title: Bronchopulmonary carcinoid: phenotype and long-term outcome in a single-institution series of Italian patients.
abstract: OBJECTIVE
  The histologic distinction between low-grade typical and intermediate-grade atypical bronchopulmonary carcinoids basically lies on cellular differentiation, mitotic activity, and presence of "neoplastic" necrosis; at single patient level, however, none of these features enables a reliable prediction of the clinicopathologic outcome.
  
  
  METHODS
  The long-term postsurgical outcome of a single-institution series of 67 radically treated bronchopulmonary carcinoids was correlated with the tumor phenotype assessed by combining conventional histology with a panel of immunohistochemical markers exploring cell differentiation (chromogranin, NSE, TTF1), cell turnover (Mib1), and apoptosis (Bcl2, Bax).
  
  
  RESULTS
  Fifty-eight (86.6%) carcinoids were assessed as low-grade typical and nine (13.4%) were assessed as intermediate-grade atypical. The mean follow-up was of 85.13 months (range, 28-168; median, 82.0). All cases expressed neuroendocrine markers, whereas TTF1 was never expressed. At univariate analysis, tumor recurrence (n = 6) correlated significantly with the carcinoid histotype (P = 0.002) and with each of the following variables: tumor location (P = 0.01), mitotic index (P = 0.003), necrosis (P = 0.002), tumor vascular invasion (P = 0.0001), Mib1 expression (P = 0.005), Bcl2 expression (P = 0.024), and synchronous node metastasis (P = 0.028). The best cutoffs for Mib1 and Bcl2 expression (calculated by receiver operating characteristic curves) discriminating recurrent versus nonrecurrent tumors were 5.4% for Mib1 and 2.0% for Bcl2 (Mib1: sensitivity, 83%; specificity, 97%; area under curve, 0.844 +/- 0.14; Bcl2: sensitivity, 83%; specificity, 65%; area under curve, 0.769 +/- 0.12). By stratifying the patients according to the obtained cutoffs, significant differences emerged in the patients' disease-free survival (log-rank test: Mib1, P = 0.0001; Bcl2, P = 0.01).
  
  
  CONCLUSIONS
  Mib1 and Bcl2 significantly discriminate between recurrent versus nonrecurrent tumors, producing a biologically plausible, diagnostically suitable immunohistochemical pattern.
authors.affiliation: Department of Medical Diagnostic Sciences and Special Therapies, University of Padova, Italy. massimo.rugge@unipd.it
authors.forename: Massimo
authors.initials: M
authors.lastname: Rugge
authors.forename: Matteo
authors.initials: M
authors.lastname: Fassan
authors.forename: Roberto
authors.initials: R
authors.lastname: Clemente
authors.forename: Giovanna
authors.initials: G
authors.lastname: Rizzardi
authors.forename: Luciano
authors.initials: L
authors.lastname: Giacomelli
authors.forename: Gianmaria
authors.initials: G
authors.lastname: Pennelli
authors.forename: Claudia
authors.initials: C
authors.lastname: Mescoli
authors.forename: Daniela
authors.initials: D
authors.lastname: Segat
authors.forename: Federico
authors.initials: F
authors.lastname: Rea
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002276:Carcinoid Tumor / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D002648:Child; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007558:Italy; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D010641:Phenotype; D011379:Prognosis; D012142:Respiratory Tract Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D013995:Time; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor