Partitioning of bronchopulmonary carcinoids in two different prognostic categories by Ki-67 score

Introduction: Histological distinction between typical and atypical bronchopulmonary car- cinoids is based on mitotic activity and necrosis. Regardless of these two parameters, outcome after surgery is often unpredictable. In this study the prognostic value of different clinico-pathological factors was retrospectively analyzed in a large series of patients with bronchopulmonary carcinoid. Materials and Methods: The long-term post-surgical out- come of 106 radically treated patients affected by bronchopulmonary carcinoid from two Italian centers was correlated with tumor characteristics assessed by combining conven- tional histology with a panel of immunohistochemical markers of neuroendocrine differen- tiation (chromogranin-A, NSE) and proliferation activity (Ki-67 score). Results: Carcinoids were assessed as typical (TC = 75; 70.8%) and atypical (AC = 31; 29.2%). Mean follow-up was 8.3 years (range: 0-20; median: 8.0). All cases expressed neuroendocrine markers. At univariate analysis, tumor recurrence [14/75 TC (18.7%), 15/31 AC (48.4%)] correlated with carcinoid histotype (P = 0.003), tumor size (P = 0.012), mitotic index (P = 0.044), Ki-67 score (P < 0.0001), and synchronous node metastasis (P = 0.037). Of these, Cox multivari- ate analysis confirmed only Ki-67 score as independent predictor of disease recurrence (P = 0.009). The best cut-off for Ki-67 score (calculated by ROC curves) discriminating recurrent vs non-recurrent disease was 4% (sensitivity 79.3%; specificity 83.8%; area under the curve 0.85). By stratifying patients according to this cut-off, a significantly dif- ferent disease-free survival was found (log-rank test P < 0.0001). Conclusion: Ki-67 score accurately separates bronchopulmonary carcinoids in two well-distinct histo-prognostic categories. Ki-67 score predicts the patients outcome better than mitotic count, histotype, and tumor stage and it is therefore helpful in establishing the appropriate follow-up. © 2011 Grimaldi, Muser, Beltrami, Machin, Morelli, Pizzolitto, Talmassons, Marciello, Colao, Monaco, Monaco and Faggiano

Non-small cell lung carcinoma: morphology and DNA content

Objective: To correlate stage-related and histologic features of non-small cell lung cancer (NSCLC) with DNA flow cytometric parameters. Study design: The clinicopathologic features, DNA flow cytometric parameters (ploidy type, S-phase fraction and DNA index [DI]) of 72 surgically resected NSCLC were reviewed. Results: NSCLC were classified on the basis of their DI in diploid, peridiploid, hypotriploid, triploid, hypertriploid, tetraploid, hypertetraploid and multiploid tumors. DI was significantly related to pleural infiltration, pT, histologic type and evidence of necrosis. Tumors infiltrating the pleura were mostly triploid or hypertriploid; high pT stages were also hypertetraploid. Adenocarcinomas showed a wide DI distribution, squamous carcinomas were mostly diploid, triploid or hypertriploid and large cell carcinomas were mostly triploid, hypertriploid and hypertetraploid. The best combination of features able to predict disease relapse was pT plus pN plus grading and divergent differentiation. Conclusion: Many stage-related and histologic features are associated with particular DI classes, which vary in relation to the feature itself and, in some cases, regardless of classical methods of grading and histologic typing. DNA content analysis highlights greater biologic heterogeneity in NSCLC than evidenced morphologically

Partitioning of bronchopulmonary carcinoids in twodifferent prognostic categories by Ki-67 score

Introduction: Histological distinction between typical and atypical bronchopulmonary carcinoids is based on mitotic activity and necrosis. Regardless of these two parameters, outcome after surgery is often unpredictable. In this study the prognostic value of different clinico-pathological factors was retrospectively analyzed in a large series of patients with bronchopulmonary carcinoid. Patients and Methods:The long-term post-surgical outcome of 106 radically treated patients affected by bronchopulmonary carcinoid from two Italian centers was correlated with tumor characteristics assessed by combining conventional histology with a panel of immunohistochemical markers of neuroendocrine differentiation (chromogranin-A, NSE) and proliferation activity (Ki-67 score). Results: Carcinoids were assessed as typical (TC=75; 70.8%) and atypical (AC=31; 29.2%). Mean follow-up was 8.3 years (range: 0–20; median: 8.0). All cases expressed neuroendocrine markers. At univariate analysis, tumor recurrence [14/75 TC (18.7%), 15/31 AC (48.4%)] correlated with carcinoid histotype (P =0.003), tumor size (P =0.012), mitotic index (P =0.044), Ki-67 score (P <0.0001), and synchronous node metastasis (P =0.037). Of these, Cox multivariate analysis confirmed only Ki-67 score as independent predictor of disease recurrence (P =0.009).The best cut-off for Ki-67 score (calculated by ROC curves) discriminating recurrent vs non-recurrent diseasewas 4% (sensitivity 79.3%; specificity 83.8%; area under the curve 0.85). By stratifying patients according to this cut-off, a significantly different diseasefree survival was found (log-rank test P <0.0001). Conclusion: Ki-67 score accurately separates bronchopulmonary carcinoids in two well-distinct histo-prognostic categories. Ki-67 score predicts the patients outcome better than mitotic count, histotype, and tumor stage and it is therefore helpful in establishing the appropriate follow-up