Detection of Chromosomal Abnormalities by Fluorescence In Situ Hybridization on Ultrasound Guided Fine-Needle Aspiration Samples from Pancreas
Yaxia Zhang, Monica Garcia-Buitrago, Parvin Ganjei, Yao-Shan Fan, Afonso Ribeiro. University of Miami, Miller School of Medicine-Jackson Memorial Hospital, Miami, FL; University of Miami, Miller School of Medicine-UMHC/Sylvester, Miami, FL
Background: Diagnosis of pancreatic malignancy is frequently established on cytological specimens acquired by endoscopic ultrasound guided fine-needle aspiration (EUS-FNA). However, the sensitivity of cytology depends on several factors such as: tumor characteristics, experience of cytopathologists, and endosonographer. Previous studies have demonstrated genetic alterations in pancreatic carcinoma including mutations in oncogenes such as KRAS, chromosomal instability and inactivation of tumor suppressor genes such as p16 on 9p. The aim of this study is to verify the significance of cytogenetic abnormalities by fluorescence In situ hybridization (FISH) in EUS-FNA from patients with pancreatic mass.
Design: EUS-FNA procedures were performed on 81 patients who presented with pancreatic mass between January 2009 and March 2011. Samples were submitted for cytology and cytogenetic studies using the commercially available UroVysion kit. FISH detects aneuploidy for chromosomes 3, 7, 17 and loss of p16 gene at 9p21. Malignancy by FISH is defined by more than 20% cells with 2 or more chromosomes with extra-copies or deletion of 9p21 in more than 20% cells. The final diagnosis was made on clinical follow-up, cytology, and histological samples.
Results: Out of 81 patients, 12 showed benign conditions (chronic pancreatitis, autoimmune pancreatitis), 1 solid and cystic pseudopapillary tumor, 5 neuroendocrine tumors, 7 intraductal papillary mucinous neoplasms, 1 metastatic renal cell carcinoma, 1 mucinous cystadenoma, and 54 adenocarcinomas. In 47 out of 54 (87%) adenocarcinomas, cytogenetic abnormalities were detected by FISH. Loss of p16 was observed in 81% (38/47) of cases as heterozygous deletion (43%, 20/47) or homozygous deletion (38%, 18/47). Loss of P16 was not seen on IPMN-related or endocrine carcinomas. The second most common abnormality was gain of chromosome 3, 7 and 17. FISH detected 13 additional cases of pancreatic adenocarcinoma missed by cytology. All (12) benign conditions were negative by FISH.
Conclusions: Loss of tumor suppressor gene P16 and chromosomal instability are frequent events in the pancreatic ductal adenocarcinoma. FISH analysis on EUS-FNA specimens is a useful and specific diagnostic tool to detect adenocarcinoma.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 58, Tuesday Morning