Transforming growth factor beta-1 in rectal tumour, mucosa and plasma in relation to radiotherapy and clinical outcome in rectal cancer patients.
BACKGROUND
Rectal cancer patients are treated with surgery and sometimes radiotherapy. Transforming growth factor-beta1 (TGF-beta1) acts both as an inhibitor of tumour growth and as a promoter of tumour progression. The aim of this study was to determine the levels of TGF-beta1 in tumour tissue, adjacent mucosa and plasma in rectal cancer patients and relate these to the effect of radiotherapy and clinical outcome.


METHODS
One hundred and ten patients scheduled for rectal cancer surgery were included, 49% received pre-operative radiotherapy three-field treatment 5 x 5 Gy. Blood samples and biopsies were taken during surgery and later assayed with enzyme-linked immunosorbent assay for total TGF-beta1 and active TGF-beta1. Patients were then followed for 3 years.


RESULTS
Total and active TGF-beta1 was higher in tumour tissue compared with rectal mucosa (p < 0.0001). Active TGF-beta1 in tumour tissue and rectal mucosa was lower in the irradiated group (p = 0.007; p < 0.0001). Total TGF-beta1 was higher in patients with metastases at primary diagnosis (p = 0.005) compared to patients without. In patients who later developed metastases, the levels of active TGF-beta1 in plasma were lower (p = 0.004). Local recurrence was associated with lower levels of total TGF-beta1 in the rectal mucosa (p = 0.038).


CONCLUSIONS
Higher levels of total TGF-beta1 in tumour tissue at surgery may be indicative of distant metastases, and low levels of active TGF-beta1 in plasma may indicate a risk of developing secondary metastases. Lower levels of total TGF-beta1 in rectal mucosa may influence risk of local recurrence. Measurement of TGF-beta1 in rectal cancer patients may be of clinical use in the future.
Angenete
Eva
E
Department of Surgery, Sahlgrenska University Hospital/Ostra, Göteborg University, 41685, Gothenburg, Sweden. eva.angenete@vgregion.se
Langenskiöld
Marcus
M
Palmgren
Ingrid
I
Falk
Peter
P
Oresland
Tom
T
Ivarsson
Marie-Louise
ML
D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism*; D009362:Neoplasm Metastasis; D012004:Rectal Neoplasms / Q000097:blood* / Q000145:classification / Q000532:radiotherapy* / Q000601:surgery; D053773:Transforming Growth Factor beta1 / Q000097:blood*; D016896:Treatment Outcome
D053773:Transforming Growth Factor beta1