Evaluation of CTLA-4 expression and relevance as a novel prognostic factor in patients with non-small cell lung cancer.
The role of CTLA-4 in negative regulation of T-cell mediated immune response is particularly well established. Much less is known about its expression and function in tumour cells, and to our knowledge, no data are available on its possible impact on prognosis of NSCLC patients. We investigated CTLA-4 expression and prognostic role in 81 patients with radically resected stage I-III NSCLC. The analysis was performed by tissue microarray immunohistochemistry, and the median H-score of 20 was used as a threshold to define CTLA-4 overexpressing tumours. Correlation with standard prognostic factors was performed by using absolute and relative fold change indexes. Hazard ratios (HR) and corresponding 95% confidence limits (95% CL) were computed through the Cox model. A higher frequency of CTLA-4 overexpression (>20) was found in non-squamous than in squamous NSCLC (52.8 vs. 35.7%) and in Ki67 ≤ 15 expressing tumours, as compared to those with Ki67 > 15 (51.5 vs. 38.7%). A reduced death rate was found in CTLA-4 overexpressing tumours (HR = 0.60, 95% CL = 0.28/1.23), and a further decrease was observed when considering tumours with CTLA-4 > 20 and Ki67 ≤ 15, in comparison with tumours with CTLA-4 ≤ 20 and Ki67 > 15 (HR = 0.41; 95% CL = 0.15/1.13). Our observational and exploratory study provides a first and promising indication for an independent prognostic effect of CTLA-4 overexpression in radically resected NSCLC. We presume that this effect relies on modulation of the interaction of microscopic disease with CTLA-4-ligands expressing cells leading to NSCLC cell death.
Department of Pathology, IRCCS AOU San Martino-IST, Genoa, Italy.
Sandra
S
Salvi
Vincenzo
V
Fontana
Simona
S
Boccardo
Domenico Franco
DF
Merlo
Edoardo
E
Margallo
Stefania
S
Laurent
Anna
A
Morabito
Erika
E
Rijavec
Maria Giovanna
MG
Dal Bello
Marco
M
Mora
Giovanni Battista
GB
Ratto
Francesco
F
Grossi
Mauro
M
Truini
Maria Pia
MP
Pistillo
D000368:Aged; D000369:Aged, 80 and over; D060908:CTLA-4 Antigen / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D016019:Survival Analysis
D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human