Prognostic value of the expression of p53, bcl-2, and bax oncoproteins, and neovascularization in patients with radically resected non-small-cell lung cancer.

PURPOSE: To assess the prognostic value of p53, bcl-2, bax, and neovascularization in radically resected non-small-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: Tumors from 116 patients were assessed by immunohistochemistry for expression of p53 (DO7 and PAb1081), bcl-2, and the quantification of microvessel density (CD-31). In addition, the expression of bax was assessed in 61 stage I tumors. The median levels of expression of each marker were used as cutoff points. RESULTS: p53 was not correlated to any patient or tumor characteristic, whereas bcl-2 showed higher expression in squamous cell carcinomas (P < .001). bax expression was significantly related with male sex (P = .006) and adenocarcinoma type (P = .0013). p53 status, assessed with one monoclonal antibody (MoAb), was not predictive for survival; however, the combination of staining results obtained with two MoAbs identified the DO7-/PAb1801+ tumors as those with the worst prognosis. bcl-2 expression was associated with longer survival in stage I patients (P = .0169). The combined group expressing p53+(PAb1801)/bcl-2- had the worst survival in stage I patients (P = .034) and in the whole series in comparison with the other combinations of the two oncoproteins. bax expression alone had no influence on survival of stage I patients, but patients with bax+/bcl-2- tumors had the worst prognosis (P = .02 in comparison with bax+/bcl-2+). Tumor neovascularization was not related with other factors, and patients with CD-31+ tumors had a shorter survival duration than those with CD-31- tumors only in stage II (P = .0283). By multivariate analysis including all patients, the presence of p53+/ bcl-2- tumor expression and large tumor diameter (> or = 4cm) were independent prognostic factors for shorter survival duration. For stage I, only the presence of bax+/ bcl-2- tumor expression had a significant negative influence on survival. CONCLUSION: The interaction and the regulation of new biologic markers, such as those involved in the apoptotic pathway, are complex. Combinations of the expression of several of them may give more valuable information than the study of just one. Prognostic influence of p53 staining varied depending on the choice of antibody and the combination of bcl-2- together with p53+ (PAb1801) or with bax+ had the worst influence on survival for patients with stage I NSCLC.

Expression of the human major vault protein LRP in human lung cancer samples and normal lung tissues.

BACKGROUND: The recently discovered LRP protein has been shown to be involved in drug resistance and possibly in detoxification processes. MATERIALS AND METHODS: To study the relation between LRP expression and exposure to cigarette smoke, LRP immunoreactivity was evaluated in 39 paraffin embedded normal lung tissues derived from patients operated on for pneumothorax, and related to amount of pack years smoked. We also studied the LRP protein expression in 36 non-small-cell lung cancer (NSCLC) samples and related the expression to patient characteristics and survival. Furthermore 17 lung tumor samples (10 NSCLC and 7 SCLC) derived from patients treated with chemotherapy were analysed in order to investigate the relation between LRP or MRP expression and the patient's response to chemotherapy. RESULTS: In the normal lung tissues, LRP intensity levels were not correlated to the amount of pack years smoked, although a trend was seen for higher LRP intensity levels in patients who smoked more than 10 pack years. LRP expression was significantly higher in NSCLC samples than in SCLC samples, and all SCLC samples displayed very low LRP expression. Within NSCLC, squamous cell and adenocarcinomas had higher LRP expression than large cell undifferentiated and mixed tumors. In NSCLC patients LRP expression was not a prognostic factor for survival. At initial analysis LRP expression levels did not predict for the response to chemotherapy. Only 3 out of 17 patients expressed MRP, and all SCLC samples were MRP negative. CONCLUSIONS: Striking different expression levels were seen between NSCLC and SCLC for both LRP and MRP. In a preliminary analysis LRP expression was not predictive for response to chemotherapy in lung cancer patients. In pneumothorax patients LRP levels were not correlated with the amount of pack years smoked.