Alessandro Del Gobbo1, Nicola Fusco1,2, Marco Barella1,3, Giulia Ercoli1, Amedeo Sciarra1, Alessandro Palleschi4, Fabio Pagni5, Caterina Marchiò6, Mauro Papotti7, Stefano Ferrero8,9. 1. Division of Pathology, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University of Milan, Via Francesco Sforza 35, 20122, Milan, Italy. 2. Department of Biomedical, Surgical, and Dental Sciences, University of Milan, Milan, Italy. 3. School of Medicine, University of Milan, Milan, Italy. 4. Department of Thoracic Surgery, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, Italy. 5. Department of Medicine and Surgery, University of Milan-Bicocca, Monza, Italy. 6. Department of Medical Sciences, University of Turin, Pathology Unit, Città della Salute e della Scienza di Torino, Turin, Italy. 7. Department of Oncology, University of Turin, Pathology Unit, Città della Salute e della Scienza di Torino, Turin, Italy. 8. Division of Pathology, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University of Milan, Via Francesco Sforza 35, 20122, Milan, Italy. stefano.ferrero@unimi.it. 9. Department of Biomedical, Surgical, and Dental Sciences, University of Milan, Milan, Italy. stefano.ferrero@unimi.it.
Abstract
PURPOSE: Neuroendocrine tumors of the lung (LNETs) encompass a heterogeneous group of lesions, including tumors with no or low metastatic potential, such as typical (TCs) and atypical (ACs) carcinoids, and highly aggressive neuroendocrine carcinomas. To date, only a few biomarkers with prognostic impact have been identified in LNETs. Previous experimental studies have suggested that the cytokine CXCL12 might have a role in stratifying the outcome of lung cancer as well as LNET patients. However, the reliability of immunohistochemical (IHC) tissue expression of CXCL12 in evaluating the prognosis of resected LNETs is currently not known. METHODS: Here, we subjected a cohort of 112 resected LNETs specifically enriched for ACs to IHC for CXCL12 and Ki67 using routine procedures. The clinical value of CXCL12 was assessed by applying the Cox proportional-hazards model to overall and disease-free survival rates. RESULTS: We found that CXCL12 was expressed in 8.3 to 38% of LNETs, depending on the different diagnostic categories. Upon survival analysis, when considering the whole cohort, we found that CXCL12-positive cases exhibited shorter disease-free survival rates compared to CXCL12-negative cases. Among ACs, tumors overexpressing CXCL12 showed significantly shorter disease-free survival rates. Finally, we found that the Ki67 index in ACs was higher in the CXCL12-positive cases. CONCLUSION: CXCL12 immunohistochemistry may serve as a potentially useful tool to better stratify LNETs, and more specifically ACs, in clinical practice.
PURPOSE:Neuroendocrine tumors of the lung (LNETs) encompass a heterogeneous group of lesions, including tumors with no or low metastatic potential, such as typical (TCs) and atypical (ACs) carcinoids, and highly aggressive neuroendocrine carcinomas. To date, only a few biomarkers with prognostic impact have been identified in LNETs. Previous experimental studies have suggested that the cytokine CXCL12 might have a role in stratifying the outcome of lung cancer as well as LNET patients. However, the reliability of immunohistochemical (IHC) tissue expression of CXCL12 in evaluating the prognosis of resected LNETs is currently not known. METHODS: Here, we subjected a cohort of 112 resected LNETs specifically enriched for ACs to IHC for CXCL12 and Ki67 using routine procedures. The clinical value of CXCL12 was assessed by applying the Cox proportional-hazards model to overall and disease-free survival rates. RESULTS: We found that CXCL12 was expressed in 8.3 to 38% of LNETs, depending on the different diagnostic categories. Upon survival analysis, when considering the whole cohort, we found that CXCL12-positive cases exhibited shorter disease-free survival rates compared to CXCL12-negative cases. Among ACs, tumors overexpressing CXCL12 showed significantly shorter disease-free survival rates. Finally, we found that the Ki67 index in ACs was higher in the CXCL12-positive cases. CONCLUSION:CXCL12 immunohistochemistry may serve as a potentially useful tool to better stratify LNETs, and more specifically ACs, in clinical practice.
Authors: William D Travis; Elisabeth Brambilla; Allen P Burke; Alexander Marx; Andrew G Nicholson Journal: J Thorac Oncol Date: 2015-09 Impact factor: 15.609