissue using a molecular panel (K-ras, p53, and DPC4 [MAD4] genes). The 94 aspirates were categorized as follows: diagnostic of adenocarcinoma, 48 (51%); atypical (suggestive of but not diagnostic of adenocarcinoma), 19 (20%); negative for adenocarcinoma, 25 (2 7%); diagnostic of a neoplasm other than adenocarcinoma, 2 (2%). Clinical follow-up revealed that 3 patients (12%) with negative cytologic diagnoses and 12 patients (63%) with atypical cytologic diagnoses had adenocarcinoma. Of 63 with a final diagnosis of adenocarcinoma, 42 (67%) had an alteration in at least 1 of the genes analyzed. In contrast, only 2 (6%) of 31 patients without adenocarcinoma had an alteration in 1 gene on the panel. Overall, the molecular analyses supported the diagnosis of adenocarcinoma in 6 (32%) of 19 aspirates originally diagnosed as atypical by cytology alone. A molecular panel that includes the K-ras, p53, and DPC4 (MAD4) genes correlates with and can supplement traditional cytologic diagnosis of pancreatic fine-needle aspirates.