APCpromoter is frequently methylated in pancreatic juice of patients with pancreatic carcinomas or periampullary tumors.
Early detection of pancreatic and periampullary neoplasms is critical to improve their clinical outcome. The present authors previously demonstrated that DNA hypermethylation ofadenomatous polyposis coli (APC), histamine receptor H2 (HRH2), cadherin 13 (CDH13), secreted protein acidic and cysteine rich (SPARC)andengrailed-1 (EN-1)promoters is frequently detected in pancreatic tumor cells. The aim of the present study was to assess their prevalence in pancreatic juice of carcinomas of the pancreas and periampullary area. A total of 135 pancreatic juices obtained from 85 pancreatic cancer (PC), 26 ampullary carcinoma (AC), 10 intraductal papillary mucinous neoplasm (IPMN) and 14 chronic pancreatitis (CP) patients were analyzed. The methylation status of theAPC, HRH2, CDH13, SPARCandEN-1promoters was analyzed using methylation specific-melting curve analysis (MS-MCA).Kirsten rat sarcoma viral oncogene homolog (KRAS)mutations were also tested with allele-specific quantitative polymerase chain reaction amplification. Out of the 5 promoters analyzed,APC(71%) andHRH2(65%) were the most frequently methylated in PC juice.APCmethylation was also detected at a high frequency in AC (76%) and IPMN (80%), but only occasionally observed in CP (7%).APCmethylation had a high sensitivity (71-80%) for all types of cancer analyzed. The panel (where a sample scored as positive when ≥2 markers were methylated) did not outperformAPCas a single marker. Finally,KRASdetection in pancreatic juice offered a lower sensitivity (50%) and specificity (71%) for detection of any cancer.APChypermethylation in pancreatic juice, as assessed by MS-MCA, is a frequent event of potential clinical usefulness in the diagnosis of pancreatic and periampullary neoplasms.
Translational Research Laboratory, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute, Duran i Reynals Hospital, 08907 Barcelona, Spain.
Mireia M
MM
Ginesta
Translational Research Laboratory, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute, Duran i Reynals Hospital, 08907 Barcelona, Spain.
Zamira Vanessa
ZV
Diaz-Riascos
Department of General and Digestive Surgery, Bellvitge University Hospital, 08907 Barcelona, Spain.
Juli
J
Busquets
Department of General and Digestive Surgery, Bellvitge University Hospital, 08907 Barcelona, Spain.
Núria
N
Pelaez
Department of Pathology, Bellvitge University Hospital, 08907 Barcelona, Spain.
Teresa
T
Serrano
Department of Mechanism of Tumor Progression, Institute of Predictive and Personalized Cancer Medicine, 08916 Barcelona, Spain.
Miquel Àngel
MÀ
Peinado
Department of Surgery, Joan XXIII Hospital, 43005 Tarragona, Spain.
Rosa
R
Jorba
Department of Surgery, Hepatopancreatic Unit, Parc Taulí University Hospital, 08208 Barcelona, Spain.
Francisco Javier
FJ
García-Borobia
Translational Research Laboratory, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute, Duran i Reynals Hospital, 08907 Barcelona, Spain.
Gabriel
G
Capella
Department of General and Digestive Surgery, Bellvitge University Hospital, 08907 Barcelona, Spain.
Joan
J
Fabregat
AC; APC; IPMN; PC; cancer genetics; methylation; molecular pathology; oncology; pancreatic cancer