title: Increased cyclin D3 expression significantly correlates with p27 nuclear positivity in gastrointestinal stromal tumors.
abstract: Gastrointestinal stromal tumors, the most common mesenchymal tumors of the gastrointestinal tract, are characterized by strong expression of c-Kit protein. Recently, it has been shown that gastrointestinal stromal tumors may also contain alterations of genes involved in the regulation of cell cycle. In this study, we evaluate the prevalence and clinical significance of cyclin D1 and D3, Ki-67, p27, and retinoblastoma protein expression in a group of 50 human gastrointestinal stromal tumors selected from the files of the Moffitt Cancer Center. Tissue sections from each case were subjected to immunostaining using the avidin-biotin complex method. Cyclin D1 nuclear positivity was detected in 21 of 50 (42%) and cyclin D3 in 24 of 50 (48%) cases. p27 high immunoreactivity and negative or decreased retinoblastoma protein expression were identified in 33 of 50 (66%) gastrointestinal stromal tumors. In 19 of 50 (38%) tumors, Ki-67 had high labeling index. Direct correlation was observed between cyclin D3 and p27 expression (P < .0001), and between cyclin D1 and retinoblastoma protein (P = .03). Coexpression of cyclin D3 and p27 was demonstrated by immunofluorescence. The p27 protein expression inversely correlated with tumor size (P = .004), but was not correlated with tumor grade (P = .12). Ki-67 directly correlated with both tumor size (P = .03) and tumor grade (P = .008). We report a direct correlation between cyclin D3 and p27 expression in gastrointestinal stromal tumors. Additional alterations in cyclin D1, Ki-67, and retinoblastoma protein expression indicate a disregulated cell cycle in these tumors.
authors.affiliation: Department of Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612-9497, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Draper
authors.forename: Marilyn
authors.initials: M
authors.lastname: Bui
authors.forename: David C
authors.initials: DC
authors.lastname: Boulware
authors.forename: Mark
authors.initials: M
authors.lastname: Lloyd
authors.forename: Alberto A
authors.initials: AA
authors.lastname: Chiappori
authors.forename: Warren J
authors.initials: WJ
authors.lastname: Pledger
authors.forename: Domenico
authors.initials: D
authors.lastname: Coppola
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism* / Q000473:pathology; D056743:Cyclin D3; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000378:metabolism*; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016160:Retinoblastoma Protein / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C534696:CCND3 protein, human; C436291:CDKN1B protein, human; D056743:Cyclin D3; D016213:Cyclins; D047908:Intracellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen; D016160:Retinoblastoma Protein; D050760:Cyclin-Dependent Kinase Inhibitor p27