The serine protease HtrA1 is a novel prognostic factor for human mesothelioma.
OBJECTIVE
The objective of our study was to analyze the potential prognostic value of the expression of the serine protease HtrA1 and of EGFR in 70 malignant mesotheliomas.


METHODS
Immunohistochemistry was used to determine the expression of HtrA1 and EGFR. Univariate and multivariate analyses were used to correlate expression of these molecular factors in combination with available clinicopathologic data to patient survival.


RESULTS
A positive, statistically significant relationship has been recorded between HtrA1 expression level and survival (p < 0.0001). By contrast, a negative relationship has been identified between EGFR expression and survival (p = 0.02). Moreover, extension of the tumor (T) and involvement of lymph nodes (N) advanced status (p = 0.001 and 0.002, respectively), as well as the sarcomatoid histotype (p = 0.005), correlated significantly with poor survival. Finally, by a multivariate Cox regression analysis, the only immunohistochemical parameter that resulted to influence overall survival was HtrA1 (p = 0.0001). Interestingly, the prognostic value of HtrA1 expression was completely independent from EGFR expression (p < 0.0001).


CONCLUSIONS
This is the first study of the relationship between HtrA1 expression and survival of mesothelioma patients. The data obtained strongly indicate the utilization of HtrA1 expression as a prognostic parameter for mesothelioma and suggest this serine protease as a possible molecular target for the treatment of malignant mesotheliomas.
Baldi
Alfonso
A
Department of Biochemistry and Biophysics, Section of Pathology, Second University of Naples, Via L Armanni 5, 80138 Naples, Italy. alfonsobaldi@tiscali.it
Mottolese
Marcella
M
Vincenzi
Bruno
B
Campioni
Mara
M
Mellone
Pasquale
P
Di Marino
Mariapia
M
di Crescenzo
Vincenzo G
VG
Visca
Paolo
P
Menegozzo
Simona
S
Spugnini
Enrico P
EP
Citro
Gennaro
G
Ceribelli
Anna
A
Mirri
Alessandra
A
Chien
Jeremy
J
Shridhar
Viji
V
Ehrmann
Michael
M
Santini
Mario
M
Facciolo
Francesco
F
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000096:biosynthesis; D005260:Female; D005500:Follow-Up Studies; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008654:Mesothelioma / Q000175:diagnosis* / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D012697:Serine Endopeptidases / Q000096:biosynthesis; D013534:Survival
D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases