Biological markers in non-small cell lung cancer. Retrospective study of 10 year follow-up after surgery.
BACKGROUND
The biological markers in non-small cell lung cancer (NSCLC) have been widely studied and encouraging results have shown that products of some oncogenes and other molecular markers can predict the aggressiveness of the disease and the outcome of the patients.


METHODS
To verify the reliability of these prognostic markers we have studied retrospectively the expression of c-erbB-2 and 67Ki (growth regulation), p53 (cell cycle regulation and apoptosis), bcl-2 (apoptosis) and CD31 and CD34 (angiogenesis) in 78 patients operated on for NSCLC with curative intent between January 1987 and December 1988 and followed up for 10 years. For the determination of the biological markers we have used the ABC (Avidin-Biotin-Peroxidase complex) immunohistochemical method. The Cox regression model was used for the univariate and multivariate analysis.


RESULTS
Nineteen patients (24%) were alive after 10 years and 59 (76%) died. The univariate analysis of the relationship between the 10-year survival and the expression of the markers was significant only for p53 (p=0.0097). Stratifying the patients according to the 3 histological subtypes (squamous cell carcinoma, adenocarcinoma and large cell undifferentiated carcinoma) the correlation between markers and survival pointed out that the only significant one was p53 (p=0.0459) in adenocarcinoma. In the same way considering the stages p53 was significant in stage IIIa (p=0.0357). The multivariate analysis emphasized that p53 was the only significant marker with respect to the 10-year survival (p=0.0091). Examining the histological groups significant was only p53 in adenocarcinoma (p=0.0192) and in large cell undifferentiated carcinomas (p=0.0290). This marker is also significant in pathological stage II (p=0.0271) and IIIa (p=0.0402). Apart from histology and staging the 10-year survival was 33% for p53 negative versus 10% for p53 positive. In patients with adenocarcinoma the 10-year survival was 40% for p53 negative and 6% for p53 positive.


CONCLUSIONS
In conclusion our results emphasize the importance of p53 as a prognostic factor in 10-year survival in patients with adenocarcinoma and in stage II and IIIa.
Carbognani
P
P
Department of Thoracic and Vascular Surgery, University of Parma, Italy. Paolo.Carbognani@Unipr.It
Tincani
G
G
Crafa
P
P
Sansebastiano
G
G
Pazzini
L
L
Zoni
R
R
Bobbio
A
A
Rusca
M
M
D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000401:mortality / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D016016:Proportional Hazards Models; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D012189:Retrospective Studies; D015996:Survival Rate; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019253:Proto-Oncogene Proteins c-bcl-2; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53