title: Clinicopathological implications of expressions of hypoxia-related molecules in esophageal superficial squamous cell carcinoma.
abstract: This study was conducted to clarify whether or not expressions of hypoxia-related molecules would have clinicopathological significance in squamous cell carcinoma (SCC) of the esophagus. Expressions of hypoxia inducible factor-1 alpha (HIF-1alpha), glucose transporter 1 (GLUT-1) and RAC-1 were immunohistochemically analyzed in 96 surgically resected SCCs at pT1b (sm1, 12 cases; sm2, 35 cases; sm3, 49 cases). They were divided into a lymph node metastasis (LNM)-positive group composed of 44 cases and an LNM-negative group composed of 52 cases. Immunohistochemical profiles were estimated based on the staining extent (score: 1+, 2+, 3+) and intensity (score: 1+, 2+, 3+). A significant expression pattern was found in the nucleus for HIF-1alpha, cell membrane for GLUT-1 and cytoplasm for RAC-1. The cases were categorized into a high score group (total score of 4 or more) and a low score group (total score of 3 or less) in each maker, respectively. A comparison made between the LNM-positive group and the LNM-negative group showed that the proportion of cases with a high score was larger in the LNM-positive group than in the LNM-negative group (HIF-1alpha, P = .02; GLUT-1, P = .008; RAC-1, P = .001). Among them, HIF-1alpha was found to be significantly related to the disease-free survival (P = .019) and overall survival (P = .034) as well as LNM (disease-free survival, P = .030; overall survival, P = .030). The multivariate analysis demonstrated that the HIF-1alpha expression would be an independent indicator for prognosis. In the superficial SCCs of the esophagus, GLUT-1 and RAC-1 may be involved in LNM, and HIF-1alpha overexpression is expected to predict an unfavorable clinical outcome.
authors.affiliation: Kanagawa Cancer Center Hospital, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Ogane
authors.forename: Masanori
authors.initials: M
authors.lastname: Yasuda
authors.forename: Michio
authors.initials: M
authors.lastname: Shimizu
authors.forename: Masaki
authors.initials: M
authors.lastname: Miyazawa
authors.forename: Shingo
authors.initials: S
authors.lastname: Kamoshida
authors.forename: Akiko
authors.initials: A
authors.lastname: Ueda
authors.forename: Ken
authors.initials: K
authors.lastname: Takata
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sakuma
authors.forename: Yohei
authors.initials: Y
authors.lastname: Miyagi
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kameda
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D005260:Female; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D015415:Biomarkers; D051272:Glucose Transporter Type 1; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C107953:RAC1 protein, human; C495677:SLC2A1 protein, human; D020830:rac1 GTP-Binding Protein