Analysis of local chronic inflammatory cell infiltrate combined with systemic inflammation improves prognostication in stage II colon cancer independent of standard clinicopathologic criteria.
In Stage II colon cancer, multiple independent studies have shown that a dense intratumoural immune infiltrate (local inflammation) is associated with improved outcomes, while systemic inflammation, measured by various markers, has been associated with poorer outcomes. However, previous studies have not considered the interaction between local and systemic inflammation, nor have they assessed the type of inflammatory response compared with standard clinicopathologic criteria. In order to evaluate the potential clinical utility of inflammatory markers in Stage II colon cancer, we examined local and systemic inflammation in a consecutive series of patients with resected Stage II colon cancer between 2000 and 2010 who were identified from a prospective clinical database. Increased intratumoural chronic inflammatory cell (CIC) density, as assessed by pathologist review of hematoxylin and eosin stained slides, was used to represent local inflammation. Neutrophil-to-lymphocyte ratio (NLR) >5, as calculated from pre-operative full blood counts, was used to represent systemic inflammation. In 396 eligible patients identified, there was a non-significant inverse relationship between local and systemic inflammation. Increased CIC density was significantly associated with improved overall (HR 0.45, p = 0.001) and recurrence-free survival (HR 0.37, p = 0.003). High NLR was significantly associated with poorer overall survival (HR 2.56, p < 0.001). The combination of these markers further stratified prognosis independent of standard high-risk criteria, with a dominant systemic inflammatory response (low CIC/high NLR) associated with the worst outcome (5-year overall survival 55.8%). With further validation this simple, inexpensive combined inflammatory biomarker might assist in patient selection for adjuvant chemotherapy in Stage II colon cancer.
Walter & Eliza Hall Institute of Medical Research, Melbourne, Australia.|Department of Medical Oncology, Royal Melbourne Hospital, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.
Natalie
N
Turner
Walter & Eliza Hall Institute of Medical Research, Melbourne, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.
Hui-Li
HL
Wong
Department of Medical Oncology, Kantonsspital, St Gallen, Switzerland.
Arnoud
A
Templeton
Centre for Translational Pathology, University of Melbourne, Parkville, Australia.
Sagarika
S
Tripathy
Department of Anatomical Pathology, Royal Melbourne Hospital, Parkville, Australia.
Te
T
Whiti Rogers
Department of Colorectal Surgery, Western Health, Footscray, Australia.
Matthew
M
Croxford
Department of Colorectal Surgery, Royal Melbourne Hospital, Parkville, Australia.
Ian
I
Jones
Department of Medical Oncology, Royal Melbourne Hospital, Parkville, Australia.
Mathuranthakan
M
Sinnathamby
Department of Medical Oncology, Royal Melbourne Hospital, Parkville, Australia.
Jayesh
J
Desai
Walter & Eliza Hall Institute of Medical Research, Melbourne, Australia.|Department of Medical Oncology, Royal Melbourne Hospital, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.|Department of Medical Oncology, Western Health, Footscray, Australia.
Jeanne
J
Tie
BioGrid Australia, Melbourne, Australia.
Susie
S
Bae
Centre for Translational Pathology, University of Melbourne, Parkville, Australia.|Department of Anatomical Pathology, Royal Melbourne Hospital, Parkville, Australia.
Michael
M
Christie
Walter & Eliza Hall Institute of Medical Research, Melbourne, Australia.|Department of Medical Oncology, Royal Melbourne Hospital, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.|Department of Medical Oncology, Western Health, Footscray, Australia.|BioGrid Australia, Melbourne, Australia.
Peter
P
Gibbs
Walter & Eliza Hall Institute of Medical Research, Melbourne, Australia.|Department of Medical Oncology, Royal Melbourne Hospital, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.|Department of Medical Oncology, Western Health, Footscray, Australia.
Ben
B
Tran
D000328:Adult; D000368:Aged; D003110:Colonic Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D053843:DNA Mismatch Repair; D005260:Female; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D008214:Lymphocytes / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009504:Neutrophils / Q000473:pathology*; D011379:Prognosis; D011446:Prospective Studies
neutrophil-to-lymphocyte ratio; stage II colon cancer; systemic inflammation; tumour infiltrating lymphocytes