Ki-67 Evaluation for Clinical Decision in Metastatic Lung Carcinoids: A Proof of Concept

Accrual of metastatic pulmonary carcinoid patients for therapy is usually relied on clinical and histologic characterization, with no role for the proliferation activity as defined by Ki-67 labelling index (LI). A total of 14 carcinoid patients with tumour primaries (TP) and 19 corresponding tumour metastases (TM) were blindly reviewed by 2 different pathologists for necrosis, mitotic count, and Ki-67 LI. Ki-67 LI outperformed histologic subtyping, mitotic count, and necrosis with good to almost excellent (0.40-0.75) inter-observer agreement. About 10% cut-off Ki-67 LI predicted survival better than histology for TP and TM for both observers. The TM patients survived differently according to diverse treatments (somatostatin analogues [SSAs], analogues plus additional treatments except for platinum; platinum-based chemotherapy) in close correlation with <10%, 10% to 20%, and >20% cut-off thresholds of Ki-67 LI, respectively. There was also a trend for an increase in Ki-67 LI in TM as compared with TP. This is the first proof of concept in which a clinical potential is preliminarily suggested for Ki-67 LI to better stratify pulmonary metastatic carcinoid patients for treatment according to a criterion of histology-independent biological aggressiveness.