Atypical bronchopulmonary carcinoids show a tendency toward increased apoptotic and proliferative activity

BACKGROUND. Bronchopulmonary carcinoid tumors can be divided into typical a nd atypical carcinoids according to their histologic and clinical features. Atypical carcinoids tend to have less predictable biologic behavior and ar e associated with a worse prognosis than typical carcinoids. The authors ex amined apoptosis and the expression of apoptosis regulating proteins Bcl-2, Bar, Bale, and Mcl-1 in 21 typical and 10 atypical bronchopulmonary carcin oid tumors. To find features distinguishing the growth of these types of tu mors, the expression of p53 protein and the proliferation marker Ki-67 were also investigated. Finally, the parameters were compared with clinical fol low-up data. METHODS. Thirty-one bronchopulmonary carcinoid tumors were examined by usin g in situ 3'-end labeling of DNA (TUNEL) for apoptosis and immunohistochemi cal staining methods for Bcl-2, Bar, Bak, Mcl-1, p53, and Ki-67 in formalin fixed, paraffin embedded tissue specimens. RESULTS. The apoptotic indices (AIs) were low in general (mean 0.18%), but higher AIs (> 0.5%) were observed significantly more often in atypical than in typical carcinoids (P < 0.008) in association with shortened survival ( P ( 0.008). No relation between apoptosis and Bcl-2, Bar, Bak, or Mcl-1 exp ression was found. Expression of p53 protein was detected in only three aty pical carcinoids, which also had significantly higher AIs than p53 negative tumors (P < 0.03). Proliferation rates measured by Ki-67 index were unusua lly low; the highest proliferation rates were observed in atypical carcinoi ds. There was a positive correlation between Al and Ki-67 indices (P < 0.01 ). CONCLUSIONS. This study suggests that the extent of apoptosis in bronchopul monary carcinoid tumors is low. This, together with a low proliferation rat e and an apparent absence of p53 mutation, enables a benign growth pattern. Some atypical carcinoids with enhanced apoptosis are associated with short ened survival, clearly deviating from typical carcinoids. (C) 2000 American Cancer Society.