Detection of apoptotic cells in archival tissue from diffuse astrocytomas using a monoclonal antibody to single-stranded DNA.
Precise quantitation of apoptotic cells in gliomas is necessary to determine the role of apoptosis in tumour growth, prognosis, and treatment. This study investigated the incidence of baseline apoptosis in relation to proliferation status, p53 expression, standard clinicopathological parameters, and outcome, in a series of 61 patients with diffuse cerebral astrocytomas. Apoptotic fractions were quantified immunohistochemically by means of a novel monoclonal antibody recognizing exposed single-stranded (ss) regions in the DNA of apoptotic cells during heating. Proliferative activity was expressed as the percentage of Ki-67-positive cells. Tissues consisted of primary formalin-fixed, paraffin-embedded astrocytoma specimens. The apoptotic index (AI) increased with grade, proliferative activity, and p53 expression. Increased AI tended to be accompanied by a shortened overall and disease-free survival in univariate analysis in glioblastoma multiforme and astrocytoma/anaplastic astrocytoma, respectively. Multivariate analysis demonstrated that increased AI was an independent predictor of adverse significance in overall and disease-free survival. These results implicate apoptotic rate in astrocytoma aggressiveness and show that the assessment of apoptotic potential by means of anti-ssDNA monoclonal antibody provides valuable prognostic information independently of standard parameters or tumour proliferation status.
Department of Pathology, National and Kapodistrian University of Athens, Athens 115 27, Greece. pkorkol@cc.uoa.gr
P A
PA
Korkolopoulou
A E
AE
Konstantinidou
E S
ES
Patsouris
P N
PN
Christodoulou
E A
EA
Thomas-Tsagli
P S
PS
Davaris
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000911:Antibodies, Monoclonal / Q000276:immunology; D017209:Apoptosis; D001254:Astrocytoma / Q000473:pathology*; D001932:Brain Neoplasms / Q000473:pathology*; D002455:Cell Division; D004273:DNA, Neoplasm / Q000276:immunology; D004277:DNA, Single-Stranded / Q000276:immunology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D011379:Prognosis; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000911:Antibodies, Monoclonal; D004273:DNA, Neoplasm; D004277:DNA, Single-Stranded; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53