BACKGROUND: The objective of this study was to identify genomic alterations in resectable pancreatic cancer (PCA). Chromosomal imbalances were correlated with histopathological and clinical data to verify their prognostic significance. METHODS: Specimens of 33 PCA were investigated by comparative genomic hybridization. Microdissection was used for separation of PCA from the normal cells before isolation of DNA; nick-end labeling and hybridization were performed according to standard protocols. Aberrations were correlated with staging and grading using log-rank test and Cox regression. Survival rates were plotted using the Kaplan-Meier method. RESULTS: Twenty-eight (85%) PCA showed aberrations. Gains of chromosomal material were most frequently identified on 8q (42%), 13q (30%), 18p (21%), and 3q (18%). Genetic losses were frequently detected on 1p (45%), 22 (42%), 19 (36%), 17p (27%), 18q and 8p (15% each), and 3p (12%). Losses of 8p (n = 5) and 3p (n = 4) were only detected in stages III and IV (P < 0.05). Median survival time of all patients was 13 months. Median survival time of patients with aberration of 8q (n = 14) was 8.5 months compared to 16 months in patients without gain of 8q (n = 19; P = 0.029). CONCLUSIONS: The chromosomal regions containing genetic alterations represent potential loci for new target genes in PCA. The significant correlation of gain of chromosome 8q with short survival time suggests that 8q may be a new marker to assess prognosis and malignant potential of resected PCA in the individual patient, thereby helping to identify patients at risk for recurrence that might profit from adjuvant therapy.
BACKGROUND: The objective of this study was to identify genomic alterations in resectable pancreatic cancer (PCA). Chromosomal imbalances were correlated with histopathological and clinical data to verify their prognostic significance. METHODS: Specimens of 33 PCA were investigated by comparative genomic hybridization. Microdissection was used for separation of PCA from the normal cells before isolation of DNA; nick-end labeling and hybridization were performed according to standard protocols. Aberrations were correlated with staging and grading using log-rank test and Cox regression. Survival rates were plotted using the Kaplan-Meier method. RESULTS: Twenty-eight (85%) PCA showed aberrations. Gains of chromosomal material were most frequently identified on 8q (42%), 13q (30%), 18p (21%), and 3q (18%). Genetic losses were frequently detected on 1p (45%), 22 (42%), 19 (36%), 17p (27%), 18q and 8p (15% each), and 3p (12%). Losses of 8p (n = 5) and 3p (n = 4) were only detected in stages III and IV (P < 0.05). Median survival time of all patients was 13 months. Median survival time of patients with aberration of 8q (n = 14) was 8.5 months compared to 16 months in patients without gain of 8q (n = 19; P = 0.029). CONCLUSIONS: The chromosomal regions containing genetic alterations represent potential loci for new target genes in PCA. The significant correlation of gain of chromosome 8q with short survival time suggests that 8q may be a new marker to assess prognosis and malignant potential of resected PCA in the individual patient, thereby helping to identify patients at risk for recurrence that might profit from adjuvant therapy.
Authors: Wilson Petrushnko; Justin S Gundara; Philip R De Reuver; Greg O'Grady; Jaswinder S Samra; Anubhav Mittal Journal: HPB (Oxford) Date: 2016-07-14 Impact factor: 3.647