Fluorescence in situ hybridization to visualize genetic abnormalities in interphase cells of acinar cell carcinoma, ductal adenocarcinoma, and islet cell carcinoma of the pancreas

Abstract

Objective: To use fluorescence in situ hybridization (FISH) to visualize genetic abnormalities in interphase cell nuclei (interphase FISH) of acinar cell carcinoma, ductal adenocarcinoma, and islet cell carcinoma of the pancreas.

Patients and methods: Between April 4, 2007, and December 4, 2008, interphase FISH was used to study paraffin-embedded preparations of tissue obtained from 18 patients listed in the Mayo Clinic Biospecimen Resource for Pancreas Research with a confirmed diagnosis of acinar cell carcinoma, ductal adenocarcinoma, islet cell carcinoma, or pancreas without evidence of neoplasia. FISH probes were used for chromosome loci of APC (see glossary at end of article for expansion of all gene symbols), BRCA2, CTNNB1, EGFR, ERBB2, CDKN2A, TP53, TYMP, and TYMS. These FISH probes were used with control probes to distinguish among various kinds of chromosome abnormalities of number and structure.

Results: FISH abnormalities were observed in 12 (80%) of 15 patients with pancreatic cancer: 5 of 5 patients with acinar cell carcinoma, 5 of 5 patients with ductal adenocarcinoma, and 2 (40%) of 5 patients with islet cell carcinoma. All 3 specimens of pancreatic tissue without neoplasia had normal FISH results. Gains of CTNNB1 due to trisomy 3 occurred in each tumor with acinar cell carcinoma but in none of the other tumors in this study. FISH abnormalities of all other cancer genes studied were observed in all forms of pancreatic tumors in this investigation.

Conclusion: FISH abnormalities of CTNNB1 due to trisomy 3 were observed only in acinar cell carcinoma. FISH abnormalities of genes implicated in familial cancer, tumor progression, and the 5-fluorouracil pathway were common but were not associated with specific types of pancreatic cancer.

FIGURE 1.

Illustration of the chromosomal loci for each of the cancer-control sets of fluorescence-labeled DNA and in situ hybridization probes used in this study. For expansion of gene symbols, see glossary at end of article.

FIGURE 2.

Representative microphotographic images (×1000) of normal and abnormal cell nuclei from paraffin-embedded pancreatic cancer specimens processed by fluorescence in situ hybridization (FISH). A, Patient 9 with pancreatitis showing normal FISH results for BRCA2 (orange) and LAMP1 (green). B, Patient 14 with islet cell carcinoma showing 3 FISH signals for APC (green) and EGR1 (orange) as part of a near-tetraploid condition. C, Patient 3 with acinar cell carcinoma showing amplification (≥15 target signals) of EGFR (orange) and cen 7 (green). D, Patient 5 with ductal cell adenocarcinoma showing 1 TP53 (orange) and 2 ERBB2 (green) signals, suggesting a deletion or unbalanced translocation.