INI1 immunohistochemical expression in glioblastoma: correlation with MGMT gene promoter methylation status and patient survival.
OBJECTIVE
INI1 expression and its correlation with MGMT gene promoter methylation status and follow-up was investigated in 77 surgically removed glioblastomas then treated with radiotherapy (RT) or RT plus temozolomide (TMZ).


METHODS
INI1 was determined by immunohistochemistry and MGMT by methylation-specific PCR.


RESULTS
INI1 was expressed in 83.1% of cases. The median overall survival (OS) was 13.6 months in INI1+ tumours and 7.2 months in INI1- tumours. 31.3% of patients with INI1+ tumours were alive compared with 15.4% of patients with INI1- tumours. MGMT methylation was detected in 31.2% of cases. OS was significantly different between patients with methylated tumours and un-methylated tumours (p < 0.04), and between patients with RT+ TMZ and RT alone (p < 0.001). Considering both treatment and MGMT, the difference in OS was significant (p < 0.002). The difference in OS according to MGMT and INI1 was significant (p < 0.04). The longest median OS was recorded among methylated and INI1+ tumours. Among un-methylated tumours, the median OS was 11.1 months in INI1+ and 6.5 months in INI1- tumours. No patients were alive with un-methylated and INI1- tumours.


CONCLUSIONS
Loss of INI1 immunohistochemical expression in glioblastoma may be indicating an underlying molecular aberration accounting for the more aggressive clinical behaviour.
Section of Pathologic Anatomy, Azienda Ospedaliero-Universitaria Policlinico di Modena, Modena, Italy. zunarelli.elena@policlinico.mo.it
Elena
E
Zunarelli
Nazzarena
N
Bigiani
Giuliana
G
Sartori
Mario
M
Migaldi
Alessandro
A
Sgambato
Antonio
A
Maiorana
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics* / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D006801:Humans; D007558:Italy / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics*; D000071796:SMARCB1 Protein; D015173:Supratentorial Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
D014408:Biomarkers, Tumor; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes