Diagnosis of pancreatic neoplasms using a novel method of DNA methylation analysis of mucin expression in pancreatic juice.
Mucins (MUC) play crucial roles in carcinogenesis and tumor invasion in pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasms (IPMNs). Our immunohistochemistry (IHC) studies have shown a consensus position on mucin expression profiles in pancreatic neoplasms as follows: MUC1-positive but MUC2-negative expression in PDACs; MUC1-negative but MUC2-positive expression in intestinal-type IPMNs (dangerous type); MUC1-negative and MUC2-negative expression in gastric-type IPMNs (safe type); High MUC4 expression in PDAC patients with a poor outcome; and MUC4-positive expression in intestinal-type IPMNs. We also showed that three mucin genes (MUC1, MUC2 and MUC4) expression in cancer cell line was regulated by DNA methylation. We have developed a novel 'methylation-specific electrophoresis (MSE)' method to analyze the DNA methylation status of mucin genes by high sensitivity and resolution. By using the MSE method, we evaluated pancreatic juice samples from 45 patients with various pancreatic lesions. The results were compared with final diagnosis of the pancreatic lesions including IHC of mucin expression in the paired pancreatic tissues. The results indicated that the DNA methylation status of MUC1, MUC2 and MUC4 in pancreatic juice matched with the mucin expression in tissue. Analyses of the DNA methylation status of MUC1, MUC2 and MUC4 were useful for differential diagnosis of human pancreatic neoplasms, with specificity and sensitivity of 87% and 80% for PDAC; 100% and 88% for intestinal-type IPMN; and 88% and 77% for gastric-type IPMN, respectively. In conclusion, MSE analysis of human pancreatic juice may provide useful information for selection of treatment for pancreatic neoplasms.
Department of Human Pathology, Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Kagoshima, Japan.
Seiya
S
Yokoyama
Department of Human Pathology, Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Kagoshima, Japan.
Sho
S
Kitamoto
Department of Human Pathology, Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Kagoshima, Japan.
Michiyo
M
Higashi
Department of Human Pathology, Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Kagoshima, Japan.
Yuko
Y
Goto
Division of Endoscopy, Chiba Cancer Center, Chiba, Chiba, Japan.
Taro
T
Hara
Division of Surgical Pathology, Chiba Cancer Center, Chiba, Chiba, Japan.
Dai
D
Ikebe
Division of Gastroenterology, Chiba Cancer Center, Chiba, Chiba, Japan.
Taketo
T
Yamaguchi
Department of Gastroenterology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
Yoshifumi
Y
Arisaka
Division of Gastroenterology, Nanpuh Hospital, Kagoshima, Kagoshima, Japan.
Toru
T
Niihara
Division of Gastroenterology, Nanpuh Hospital, Kagoshima, Kagoshima, Japan.
Hiroto
H
Nishimata
Division of Surgical Pathology, Nanpuh Hospital, Kagoshima, Kagoshima, Japan.
Sadao
S
Tanaka
Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Kyoto, Japan.
Kyoichi
K
Takaori
Department of Biochemistry and Molecular Biology, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
Surinder K
SK
Batra
Department of Human Pathology, Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Kagoshima, Japan.
Suguru
S
Yonezawa
D002288:Adenocarcinoma, Mucinous / Q000175:diagnosis* / Q000235:genetics; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis* / Q000235:genetics; D045744:Cell Line, Tumor; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018396:Mucin-1 / Q000235:genetics*; D055262:Mucin-2 / Q000235:genetics*; D055264:Mucin-4 / Q000235:genetics*; D010183:Pancreatic Ducts / Q000378:metabolism / Q000473:pathology; D010189:Pancreatic Juice / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000235:genetics
D018396:Mucin-1; D055262:Mucin-2; D055264:Mucin-4