PROLIFERATION MARKERS MIB-1 AND PCNA IN PULMONARY NEUROENDOCRINE TUMORS

We examined cell proliferation in 40 pulmonary neuroendocrine tumors ( 17 typical carcinoid tumors [TC], 7 atypical carcinoid tumors [ATC], 5 large cell neuroendocrine carcinomas [LCNEC] and 11 small cell carcin omas [SCC], using the monoclonal antibody MIB-1 detecting the Ki-67 an tigen and anti-proliferating cell nuclear antigen (PCNA) as immunochem ical markers of cell proliferation, to seek correlation with tumor typ e, mitotic index, stage, and disease outcome. MIB-1 and anti-PCNA immu nostaining was performed on formalin-fixed, paraffin-embedded tissue. Mean MIB-1 and PCNA proliferation indices were 4.4 and 11.6% for TC, 1 4.1 and 23.7% for ATC, 35.9 and 72.0% for LCNEC, and 36.2 and 54.6% fo r SCC. With both MIB-1 and anti-PCNA proliferation indices, there were statistically significant differences between TC or ATC and LCNEC or SCC, but not between TC and ATC or LCNEC and SCC. Correlation of proli feration index and mitotic index was strong for anti-PCNA (r = 0.82), but weaker for MIB-1 (r = 0.58). The MIB-1 index correlated with stage (p < 0.0003), differentiating stages I-III from stage IV. The PCNA in dex weakly correlated with stage (p < 0.36), differentiating between s tages I and III. A high MIB-1 index strongly correlated with a poor ou tcome (p < 0.0001), but a low MIB-1 index was not predictive of a unif ormly favorable outcome (2 cases of TC with a low MIB-1 index had a po or outcome). Analysis by Cox proportional hazards regression model sho wed that traditional histologic classification was the best predictor of outcome. We conclude that MIB-1 and anti-PCNA proliferation indices correlate with tumor type, mitotic index, stage, and disease outcome, but proliferation markers do not add prognostic information beyond th at provided by traditional histologic tumor classification and staging of pulmonary neuroendocrine tumors.