title: KRAS mutational analysis in ductal adenocarcinoma of the pancreas and its clinical significance.
abstract: Mutations of KRAS are detectable in 70-90% of pancreatic duct adenocarcinomas (PDAC), using direct sequencing. We used a highly sensitive molecular method in order to investigate: (a) the frequency and prognostic significance of different KRAS mutations and, (b) whether the presence of KRAS mutations in histologically-negative resection margins of PDAC could explain local tumor recurrence after surgery. Twenty-seven patients with histologic diagnosis of PDAC, radical pancreaticoduodenectomy and histologically-negative margins were evaluated. KRAS mutations were searched for mutant-enriched PCR in tumor and negative resection margins. KRAS mutations were detected in 85.2% of the cases; the most frequent mutation was G12D (48.1%). Shorter OS was found in patients with G12D (25 months; 95% CI, 20.5-29.5), vs patients with other mutations (31.5 months; 95% CI, 25.6-37.1) (N.S.). KRAS mutation in histologically-negative margins was detected in one patient who died of locoregional recurrence; six patients had tumor recurrence but no mutations in surgical margins. The high frequency of KRAS mutations suggests a search for KRAS status to improve the diagnosis in suspected cases; the G12D mutation could be related to poor prognosis, but without statistical significance. No correlation was found between the frequency of cancer recurrence and KRAS mutations in surgical margins.
authors.affiliation: Department of Health Sciences, Division of Pathology, University of Eastern Piedmont "Amedeo Avogadro", Via Solaroli 17, 28100 Novara, Italy. Electronic address: miglio@med.unipmn.it.
authors.forename: Umberto
authors.initials: U
authors.lastname: Miglio
authors.affiliation: Department of Translational Medicine, Division of Surgery, University of Eastern Piedmont "Amedeo Avogadro", Via Solaroli 17, 28100 Novara, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Oldani
authors.affiliation: Department of Health Sciences, Division of Pathology, University of Eastern Piedmont "Amedeo Avogadro", Via Solaroli 17, 28100 Novara, Italy; Division of Cancer Genomics, "Edo ed Elvia Tempia Valenta" Foundation, Via Malta 2, 13900 Biella, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Mezzapelle
authors.affiliation: Division of Pathology, "Maggiore della Carità" Hospital, C.so Mazzini 18, 28100 Novara, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Veggiani
authors.affiliation: Division of Pathology, "Maggiore della Carità" Hospital, C.so Mazzini 18, 28100 Novara, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Paganotti
authors.affiliation: Department of Translational Medicine, Division of Surgery, University of Eastern Piedmont "Amedeo Avogadro", Via Solaroli 17, 28100 Novara, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Garavoglia
authors.affiliation: Department of Health Sciences, Division of Pathology, University of Eastern Piedmont "Amedeo Avogadro", Via Solaroli 17, 28100 Novara, Italy; Division of Pathology, "Maggiore della Carità" Hospital, C.so Mazzini 18, 28100 Novara, Italy.
authors.forename: Renzo
authors.initials: R
authors.lastname: Boldorini
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000401:mortality; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000401:mortality; D010179:Pancreas / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000401:mortality; D011379:Prognosis
keywords: Adenocarcinoma; KRAS mutations; Pancreas