Cell proliferation and apoptosis in stage III inoperable non-small cell lung carcinoma treated by radiotherapy.
OBJECTIVE
The purpose of this study was to assess the prognostic value of the expression of p53 and bcl-2, the apoptotic index and the expression of topoisomerase II alpha in patients with inoperable non-small cell lung cancer (NSCLC) treated with high dose radiotherapy.


METHODS
A number of 161 patients with inoperable NSCLC treated with high dose radiotherapy (60 Gy) were included. Immunohistochemical analysis was used to assess the expression of nuclear p53-protein, topoisomerase II alpha and cytoplasmatic expression of bcl-2, while spontaneous apoptosis was assessed using in situ labeling. The minimal follow up period was 2 years.


RESULTS
Local control did not only depend on the presence of p53 expression, but also on the proportion of p53 positive cells. The most important prognostic factor was the apoptotic index. A high apoptotic index was associated with worse local control, more distant metastases and a significantly worse overall survival. No association was noted between the expression of bcl-2 and topoisomerase II alpha with any of the endpoints.


CONCLUSIONS
This study indicates that p53 expression and the apoptotic index are prognostic factors with regard to local control in patients with inoperable NSCLC treated with radiotherapy and by combining these 2 factors, a clinically relevant estimation of the local control probability can be made. The apoptotic index turned out to be the only factor significantly related to survival.
Radiotherapeutisch Instituut Limburg (RTIL), Heerlen, The Netherlands.
H
H
Langendijk
E
E
Thunnissen
J W
JW
Arends
J
J
de Jong
G
G
ten Velde
R
R
Lamers
D
D
Guinee
J
J
Holden
M
M
Wouters
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000528:radiation effects; D014408:Biomarkers, Tumor / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology* / Q000532:radiotherapy*; D002455:Cell Division / Q000528:radiation effects; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology* / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011336:Probability; D011379:Prognosis; D016016:Proportional Hazards Models; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis* / Q000528:radiation effects; D011878:Radiotherapy / Q000379:methods; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D019452:Terminally Ill; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000528:radiation effects
D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53