Tumor-associated alterations in caspase-14 expression in epithelial malignancies. Clin Cancer Res 2005 Aug 01;11(15):5462-71
Date
08/03/2005Pubmed ID
16061862DOI
10.1158/1078-0432.CCR-04-2527Scopus ID
2-s2.0-23044517098 (requires institutional sign-in at Scopus site) 58 CitationsAbstract
PURPOSE: Caspase-14 is unique among caspase family proteases in that its proteolytic processing has been principally associated with epithelial cell differentiation rather than apoptosis or inflammation. We investigated caspase-14 expression in several types of human epithelial malignancy by immunohistochemistry, correlating results with stage, histologic grade, and patient survival.
EXPERIMENTAL DESIGN: Tumor-associated alterations in caspase-14 expression were observed for cervical, ovarian, breast, gastric, and colon cancers.
RESULTS: In cervical (n = 445), ovarian (n = 91), and colon (n = 106) specimens, expression of caspase-14 was significantly reduced in cancers compared with normal epithelium. Decreases in caspase-14 immunopositivity correlated with the histologic progression of cervical cancer (P < 0.0001, ANOVA). In localized gastric cancers, caspase-14 immunostaining was significantly lower in poorly differentiated tumors compared with well-differentiated tumors (P = 0.02, Pearson's chi(2) analysis). Lower caspase-14 expression was associated with advanced clinical stage in ovarian cancer (P = 0.04, ANOVA) and with shorter overall survival among ovarian cancer patients with serous tumors (n = 62) in both univariate (P = 0.005) and multivariate (P = 0.03) analysis. Lower caspase-14 expression correlated with shorter overall survival among patients with T(3)N(0)M(0) stage gastric cancers (n = 94; P = 0.006, log-rank test). In contrast to cervical, ovarian, and colon cancers, caspase-14 expression was increased in ductal carcinoma in situ and invasive cancers compared with normal mammary epithelium (P = 0.001, t test).
CONCLUSIONS: The findings reveal tumor-specific alterations in caspase-14 expression and suggest that differences in its expression may define subsets of epithelial cancers with distinct clinical behaviors.
Author List
Krajewska M, Kim H, Shin E, Kennedy S, Duffy MJ, Wong YF, Marr D, Mikolajczyk J, Shabaik A, Meinhold-Heerlein I, Huang X, Banares S, Hedayat H, Reed JC, Krajewski SAuthor
Hirad S. Hedayat MD Associate Professor in the Neurosurgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Biomarkers, TumorCaspase 14
Caspases
Cell Differentiation
Cell Line, Tumor
Colonic Neoplasms
Disease Progression
Female
Humans
Immunoblotting
Immunohistochemistry
Microsatellite Repeats
Neoplasms, Glandular and Epithelial
Oligonucleotide Array Sequence Analysis
Ovarian Neoplasms
Proportional Hazards Models
Stomach Neoplasms
Time Factors
Uterine Cervical Neoplasms