Tumour necrosis factor-alpha expression in tumour islets confers a survival advantage in non-small cell lung cancer.
BACKGROUND
The role of TNFalpha in cancer is complex with both pro-tumourigenic and anti-tumourigenic roles proposed. We hypothesised that anatomical microlocalisation is critical for its function.


METHODS
This study used immunohistochemistry to investigate the expression of TNFalpha in the tumour islets and stroma with respect to survival in 133 patients with surgically resected NSCLC.


RESULTS
TNFalpha expression was increased in the tumour islets of patients with above median survival (AMS) compared to those with below median survival (BMS)(p = 0.006), but similar in the stroma of both groups. Increasing tumour islet TNFalpha density was a favorable independent prognostic indicator (p = 0.048) while stromal TNFalpha density was an independent predictor of reduced survival (p = 0.007). Patients with high TNFalpha expression (upper tertile) had a significantly higher 5-year survival compared to patients in the lower tertile (43% versus 22%, p = 0.01). In patients with AMS, 100% of TNFalpha+ cells were macrophages and mast cells, compared to only 28% in the islets and 50% in the stroma of BMS patients (p < 0.001).


CONCLUSIONS
The expression of TNFalpha in the tumour islets of patients with NSCLC is associated with improved survival suggesting a role in the host anti-tumour immunological response. The expression of TNFalpha by macrophages and mast cells is critical for this relationship.
Ohri
Chandra M
CM
Institute for Lung Health, Glenfield Hospital, Leicester, UK. cohri@doctors.org.uk
Shikotra
Aarti
A
Green
Ruth H
RH
Waller
David A
DA
Bradding
Peter
P
D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018287:Carcinoma, Large Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D011379:Prognosis; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D014409:Tumor Necrosis Factor-alpha