Research Information System
Annals of Medical Sciences, vol.8, no.1, pp.14-21, 1999 (Scopus)
Purpose: The biologic significance of tumour heterogeneity including neuroendocrine differentiation in non small cell lung carcinomas is not certain. The purpose of this study is to investigate whether there is any significant difference between non small cell carcinomas with and without tumour heterogeneity including neuroendocrine differentiation in terms of tumour stage, tumour suppressor gene alterations shown by p53 protein expression and proliferative activity shown by PCNA expression. Methods: Paraffin sections of 57 non small cell carcinomas were reviewed and microscopic tumour heterogeneity was evaluated. The sections were all stained with neuroendocrine markers including Neuron Specific Enolase, Chromogranin A, Calcitonin and Serotonin antibodies for the evaluation of neuroendocrine differentiation, with anti-PCNA antibody for the evaluation of the proliferative activity of tumours, and with p53 antibody for the detection of mutant nuclear p53 protein expression. Standard streptavidin biotin immunperoxidase method was used for immunohistochemical staining. Fifty seven cases were graded for cytoplasmic staining with NE markers on a scale of 0 (-), to 3 positive(+). Nuclear staining for p53 was semiquantitatively graded as follows: (-): no staining, 1+: 1-30% of cells stained, 2+: 30-70% of cells stained, 3+: 70% or more stained cells. Nuclear staining for PCNA was evaluated by counting 1000 tumour cells and graded as follows: 1+: 1-40% of cells stained, 2+: 40-75% of cells stained, 3+: 75% or more cells stained. Results: Tumour heterogeneity was found in 12% of non small cell lung carcinomas on routine sections. Tumours with and without heterogenous areas did not show statistically significant difference in terms of tumour stage, proliferative activity and p53 expression. five percent of 57 non-small cell carcinomas reacted with two neuroendocrine markers. 42% of cases were positive for only one neuroendocrine marker. There was no statistically significant difference between the cases which were negative and cases which were positive with 1 or 2 neuroendocrine markers, in terms of proliferative activity and p53 expression. Seventy-one percent of 57 non small cell carcinomas reacted with p53 antibody. Cases with p53 protein expression were not different from negative cases in terms of proliferative activity, neuroendocrine differentiation and tumour stage. All cases of non small cell carcinomas reacted with PCNA antibody with the mean staining index of 61.6%. PCNA staining indices did not show statistically significant difference between subtypes and tumour stages. Conclusion: A complete NE differention demonstrated by positivity for multiple NE markers similar to NE tumours is quite unusual. Heterogeneity and neuroendocrine differentiation in NSCLCs shown by light microscopy or by one or two NE marker positivity does not correlate with tumours stage which is the most valuable predictor of prognosis and with other factors like p53 and PCNA reactivity whose influence on prognosis is debatable.