Ki-67 Index of 55% Distinguishes Two Groups of Bronchopulmonary Pure and Composite Large Cell Neuroendocrine Carcinomas with Distinct Prognosis
| Autor: | Andrea Tironi, Ugo Pastorino, Giovanni Centonze, Alfredo Berruti, Giancarlo Pruneri, Elisa Roca, Adele Busico, Giovanna Garzone, Stefano Ferrero, Massimo Milione, Luisa Bercich, Patrick Maisonneuve, Federica Grillo, Alessio Pellegrinelli, Paola Bossi, Ketevani Kankava, Luigi Rolli, Carlo Capella, Laura Cattaneo, Sara Pusceddu, Alessandro Mangogna, Mauro Roberto Benvenuti, Paola Spaggiari, Maria Sole Gallazzi, Rosalia Romano, Alessandro Del Gobbo, Natalie Prinzi |
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| Přispěvatelé: | Milione, M., Maisonneuve, P., Grillo, F., Mangogna, A., Centonze, G., Prinzi, N., Pusceddu, S., Garzone, G., Cattaneo, L., Busico, A., Bossi, P., Spaggiari, P., Pellegrinelli, A., Del Gobbo, A., Ferrero, S., Kankava, K., Pruneri, G., Rolli, L., Roca, E., Bercich, L., Tironi, A., Benvenuti, M. R., Gallazzi, M. S., Romano, R., Berruti, A., Pastorino, U., Capella, C. |
| Rok vydání: | 2020 |
| Předmět: |
Combined large cell neuroendocrine carcinoma
Ki-67 index Large cell neuroendocrine carcinoma Napsin A medicine.medical_specialty Lung Neoplasms Proliferation index Endocrinology Diabetes and Metabolism 030209 endocrinology & metabolism Biology medicine.disease_cause Gastroenterology 030218 nuclear medicine & medical imaging 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Endocrinology Internal medicine medicine Humans Endocrine and Autonomic Systems Large cell CD44 medicine.disease Prognosis Survival Analysis Neuroendocrine Carcinomas Carcinoma Neuroendocrine Ki-67 Antigen Ki-67 biology.protein Adenocarcinoma Immunohistochemistry Carcinoma Large Cell KRAS |
| Zdroj: | Neuroendocrinology. 111(5) |
| ISSN: | 1423-0194 |
| Popis: | Background: Little information is available concerning prognostic factors for bronchopulmonary large cell neuroendocrine carcinomas (BP-LCNECs) and even less is known about combined LCNECs (Co-LCNECs). We investigated whether an integrated morphological, immunohistochemical, and molecular approach could be used for their prognostic evaluation. Methods: Morphological (including combined features), proliferative (mitotic count/Ki-67 index), immunohistochemical (napsin A, p40, TTF-1, CD44, OTP, SSTR2A, SSTR5, mASH1, p53, RB1, and MDM2), and genomic (TP53, RB1, ATM, JAK2, KRAS, and STK11) findings were analyzed in BP-LCNECs from 5 Italian centers, and correlated with overall survival (OS). The Ki-67 index was expressed as the percentage of positive cells in hot spots as indicated in the WHO 2019 Digestive System Tumors and, for Co-LCNECs, the Ki-67 index was evaluated only in the LCNEC component. Results: A total of 111 LCNECs were distinguished into 70 pure LCNECs, 35 Co-LCNECs (27 with adenocarcinoma [ADC] and 8 with squamous cell carcinoma [SqCC]), and 6 LCNECs with only napsin A immunoreactivity. The Ki-67 index cutoff at 55% evaluated in the neuroendocrine component was the most powerful predictor of OS (log-rank p = 0.0001) in all LCNECs; 34 cases had a Ki-67 index p = 0.0001) were also observed between pure and Co-LCNECs. A significant difference in OS was found between pure LCNECs-A and Co-LCNECs-A (p < 0.05) but not between pure LCNECs-B and Co-LCNECs-B. Co-LCNEC-ADC and LCNEC napsin A+ cases had longer OS than pure LCNEC and Co-LCNEC-SqCC cases (log-rank p = 0.0001). On multivariable analysis, tumor location, pure versus combined features, and napsin A, but no single gene mutation, were significantly associated with OS after adjustment for Ki-67 index and study center (p < 0.05). Conclusions: The Ki-67 proliferation index and the morphological characterization of combined features in LCNECs seem to be important tools for predicting clinical outcome in BP-LCNECs. |
| Databáze: | OpenAIRE |
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