title: The serine protease HtrA1 is a novel prognostic factor for human mesothelioma.
abstract: 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.
authors.affiliation: Department of Biochemistry and Biophysics, Section of Pathology, Second University of Naples, Via L Armanni 5, 80138 Naples, Italy. alfonsobaldi@tiscali.it
authors.forename: Alfonso
authors.initials: A
authors.lastname: Baldi
authors.forename: Marcella
authors.initials: M
authors.lastname: Mottolese
authors.forename: Bruno
authors.initials: B
authors.lastname: Vincenzi
authors.forename: Mara
authors.initials: M
authors.lastname: Campioni
authors.forename: Pasquale
authors.initials: P
authors.lastname: Mellone
authors.forename: Mariapia
authors.initials: M
authors.lastname: Di Marino
authors.forename: Vincenzo G
authors.initials: VG
authors.lastname: di Crescenzo
authors.forename: Paolo
authors.initials: P
authors.lastname: Visca
authors.forename: Simona
authors.initials: S
authors.lastname: Menegozzo
authors.forename: Enrico P
authors.initials: EP
authors.lastname: Spugnini
authors.forename: Gennaro
authors.initials: G
authors.lastname: Citro
authors.forename: Anna
authors.initials: A
authors.lastname: Ceribelli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mirri
authors.forename: Jeremy
authors.initials: J
authors.lastname: Chien
authors.forename: Viji
authors.initials: V
authors.lastname: Shridhar
authors.forename: Michael
authors.initials: M
authors.lastname: Ehrmann
authors.forename: Mario
authors.initials: M
authors.lastname: Santini
authors.forename: Francesco
authors.initials: F
authors.lastname: Facciolo
mesh_terms: 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
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases