title: Autophagy is activated in pancreatic cancer cells and correlates with poor patient outcome.
abstract: Because autonomous proliferating cancer cells are often exposed to hypoxic conditions, there must be an alternative metabolic pathway, such as autophagy, that allows them to obtain energy when both oxygen and glucose are depleted. We previously reported finding that autophagy actually contributes to cancer cell survival in colorectal cancers both in vitro and in vivo. Pancreatic cancer remains a devastating and poorly understood malignancy, and hypoxia in pancreatic cancers is known to increase their malignant potential. In the present study archival pancreatic cancer tissue was retrieved from 71 cases treated by curative pancreaticoduodenectomy. Autophagy was evaluated by immunohistochemical staining with anti-LC3 antibody, as LC3 is a key component of autophagy and has been used as a marker of autophagy. The results showed that strong LC3 expression in the peripheral area of pancreatic cancer tissue was correlated with a poor outcome (P = 0.0170) and short disease-free period (P = 0.0118). Two of the most significant correlations among the clinicopathological factors tested were found between the peripheral intensity level of LC3 expression and tumor size (P = 0.0098) or tumor necrosis (P = 0.0127). Activated autophagy is associated with pancreatic cancer cells, and autophagy is thought to be a response to factors in the cancer microenvironment, such as hypoxia and poor nutrient supply. This is the first study to report the clinicopathological significance of autophagy in pancreatic cancer.
authors.affiliation: Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fujii
authors.forename: Shuichi
authors.initials: S
authors.lastname: Mitsunaga
authors.forename: Manabu
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hasebe
authors.forename: Genichiro
authors.initials: G
authors.lastname: Ishii
authors.forename: Motohiro
authors.initials: M
authors.lastname: Kojima
authors.forename: Taira
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Takashi
authors.initials: T
authors.lastname: Ueno
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Esumi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ochiai
mesh_terms: D000368:Aged; D001343:Autophagy; D015415:Biomarkers; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000473:pathology* / Q000601:surgery; D016577:Pancreaticoduodenectomy
chemical_list: D015415:Biomarkers; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins