Analysis of NSCLC tumour heterogeneity, proliferative and 18F-FDG PET indices reveals Ki67 prognostic role in adenocarcinomas.
OBJECTIVE
The role of tumour metabolic and proliferative indices in predicting non-small-cell lung cancer (NSCLC) patients' prognosis is unclear. We correlated fluorine 18 ((18) F)-fluorodeoxyglucose (FDG)-positron emission tomography (PET) value and Ki67 index to patients' survival, taking into account tumour heterogeneity, disease characteristics and genetic aberrations.


RESULTS
A series of 383 NSCLCs was arranged into tissue microarrays and Ki67 staining was analysed by immunohistochemistry. The maximum standardized uptake (SUV(MAX) ) value detected by (18) F-FDG-PET analysis was calculated over a region of interest. Large-cell and squamous cell carcinomas had higher proliferative and metabolic activities than adenocarcinomas, and the two measures were correlated significantly. The hot-spot Ki67 value was correlated with patients' survival and the cut-off to discriminate patients in the survival risk groups was 20%. Ki67 hot-spot values were greater in anaplastic lymphoma kinase (ALK) rearranged tumours. Adenocarcinomas showed the highest intratumour heterogeneity in proliferative activity and the hot-spot Ki67 value predicted only the prognosis of patients in this group. Although tumour metabolic activity was not associated with patients' prognosis, a SUV(MAX) > 2 was related to nodal metastases, tumour size and grade.


CONCLUSIONS
Our results highlight how tumour heterogeneity influences evaluation of prognostic biomarkers. Our data support Ki67 evaluation to estimate NSCLC patients' prognosis, particularly for adenocarcinoma.
Division of Pathology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
Alessandro
http://orcid.org/0000-0002-8194-3232
A
Del Gobbo
Division of Pathology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.|Department of Pathophysiology and Organ Transplantation, University of Milan, Milan, Italy.
Alessio
A
Pellegrinelli
Division of Pathology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.|Department of Pathophysiology and Organ Transplantation, University of Milan, Milan, Italy.
Gabriella
G
Gaudioso
Division of Nuclear Medicine, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
Massimo
M
Castellani
Struttura Complessa di Anatomia Patologica, Istituto Nazionale Tumori, Fondazione G. Pascale, Naples, Italy.
Federica
F
Zito Marino
Struttura Complessa di Anatomia Patologica, Istituto Nazionale Tumori, Fondazione G. Pascale, Naples, Italy.
Renato
R
Franco
Division of Thoracic Surgery, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
Alessandro
A
Palleschi
Division of Thoracic Surgery, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
Mario
M
Nosotti
Division of Pathology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.|Department of Pathophysiology and Organ Transplantation, University of Milan, Milan, Italy.
Silvano
S
Bosari
Division of Pathology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.|Istituto Nazionale Genetica Molecolare 'Romeo ed Enrica Invernizzi', Milan, Italy.
Valentina
V
Vaira
Division of Pathology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.|Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
Stefano
S
Ferrero
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D000368:Aged; D018287:Carcinoma, Large Cell; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008175:Lung Neoplasms; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011379:Prognosis; D019275:Radiopharmaceuticals
D019394:Ki-67 Antigen; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
Ki67; PET; adenocarcinoma; lung cancer