TY - JOUR
T1 - A Multimodal Biomarker Predicts Dissemination of Bronchial Carcinoid
AU - Reuling, Ellen M. B. P.
AU - Naves, Dwayne D.
AU - Kortman, Pim C.
AU - Broeckaert, Mark A. M.
AU - Plaisier, Peter W.
AU - Dickhoff, Chris
AU - Daniels, Johannes M. A.
AU - Radonic, Teodora
N1 - Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/7/1
Y1 - 2022/7/1
N2 - Background: Curatively treated bronchial carcinoid tumors have a relatively low metastatic potential. Gradation into typical (TC) and atypical carcinoid (AC) is limited in terms of prognostic value, resulting in yearly follow-up of all patients. We examined the additional prognostic value of novel immunohistochemical (IHC) markers to current gradation of carcinoids. Methods: A retro-spective single-institution cohort study was performed on 171 patients with pathologically diagnosed bronchial carcinoid (median follow-up: 66 months). The risk of developing distant metastases based on histopathological characteristics (Ki-67, p16, Rb, OTP, CD44, and tumor diameter) was evaluated using multivariate regression analysis and the Kaplan–Meier method. Results: Of 171 pa-tients, seven (4%) had disseminated disease at presentation, and 164 (96%) received curative-intent treatment with either endobronchial treatment (EBT) (n = 61, 36%) or surgery (n = 103, 60%). Among the 164 patients, 13 developed metastases at follow-up of 81 months (IQR 45–162). Univariate analysis showed that Ki-67, mitotic index, OTP, CD44, and tumor diameter were associated with development of distant metastases. Multivariate analysis showed that mitotic count, Ki-67, and OTP were independent risk factors for development of distant metastases. Using a 5% cutoff for Ki-67, Kaplan–Meier analysis showed that the risk of distant metastasis development was significantly associated with the number of risk predictors (AC, Ki-67 ≥ 5%, and loss of OTP or CD44) (p < 0.0001). Six out of seven patients (86%) with all three positive risk factors developed distant metastasis. Con-clusion: Mitotic count, proliferation index, and OTP IHC were independent predictors of dissemination at follow-up. In addition to the widely used carcinoid classification, a comprehensive analysis of histopathological variables including Ki-67, OTP, and CD44 could assist in the determi-nation of distant metastasis risks of bronchial carcinoids.
AB - Background: Curatively treated bronchial carcinoid tumors have a relatively low metastatic potential. Gradation into typical (TC) and atypical carcinoid (AC) is limited in terms of prognostic value, resulting in yearly follow-up of all patients. We examined the additional prognostic value of novel immunohistochemical (IHC) markers to current gradation of carcinoids. Methods: A retro-spective single-institution cohort study was performed on 171 patients with pathologically diagnosed bronchial carcinoid (median follow-up: 66 months). The risk of developing distant metastases based on histopathological characteristics (Ki-67, p16, Rb, OTP, CD44, and tumor diameter) was evaluated using multivariate regression analysis and the Kaplan–Meier method. Results: Of 171 pa-tients, seven (4%) had disseminated disease at presentation, and 164 (96%) received curative-intent treatment with either endobronchial treatment (EBT) (n = 61, 36%) or surgery (n = 103, 60%). Among the 164 patients, 13 developed metastases at follow-up of 81 months (IQR 45–162). Univariate analysis showed that Ki-67, mitotic index, OTP, CD44, and tumor diameter were associated with development of distant metastases. Multivariate analysis showed that mitotic count, Ki-67, and OTP were independent risk factors for development of distant metastases. Using a 5% cutoff for Ki-67, Kaplan–Meier analysis showed that the risk of distant metastasis development was significantly associated with the number of risk predictors (AC, Ki-67 ≥ 5%, and loss of OTP or CD44) (p < 0.0001). Six out of seven patients (86%) with all three positive risk factors developed distant metastasis. Con-clusion: Mitotic count, proliferation index, and OTP IHC were independent predictors of dissemination at follow-up. In addition to the widely used carcinoid classification, a comprehensive analysis of histopathological variables including Ki-67, OTP, and CD44 could assist in the determi-nation of distant metastasis risks of bronchial carcinoids.
KW - Ki-67
KW - distant metastases
KW - immunohistochemistry
KW - prognosis
KW - pulmonary carcinoid
UR - http://www.scopus.com/inward/record.url?scp=85133133756&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/cancers14133234
DO - https://doi.org/10.3390/cancers14133234
M3 - Review article
C2 - 35805004
SN - 2072-6694
VL - 14
JO - Cancers
JF - Cancers
IS - 13
M1 - 3234
ER -