title: Downregulation of S100 Calcium Binding Protein A9 in Esophageal Squamous Cell Carcinoma.
abstract: The development of esophageal squamous cell carcinoma (ESCC) is poorly understood and the major regulatory molecules involved in the process of tumorigenesis have not yet been identified. We had previously employed a quantitative proteomic approach to identify differentially expressed proteins in ESCC tumors. A total of 238 differentially expressed proteins were identified in that study including S100 calcium binding protein A9 (S100A9) as one of the major downregulated proteins. In the present study, we carried out immunohistochemical validation of S100A9 in a large cohort of ESCC patients to determine the expression and subcellular localization of S100A9 in tumors and adjacent normal esophageal epithelia. Downregulation of S100A9 was observed in 67% (n = 192) of 288 different ESCC tumors, with the most dramatic downregulation observed in the poorly differentiated tumors (99/111). Expression of S100A9 was restricted to the prickle and functional layers of normal esophageal mucosa and localized predominantly in the cytoplasm and nucleus whereas virtually no expression was observed in the tumor and stromal cells. This suggests the important role that S100A9 plays in maintaining the differentiated state of epithelium and suggests that its downregulation may be associated with increased susceptibility to tumor formation.
authors.affiliation: Institute of Bioinformatics, International Technology Park, Bangalore 560066, India; Rajiv Gandhi University of Health Sciences, Bangalore 560041, India; Department of Pathology, Kidwai Memorial Institute of Oncology, Bangalore 560029, India; Department of Zoology, Savitribai Phule Pune University, Ganeshkhind, Pune, Maharashtra 411007, India.
authors.forename: Harsh
authors.initials: H
authors.lastname: Pawar
authors.affiliation: Institute of Bioinformatics, International Technology Park, Bangalore 560066, India; Centre of Excellence in Bioinformatics, School of Life Sciences, Pondicherry University, Pondicherry 605014, India.
authors.forename: Srinivas M
authors.initials: SM
authors.lastname: Srikanth
authors.affiliation: Institute of Bioinformatics, International Technology Park, Bangalore 560066, India; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093-0960, USA.
authors.forename: Manoj Kumar
authors.initials: MK
authors.lastname: Kashyap
authors.affiliation: Institute of Bioinformatics, International Technology Park, Bangalore 560066, India.
authors.forename: Gajanan
authors.initials: G
authors.lastname: Sathe
authors.affiliation: Institute of Bioinformatics, International Technology Park, Bangalore 560066, India.
authors.forename: Sandip
authors.initials: S
authors.lastname: Chavan
authors.affiliation: Government Medical College and Hospital, Sector 32, Chandigarh 160030, India.
authors.forename: Mukul
authors.initials: M
authors.lastname: Singal
authors.affiliation: Department of Pathology, Kidwai Memorial Institute of Oncology, Bangalore 560029, India.
authors.forename: H C
authors.initials: HC
authors.lastname: Manju
authors.affiliation: Department of Surgical Oncology, Kidwai Memorial Institute of Oncology, Bangalore 560029, India.
authors.forename: Kariyanakatte Veeraiah Veerendra
authors.initials: KV
authors.lastname: Kumar
authors.affiliation: Department of Surgical Oncology, Kidwai Memorial Institute of Oncology, Bangalore 560029, India.
authors.forename: M
authors.initials: M
authors.lastname: Vijayakumar
authors.affiliation: Institute of Bioinformatics, International Technology Park, Bangalore 560066, India.
authors.forename: Ravi
authors.initials: R
authors.lastname: Sirdeshmukh
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Akhilesh
authors.initials: A
authors.lastname: Pandey
authors.affiliation: Institute of Bioinformatics, International Technology Park, Bangalore 560066, India; Centre of Excellence in Bioinformatics, School of Life Sciences, Pondicherry University, Pondicherry 605014, India.
authors.forename: T S Keshava
authors.initials: TS
authors.lastname: Prasad
authors.affiliation: Institute of Bioinformatics, International Technology Park, Bangalore 560066, India.
authors.forename: Harsha
authors.initials: H
authors.lastname: Gowda
authors.affiliation: Department of Pathology, Kidwai Memorial Institute of Oncology, Bangalore 560029, India.
authors.forename: Rekha V
authors.initials: RV
authors.lastname: Kumar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D040502:Calgranulin B / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008875:Middle Aged
chemical_list: D040502:Calgranulin B