title: LC3, an autophagosome marker, is highly expressed in gastrointestinal cancers.
abstract: Autophagy is a bulk protein and organelle degradation process essential for cell maintenance and viability. Microtubule-associated protein 1 light chain 3 (LC3), the mammalian homologue of yeast Atg8, is involved in autophagosome formation during autophagy. The aim of this study was to investigate LC3 expression in gastrointestinal cancers to elucidate the role of autophagy in human cancer development. We evaluated LC3 expression by immunohistochemistry in 163 gastrointestinal cancers including 106 esophageal, 38 gastric and 19 colorectal cancers. Seventy precancerous intraepithelial neoplasias were found in esophageal cancer specimens. LC3 expression was compared with Ki-67 staining and expression of carbonic anhydrase (CA) IX, a hypoxic marker. LC3 was expressed in the cytoplasm of cancer cells, but not in noncancerous epithelial cells. A high expression of LC3 was observed in 53% of esophageal, 58% of gastric and 63% of colorectal cancers. LC3 immunoreactive score gradually increased during early esophageal carcinogenesis in low- and high-grade intraepithelial neoplasia and T1 carcinoma, while it did not change in later cancer progression (T2-T4 carcinomas). In early esophageal carcinogenesis, LC3 expression correlated with Ki-67 labeling index (p=0.0001), but showed no significant association with CAIX expression. In esophageal cancers, LC3 expression did not correlate with various clinicopathological factors, including survival. LC3 is upregulated in various gastrointestinal cancers and partly associated with Ki-67 index. Our results suggest that LC3 expression is advantageous to cancer development especially in early-phase carcinogenesis.
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Yoshioka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyata
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
authors.forename: Makoto
authors.initials: M
authors.lastname: Yamasaki
authors.forename: Itsuro
authors.initials: I
authors.lastname: Sohma
authors.forename: Kunihito
authors.initials: K
authors.lastname: Gotoh
authors.forename: Shuji
authors.initials: S
authors.lastname: Takiguchi
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Uchiyama
authors.forename: Morito
authors.initials: M
authors.lastname: Monden
mesh_terms: D000368:Aged; D001343:Autophagy / Q000502:physiology*; D015153:Blotting, Western; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D010588:Phagosomes / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins