Tumor-associated alterations in caspase-14 expression in epithelial malignancies.
OBJECTIVE
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.


METHODS
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.
Krajewska
Maryla
M
The Burnham Institute, La Jolla, California, USA.
Kim
Hoguen
H
Shin
Eunah
E
Kennedy
Susan
S
Duffy
Michael J
MJ
Wong
Yick F
YF
Marr
David
D
Mikolajczyk
Jowita
J
Shabaik
Ahmed
A
Meinhold-Heerlein
Ivo
I
Huang
Xianshu
X
Banares
Steven
S
Hedayat
Hirad
H
Reed
John C
JC
Krajewski
Stan
S
D014408:Biomarkers, Tumor / Q000378:metabolism; D053456:Caspase 14; D020169:Caspases / Q000235:genetics* / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D018895:Microsatellite Repeats; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000473:pathology; D016016:Proportional Hazards Models; D013274:Stomach Neoplasms / Q000473:pathology; D013997:Time Factors; D002583:Uterine Cervical Neoplasms / Q000473:pathology
D014408:Biomarkers, Tumor; C506446:CASP14 protein, human; D053456:Caspase 14; D020169:Caspases