TY - JOUR
T1 - Most high-grade neuroendocrine tumours of the lung are likely to secondarily develop from pre-existing carcinoids
T2 - innovative findings skipping the current pathogenesis paradigm
AU - Pelosi, Giuseppe
AU - Bianchi, Fabrizio
AU - Dama, Elisa
AU - Simbolo, Michele
AU - Mafficini, Andrea
AU - Sonzogni, Angelica
AU - Pilotto, Sara
AU - Harari, Sergio
AU - Papotti, Mauro
AU - Volante, Marco
AU - Fontanini, Gabriella
AU - Mastracci, Luca
AU - Albini, Adriana
AU - Bria, Emilio
AU - Calabrese, Fiorella
AU - Scarpa, Aldo
PY - 2018/4/1
Y1 - 2018/4/1
N2 - Among lung neuroendocrine tumours (Lung-NETs), typical carcinoid (TC) and atypical carcinoid (AC) are considered separate entities as opposed to large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC). By means of two-way clustering analysis of previously reported next-generation sequencing data on 148 surgically resected Lung-NETs, six histology-independent clusters (C1 → C6) accounting for 68% of tumours were identified. Low-grade Lung-NETs were likely to evolve into high-grade tumours following two smoke-related paths. Tumour composition of the first path (C5 → C1 → C6) was coherent with the hypothesis of an evolution of TC to LCNEC, even with a conversion of SCLC-featuring tumours to LCNEC. The second path (C4 → C2–C3) had a tumour composition supporting the evolution of AC to SCLC-featuring tumours. The relevant Ki-67 labelling index varied accordingly, with median values being 5%, 9% and 50% in the cluster sequence C5 → C1 → C6, 12% in cluster C4 and 50–60% in cluster C2–C3. This proof-of-concept study suggests an innovative view on the progression of pre-existing TC or AC to high-grade NE carcinomas in most Lung-NET instances.
AB - Among lung neuroendocrine tumours (Lung-NETs), typical carcinoid (TC) and atypical carcinoid (AC) are considered separate entities as opposed to large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC). By means of two-way clustering analysis of previously reported next-generation sequencing data on 148 surgically resected Lung-NETs, six histology-independent clusters (C1 → C6) accounting for 68% of tumours were identified. Low-grade Lung-NETs were likely to evolve into high-grade tumours following two smoke-related paths. Tumour composition of the first path (C5 → C1 → C6) was coherent with the hypothesis of an evolution of TC to LCNEC, even with a conversion of SCLC-featuring tumours to LCNEC. The second path (C4 → C2–C3) had a tumour composition supporting the evolution of AC to SCLC-featuring tumours. The relevant Ki-67 labelling index varied accordingly, with median values being 5%, 9% and 50% in the cluster sequence C5 → C1 → C6, 12% in cluster C4 and 50–60% in cluster C2–C3. This proof-of-concept study suggests an innovative view on the progression of pre-existing TC or AC to high-grade NE carcinomas in most Lung-NET instances.
KW - Cluster analysis
KW - Lung
KW - Neuroendocrine
KW - Transition
KW - Tumours
UR - http://www.scopus.com/inward/record.url?scp=85044049224&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85044049224&partnerID=8YFLogxK
U2 - 10.1007/s00428-018-2307-3
DO - 10.1007/s00428-018-2307-3
M3 - Article
C2 - 29388013
AN - SCOPUS:85044049224
VL - 472
SP - 567
EP - 577
JO - Virchows Archiv - A Pathological Anatomy and Histopathology
JF - Virchows Archiv - A Pathological Anatomy and Histopathology
SN - 0945-6317
IS - 4
ER -