APC promoter is frequently methylated in pancreatic juice of patients with pancreatic carcinomas or periampullary tumors

Abstract

Abstract. Early detection of pancreatic and periampullary neoplasms is critical to improve their clinical outcome. The present authors previously demonstrated that DNA hypermethylation of adenomatous polyposis coli (APC), histamine receptor H2 (HRH2), cadherin 13 (CDH13), secreted protein acidic and cysteine rich (SPARC) and engrailed-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 the APC, HRH2, CDH13, SPARC and EN-1 promoters 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%) and HRH2 (65%) were the most frequently methylated in PC juice. APC methylation was also detected at a high frequency in AC (76%) and IPMN (80%), but only occasionally observed in CP (7%). APC methylation 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 outperform APC as a single marker. Finally, KRAS detection in pancreatic juice offered a lower sensitivity (50%) and specificity (71%) for detection of any cancer. APC hypermethylation in pancreatic juice, as assessed by MS-MCA, is a frequent event of potential clinical usefulness in the diagnosis of pancreatic and periampullary neoplasms.

Early screening and diagnosis strategies of pancreatic cancer: a comprehensive review

“…Genetic analysis of pancreatic juice of the patients with pancreatic cancer was able to detect mutant DNA, such as Kras , TP53 , and SMAD4 , for the discrimination of pancreatic cancer from the healthy controls or pre‐cancerous lesions [ 105 , 106 ]. Additionally, promoters of adenomatous polyposis coli ( APC ) and histamine receptor H2 ( HRH2 ) genes were found to be frequently methylated in pancreatic cancer juice, serving as potential diagnostic biomarkers [ 107 ]. Through the detection of exosome‐derived miRNAs from pancreatic juice, Japanese researchers found that miR‐21 and miR‐155 levels could discriminate PDAC patients from chronic pancreatitis patients with an AUC of 0.90 and 0.89, respectively, and that a combination with cytology displayed even higher accuracy [ 108 ].…”

The Diagnostic Accuracy of Mutant KRAS Detection from Pancreatic Secretions for the Diagnosis of Pancreatic Cancer: A Meta-Analysis

“…Importantly, the study demonstrating the lowest sensitivity utilised DNA sequencing technology to detect KRAS mutation [ 42 ] and it is well recognised that this technique has a lower sensitivity than methods such as RFLP [ 47 ]. A second study demonstrating low sensitivity was that of Trumper et al [ 42 ]; one of the few prospective studies identified.…”

Epigenetic inactivation of tumour suppressor coding and non-coding genes in human cancer: an update

“…It is important to mention that some Wnt ligands cannot activate b-Catenin, and so act as Wnt/b-Catenin antagonists, examples of which include WNT5a and WNT7a, both of which are commonly silenced in CRC, pancreatic and lung cancer [55,56]. APC is frequently mutated in CRC, but it is also inactivated by promoter hypermethylation in colon, breast and pancreatic cancer [57][58][59]. NKD2, DACT2 and CXXC4 inhibit DSH.…”