Clinical value of p53, c-erbB-2, CEA and CA125 regarding relapse, metastasis and death in resectable non-small cell lung cancer.
The prognostic value of p53 and c-erbB-2 immunostaining and preoperative serum levels of CEA and CA125 was investigated in a prospective multicentric study including 465 consecutive non-small cell lung cancer (NSCLC) patients with resectable tumors. Four end-points were used: lung cancer death, first relapse (either locoregional or metastasis), loco-regional recurrence and metastasis development. Standard statistical survival methods (Kaplan-Meier and Cox regression) were used. The specificity of the prognostic effect across different types of tumors was also explored, as had been planned in advance. Our results showed, once again, that pathological T and N classifications continue to be the strongest predictors regarding either relapse or mortality. Three of the studied markers seemed to add further useful information, however, but in a more specific context. For example, increased CEA concentration defined a higher risk population among adenocarcinomas but not among people with squamous tumors; and p53 overexpression implied a worse prognosis mainly in patients with well differentiated tumors. The analysis of type of relapse proved to be very informative. Thus, CA125 level was associated with a worse prognosis mainly related with metastasis development. Another interesting result was the influence of smoking, which showed a clear dose-response relationship with the probability of metastasis. For future studies, we recommend the inclusion of different endpoints, namely considering the relationship of markers with the type of relapse involved in lung-cancer recurrence. They can add useful information regarding the complex nature of prognosis.
Pollán
Marina
M
Instituto de Salud Carlos III, Madrid, Spain. mpollan@isciii.es
Varela
Gonzalo
G
Torres
Antonio
A
de la Torre
Mercedes
M
Ludeña
Maria Dolores
MD
Ortega
Maria Dolores
MD
Pac
Joaquín
J
Freixenet
Jorge
J
Gómez
Guillermo
G
Sebastián
Fernando
F
Díez
Manuel
M
Arrabal
Ricardo
R
Canalís
Emili
E
García-Tirado
Javier
J
Arnedillo
Aurelio
A
Rivas
Juan José
JJ
Minguella
Joan
J
Gómez
Ana
A
García
Mauricio
M
Aragonés
Nuria
N
Pérez-Gómez
Beatriz
B
López-Abente
Gonzalo
G
González-Sarmiento
Rogelio
R
Rojas
Jose María
JM
D000230:Adenocarcinoma / Q000097:blood / Q000401:mortality / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood; D018394:CA-125 Antigen / Q000097:blood*; D002272:Carcinoembryonic Antigen / Q000097:blood*; D018287:Carcinoma, Large Cell / Q000097:blood / Q000401:mortality / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000401:mortality / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000401:mortality / Q000473:pathology; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000401:mortality / Q000473:pathology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D015203:Reproducibility of Results; D016019:Survival Analysis; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D002272:Carcinoembryonic Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53