Ploidy. proliferative activity, p53 and bcl-2 expression in bronchopulmonary carcinoids: Relationship with prognosis

Bronchopulmonary well-differentiated neuroendocrine carcinoma (WDNEC) repre sents a more aggressive neoplasm than does typical carcinoid. Its biologica l behavior is variable and cannot be predicted on the basis of histopatholo gical features. Nineteen typical carcinoids and 23 WDNECs were studied in order to obtain m ultiple parameters that should be used in the differential diagnosis betwee n these two lesions and as prognostic markers of WDNEC. Flow-cytometry was performed on paraffin-embedded sections. Mutant p53 prot ein, the bcl-2 oncoprotein and the Ki-67 antigen were detected by immunohis tochemical methods and evaluated quantitatively. WDNEC was more frequently aneuploid than typical carcinoid, had a higher pe rcentage of Ki-67 positive nuclei and presented more frequently the mutant p53 protein. In WDNEC, the mutant p53 (p = 0.001), the bcl-2 oncoprotein (p = 0.002) and the high expression (greater than or equal to 16%) of Ki-67 ( p = 0.0021) were associated with poor prognosis. The prognostic significanc e of mutant p53 and bcl-2 oncoprotein could be confirmed by Cox multiple re gression survival analysis (p = 0.0005). It seems to be advisable to evaluate these features for the management of t he patients affected by WDNEC.