Poster Presentation 6th Australian Health and Medical Research Congress 2012

Gene Mutation in Endothelial Pancreato-Biliary Tumours with Particular Reference to K Ras Mutation and DPC4 Inactivation. (#415)

Manju D Chandrasegaram 1 , Daniel Y Chen 1 , Chuan P Tan 1 , Eu L Neo 1 , Paul M Dolan 1 , John W Chen 1 , Mark E Brooke-Smith 1 , Glenice Cheetham 2 , Andrew Ruszkiewicz 3 , Chris S Worthley 1
  1. Hepatobiliary Unit, Royal Adelaide Hospital, Adelaide, SA, Australia
  2. Department of Molecular Pathology, Royal Adelaide Hospital, Adelaide, SA, Australia
  3. Department of Pathology, Royal Adelaide Hospital, Adelaide, SA, Australia

Background: Kras mutation (KRM) is the earliest, most common mutation in pancreatic cancer. Serum KRM has been studied as a potential biomarker for pancreatic cancer. KRM in histologically negative margin tissue is associated with poor prognosis and may have a role in improving pathological staging. Further gene mutation such as DPC4 inactivation (DPC4I) is necessary for cancer progression. Combined KRM and DPC4 status may have value when histology is equivocal.

Aims: To assess KRM and DPC4I in resected pancreatic endothelial tumour and the non-tumourous margin tissue. To evaluate post-operative plasma KRM as a potential screening test for pancreatic neoplasia.

Methods: Pancreaticoduodenectomy patients were recruited from the 2011-2012 database. Tumour and non-tumourous margin tissue was prepared by a single senior pathologist (AR). KRM at codons 12 and 13 were assessed using single nucleotide primer extension assay (SNaPShot TM). DPC4 status was assessed with a monoclonal antibody test (Leica-NCL-DPC).

Results: Fourteen patients were studied: 12 with adenocarcinomas (5 pancreatic; 4 ampullary, 3 biliary) and 2 with benign mucinous tumours (BMT).Six patients (50%) with adenocarcinomas had KRM in their tumour tissue (5 in codon 12 and 1 in codon 13). KRM vs wild type was associated with significantly larger tumours 30 (22-65) mm vs 20 (15-35) mm [median (range)] (p < 0.05 – MW-U). KRM vs wild type tumours had uniform positive nodal status 100% (6/6) vs 33%(2/6) (p<0.061 – Fisher). Non-tumourous margin tissue and plasma KRM was consistently negative in all the patients (p< 0.014 and 0.016 respectively-Fisher).DPC4I occurred in 3 patients, of which 2 were BMT. Patchy DPC4 protein loss occurred in tumour tissue but not adjacent normal tissue.

Conclusions: Plasma KRM was absent in post-pancreaticoduodenectomy patients suggesting little role in the post-operative setting. DPC4I occurred in both BMT consistent with previous reports. KRM was associated with larger malignant tumours,and a trend towards nodal involvement. KRM was absent from non-tumourous margin suggesting a role in margin assessment. 

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