SinaryNon-small-cell lung cancer (NSCLC) prognosis is stnrctly related to well-established clinicopathological parameters which have unfortunately become insufficient in the prognostic evaluation of this type of cancer. As p53 and bcl-2 gene deregulations are frequently involved in several types of epithelial malignancies, we investigated the Bcl-2 and p53 protein expression in 91 and 101 cases of NSCLC respectively. The expression was then compared with established indicators of prognosis and biological behaviour of the tumours. No relationship was observed between Bcl-2 and either clinicopathological or biological parameters such as histology, grading, tumour status, nodal metastasis and proliferative activity evaluated by scoring proliferating cell nuclear antigen expression and Ki-67 immunoreactivity. However, the mean Bcl-2 expression was significantly lower in patients who developed metastasis during follow-up or died of metastatic disease (P = 0.006 and P= 0.01 respectively). Moreover, survival probability was higher in patients who expressed the Bcl-2 protein (P =0.0002). In contrast with this, p53 protein accumulation was observed in tumours with metastatic nodal involvement (P = 0.02) or in patients who developed metastasis during follow-up (P = 0.01), although no correlation was found between p53 expression and overall survival. An inverse relationship was also found between Bcl-2 and the anti-oncogene protein product p53 (P = 0.01). Thus, a high proportion of NSCLCs express p53 and Bcl-2 proteins and their expression may have prognostic importance.Keywords: oncogenes; NSCLC; prognosis; p53; Bcl-2 Lung cancer has now become the leading cause of cancer deaths in both men and women in the USA (Minna et al., 1989). In particular, non-small-cell lung cancer (NSCLC) represents a heterogeneous subgroup in terms of both behaviour and therapeutic response. Several studies have clearly demonstrated that multiple genetic events are associated with the development of lung cancer, including a range of chromosomal abnormalities, mutations activating the dominant cellular proto-oncogenes and genetic events inactivating tumour suppressor genes (Minna, 1993). p53 alterations and aberrant nuclear accumulation of this protein have been recently studied with particular interest. Many experimental data indicate that the p53-suppressor gene is the most commonly altered tumour-suppressor gene (Hollstein et al., 1991). This gene codes for a nuclear phosphoprotein, normally undetectable in human cells, which is able to regulate cell growth and division (Levine et al., 1991;Lane, 1992 Croce, 1986;Aisemberg et al., 1988). This translocation places the bcl-2 gene at chromosomal location 18q21 in juxtaposition with the immunoglobulin heavy-chain locus at 14q32, resulting in transcriptional deregulation of the bcl-2 gene (Cleary et al., 1984;Tsujimoto and Croce, 1986;Tsujimoto et al., 1987) (Silvestrini et al., 1994). In contrast with lymphomas, little or no evidence of gross alterations in the bcl-2 gene structure was obtained...
The growth of newly formed vessels, or neoangiogenesis, represents an important step in both physiological and pathological situations: in particular, tumour growth and metastasis require angiogenesis. Microvessel count (MC), which represents a measure of tumour angiogenesis, has been associated with metastatic spread in cutaneous, mammary, prostatic, head and neck, and early-stage lung cancer. In this study, the role of tumour angiogenesis as a prognostic indicator was examined in 253 primary non-small lung cancer (NSCLC) patients. Microvessels were counted by highlighting endothelial cells with anti-Factor VIII monoclonal antibody (Mab) in methacarn-fixed tumour samples. In univariat analysis, MC (P< 0.000001), sex (P=0.0036), histotype (P < 0.014), tumour status (P <0.007), and vessel invasion (P < 0.019) were significantly related to hilar and/or mediastinal nodal involvement. However, in the stepwise logistic regression analysis, MC (P<0.000003) retained the most important influence on nodal metastasis. The overall survival analysis calculated by the Kaplan-Meier method revealed that tumours with high MC ( > 25 vessels/field) were significantly associated with increased death risk (log-rank test P = 0.00067; Cox's test P = 0.00046; Gehan's Wilcoxon test P = 0.00108). In 94 patients, the development of metastatic disease during follow-up was significantly related to MC. Indeed, patients who developed metastasis during follow-up showed a higher MC, either as a dichotomous (P = 0.01) or as a continuous (P = 0.003) variable, than patients who had developed no metastasis at the time of the analysis. Moreover, in the stepwise logistic regression analysis, MC retained the most important influence on distant metastases.(ABSTRACT TRUNCATED AT 250 WORDS)
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