Downregulation of cornulin in esophageal squamous cell carcinoma

• Published in: Acta histochemica Vol. 115; no. 2; pp. 89 - 99
• Main Authors: Pawar, Harsh, Maharudraiah, Jagadeesha, Kashyap, Manoj Kumar, Sharma, Jyoti, Srikanth, Srinivas Manda, Choudhary, Robin, Chavan, Sandip, Sathe, Gajanan, Manju, Hosuru Chikkalingaiah, Kumar, Kariyanakatte Veeraiah Veerendra, Vijayakumar, Manavalan, Sirdeshmukh, Ravi, Harsha, Hindahally Chandregowda, Prasad, Thottethodi Subrahmanya Keshava, Pandey, Akhilesh, Kumar, Rekha Vijay
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01-03-2013
• Subjects: Adult; Aged; Amino Acid Sequence; C1Orf10; Carcinoma, Squamous Cell - metabolism; Cell Differentiation; Cell Line, Tumor; Cell Nucleus - metabolism; Cytoplasm - metabolism; Down-Regulation; Epidermal differentiation complex; Esophageal Neoplasms - metabolism; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Loss of heterozygosity; Male; Mass Spectrometry; Membrane Proteins - metabolism; Middle Aged; Molecular Sequence Data; Neoplasm Proteins - metabolism; Oligonucleotide Array Sequence Analysis; S100 gene family; S100 Proteins - metabolism; Squamous epithelial-induced stress protein of 53 kDa; Stress response protein; Stress response protein; LOH; EDC; EAC; SFTP; TMA; Squamous epithelial-induced stress protein of 53kDa; S100 gene family; ESCC; SEP53; CRNN; Loss of heterozygosity; iTRAQ; Epidermal differentiation complex; C1Orf10; Mass spectrometry
• ISSN: 0065-1281; 1618-0372
• DOI: 10.1016/j.acthis.2012.04.003

Early events in the development of esophageal squamous cell carcinoma (ESCC) are poorly understood and many of the key molecules involved have not yet been identified. We previously used isobaric tags for a relative and absolute quantitation (iTRAQ)-based quantitative proteomics approach to identify differentially expressed proteins in ESCC tissue as compared to the adjacent normal mucosa. Cornulin was identified as one of the major downregulated molecules in ESCC. Cornulin is a member of the S100 fused-type protein family, which has an EF-hand calcium binding motif and multiple tandem repeats of specific peptide motifs. Cornulin was 5-fold downregulated in ESCC as compared to normal epithelium mirroring our previous findings in a gene expression study of ESCC. In the present study, we performed immunohistochemical validation of cornulin (CRNN) in a larger set of patients with ESCC. Downregulation of cornulin was observed in 89% (n=239) of 266 different ESCC tissues arrayed on tissue microarrays (TMAs). Expression of cornulin was observed in the prickle and functional cell layers of normal esophageal mucosa, localized predominantly in the cytoplasm and perinuclear region. The large majority of ESCC cases had little or no expression of cornulin in the carcinoma or stroma. These findings suggest that cornulin is an important molecule in normal esophageal pathology and is likely lost during the conversion of normal to neoplastic epithelium.