Extent of tumor removal and molecular markers in cerebral glioblastoma: a combined prognostic factors study in a surgical series of 105 patients.
OBJECTIVE
In this paper, the authors' goal was to evaluate the prognostic value of YKL-40 expression as a prognostic factor for glioblastomas and to compare its validity to the already known MGMT.


METHODS
Between January 2002 and January 2007, 105 patients were treated for cerebral glioblastoma. The extent of removal was classified in 4 groups. YKL-40 expression was evaluated by a semiquantitative immunohistochemical staining scale (0, no staining; 1, mild expression; and 2, strong expression). MGMT promoter methylation status was analyzed with methylation-specific polymerase chain reaction. All patients received adjuvant radiotherapy and chemotherapy. Kaplan-Meier curves were used to analyze progression-free survival (PFS) and overall survival (OS), and to compare these parameters between the subgroups stratified by extent of surgical removal, MGMT methylation, and YKL-40 expression. The log-rank test was used to determine statistical significance. A multivariate regression analysis was applied to extent of removal, YKL-40 expression, and MGMT status to check their specific statistical power and to test the independence of the variables.


RESULTS
There were 55 men and 50 women with a mean age of 58 years. Extent of surgical removal is reported. The MGMT promoter was methylated in 48 patients and nonmethylated in 57. Analysis of YKL-40 expression is reported. The median PFS was 10.7 months (14.9 months in the gross-total removal subgroup) (p < 0.0001), and the median OS was 12.5 months (17.4 months in the gross-total removal group) (p < 0.0001). In the univariate analysis, OS was significantly correlated to the extent of resection (p < 0.0001), MGMT status (p < 0.0001), and YKL-40 (p < 0.0001). Multivariate analysis showed that all 3 factors reached statistical significance with respect to patient survival. In particular, surgical removal contributed more than the 2 other factors to the survival prediction (β = -0.6254). Interestingly, YKL-40 (β = -0.3867) contributed more than MGMT (β = -0.1705) to the predicted survival.


CONCLUSIONS
The extent of removal is the most important factor influencing the OS of patients harboring glioblastomas. When biological aggressiveness is taken into account, YKL-40 expression was found to be an independent prognostic factor that predicts OS better than MGMT status.
Department of Neurosurgery INM-IRCCS Neuromed, Pozzilli (Isernia), University of Rome "Sapienza;" Italy. salvati.maurizio@libero.it.
Maurizio
M
Salvati
Angelo
A
Pichierri
Manolo
M
Piccirilli
Giacoma Maria
GM
Floriana Brunetto
Alessandro
A
D'Elia
Spartaco
S
Artizzu
Francesca
F
Santoro
Antonietta
A
Arcella
Felice
F
Giangaspero
Alessandro
A
Frati
Luca
L
Simione
Antonio
A
Santoro
D054392:Adipokines / Q000235:genetics*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D000071451:Chitinase-3-Like Protein 1; D019175:DNA Methylation / Q000235:genetics; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D006801:Humans; D007124:Immunoenzyme Techniques; D053208:Kaplan-Meier Estimate; D037102:Lectins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D054392:Adipokines; D014408:Biomarkers, Tumor; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D037102:Lectins; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes