Tumour necrosis is an independent prognostic marker in non-small cell lung cancer: correlation with biological variables

BACKGROUND: Tumour necrosis (TN) is recognized to be a consequence of chronic cellular hypoxia. TN and hypoxia correlate with poor prognosis in solid tumours. METHODS: In a retrospective study the prognostic implications of the extent of TN was evaluated in non-small cell lung cancer (NSCLC) and correlated with clinicopathological variables and expression of epidermal growth factor receptor, Bcl-2, p53 and matrix metalloproteinase-9 (MMP-9). Tissue specimens from 178 surgically resected cases of stage I-IIIA NSCLC with curative intent were studied. The specimens were routinely processed, formalin-fixed and paraffin-embedded. TN was graded as extensive or either limited or absent by two independent observers; disagreements were resolved using a double-headed microscope. The degree of reproducibility was estimated by re-interpreting 40 randomly selected cases after a 4 month interval. RESULTS: Reproducibility was attained in 36/40 cases, Kappa score = 0.8 P < 0.001. TN correlated with T-stage (P = 0.001), platelet count (P = 0.004) and p53 expression (P = 0.031). Near significant associations of TN with N-stage (P = 0.063) and MMP-9 expression (P = 0.058) were seen. No association was found with angiogenesis (P = 0.98). On univariate (P = 0.0016) and multivariate analysis (P = 0.023) TN was prognostic. CONCLUSION: These results indicate that extensive TN reflects an aggressive tumour phenotype in NSCLC and may improve the predictive power of the TMN staging system. The lack of association between TN and angiogenesis may be important although these variables were not evaluated on serial sections.