Analysis of Molecular Cytogenetic Alteration of Pancreatic Cancer Identified by Fluorescent In Situ Hybridization (FISH) and its Clinical Significance

형광 동소 보합법을 이용한 췌장암의 세포유전학적 변화에 대한 분석과 그 임상적 의의

Purpose: The purposes of this study are to examine the cytogenetic alterations of pancreatic cancer, by using fluorescent in situ hybridization (FISH), to determine thier correlation with the clinico-pathologic prognostic factors and to identify the cytogenetic factors that can predict the prognosis of pancreatic cancer. Methods: Fresh frozen tissues of pancreatic cancer and normal pancreas that were obtained via pancreatic resection from 20 patients with pancreatic ductal adenocacinoma were analyzed by performing FISH with using locus-specific c-myc, p16, p53 probes and chromosome 18q, 20q probes. We cpmpared the FISH results with the clinico-pathologic prognostic factors. We also examined 16 paraffin-embedded tissues of pancreatic cancer by performing immunohistochemical staining (IHC) with monoclonal antibody to c-myc, p16, p53 and DPC. We then evaluated the correlation between the results of FISH and the results of IHC. Results: At least one alteration of genes or chromosomes was detected in 18 (90.0%) of the 20 pancreatic cancer tissues by FISH, as compared with no alternation in the normal pancreatic tissues: these alteration were an increased copy number of c-myc (66.7%), a decreased copy number of p16 (70.6%), deletion of p53 (100%), loss of chromosome 18q (56.3%) and gain of chromosome 20q (45.0%). IHC demonstrated overexpression of c-myc and p53 in 31.3% and 50.0% of the pancreatic cancer specimens, respectively, and the loss of expressions of p16 and DPC in 25.0% and 93.3% of the pancreatic cancer specimens, respectively. The concordance rate of IHC with FISH was 33.3% to 61.5%. Analysis of the correlation between the cytogenetic changes identified by FISH or IHC and the pathologic prognostic factors showed that only chromosome 20q gain was significantly correlated with the histologic grade (p=0.098) and lymphovascular invasion (p=0.092). However there was no clinical correlation of the cytogenetic changes with respect to recurrence after operation. Conclusion: This study confirms that most pancreatic cancers have cytogenetic alternations, as can be determined by FISH. Especially, the correlation between chromosome 20q gain and the prognostic pathologic factors offers the possibility of a new prognostic biologic marker located in chromosome 20q. However, further studies with more cases are needed to clarify the clinical significance of cytogenetic alternations in pancreatic cancer.