title: Pdcd4 expression in intraductal papillary mucinous neoplasm of the pancreas: its association with tumor progression and proliferation.
abstract: Intraductal papillary mucinous neoplasm is characterized by cystically dilated main and/or branch pancreatic duct with mucus. According to the degree of atypia, intraductal papillary mucinous neoplasm is classified into 3 groups: adenoma, borderline, and carcinoma. Furthermore, intraductal papillary mucinous neoplasm is considered to progress through an adenoma-carcinoma sequence like colorectal carcinoma. Programmed cell death 4 is a recently identified tumor suppressor that was found to inhibit translation. Programmed cell death 4 has been reported to inhibit tumorigenesis, tumor progression, proliferation, invasion, and metastasis in several human malignancies. We examined 108 cases of intraductal papillary mucinous neoplasm by immunohistochemistry and revealed that programmed cell death 4 expression was recognized in both the nucleus and cytoplasm in intraductal papillary mucinous neoplasm. The positive rate of programmed cell death 4 was 79%, 43%, and 10% in adenoma, borderline, and carcinoma, respectively. The positive rate of programmed cell death 4 decreased from adenoma to carcinoma (P < .0001, both adenoma versus borderline and borderline versus carcinoma), indicating that programmed cell death 4 might inhibit tumor progression in intraductal papillary mucinous neoplasm. Programmed cell death 4 expression had a strong relationship with p21 expression (P < .0001) and an inverse correlation with Ki-67 labeling index (r = -0.6255, P < .0001). Thus, programmed cell death 4 might inhibit the proliferation of intraductal papillary mucinous neoplasm; and its inhibition might partly result from cell cycle arrest caused by the up-regulation of p21. In conclusion, programmed cell death 4 may inhibit tumor progression in intraductal papillary mucinous neoplasm; and the loss of programmed cell death 4 expression is representative of the malignant potential of intraductal papillary mucinous neoplasm including the proliferative activity. Therefore, programmed cell death 4 can be an important biomarker for intraductal papillary mucinous neoplasm.
authors.affiliation: Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University 3-1-1 Maidashi, Fukuoka, 812-8582, Japan.
authors.forename: Akifumi
authors.initials: A
authors.lastname: Hayashi
authors.forename: Shinichi
authors.initials: S
authors.lastname: Aishima
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Miyasaka
authors.forename: Kohei
authors.initials: K
authors.lastname: Nakata
authors.forename: Katsuya
authors.initials: K
authors.lastname: Morimatsu
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Oda
authors.forename: Eishi
authors.initials: E
authors.lastname: Nagai
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Oda
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
authors.forename: Masazumi
authors.initials: M
authors.lastname: Tsuneyoshi
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000231:Adenocarcinoma, Papillary / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000236:Adenoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D019085:Fluorescent Antibody Technique, Direct; D006801:Humans; D007564:Japan / Q000453:epidemiology; D019394:Ki-67 Antigen / Q000378:metabolism; D010183:Pancreatic Ducts / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016601:RNA-Binding Proteins / Q000378:metabolism*; D015996:Survival Rate
chemical_list: D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins