ABSTRACT
We evaluated immunohistochemically the expression of two negative regulators of the cell cycle, namely retinoblastoma gene product (pRb) and WAF1/Cip1 gene product (p21), in paraffin sections from 93 patients with non-Hodgkin's lymphomas (NHL) and related it to clinicopathological parameters, proliferative fraction, p53 expression and survival. Patients were followed until death (n=33) or for an average of 52 months (60-160). Rb labelling index (LI) increased with malignancy grade and proliferative activity but was unrelated to other clinicopathological parameters. In 33% of cases, especially those of the aggressive groups, we observed diminished pRb expression (i.e. low pRb/Ki-67 ratio). p21 expression on the other hand correlated only with histological grade, Rb LI and p53 LI. In multivariate analysis, Rb LI was a negative predictor of disease-free survival but was linked to a higher probability of complete response. However, diminished pRb expression as well as p21 expression were not statistically significant prognostic indicators. Our results suggest that pRb as a cell cycle related molecule may play an important role in determining prognosis and therapeutic response in NHL patients.
Subject(s)
Cyclins/genetics , Genes, Retinoblastoma , Lymphoma, Non-Hodgkin/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor , Cyclin-Dependent Kinase Inhibitor p21 , Cyclins/metabolism , Female , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Lymphoma, Non-Hodgkin/metabolism , Lymphoma, Non-Hodgkin/mortality , Lymphoma, Non-Hodgkin/pathology , Lymphoma, Non-Hodgkin/physiopathology , Male , Middle Aged , Multivariate Analysis , Survival AnalysisABSTRACT
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.
