Tumor-Associated Alterations in Caspase-14 Expression in Epithelial Malignancies
| Autor: | John C. Reed, Michael J. Duffy, Steven Banares, Hoguen Kim, David Marr, Jowita Mikolajczyk, Maryla Krajewska, Ahmed Shabaik, Yick Fu Wong, Xianshu Huang, Susan Kennedy, Hirad Hedayat, Ivo Meinhold-Heerlein, Stan Krajewski, Eunah Shin |
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| Rok vydání: | 2005 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty Time Factors Immunoblotting Uterine Cervical Neoplasms Biology Stomach Neoplasms Cell Line Tumor Biomarkers Tumor medicine Caspase 14 Humans Neoplasms Glandular and Epithelial Oligonucleotide Array Sequence Analysis Proportional Hazards Models Epithelial cell differentiation Ovarian Neoplasms Cervical cancer Cell Differentiation Ductal carcinoma medicine.disease Histologic Progression Immunohistochemistry Serous fluid Oncology Caspases Colonic Neoplasms Disease Progression Female Ovarian cancer Microsatellite Repeats |
| Zdroj: | Clinical Cancer Research. 11:5462-5471 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-04-2527 |
| Popis: | 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 χ2 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 T3N0M0 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. |
| Databáze: | OpenAIRE |
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