Summary:
Abstract
Purpose The expression of various angiogenic factors was assessed in tumour
samples
of patients with stage III NSCLC before treatment and further analyzed in
relation to
response to Paclitaxel-Ifosfamide-Cisplatin (TIP) chemotherapy.
Methods Freshly isolated lung tumour specimens from 35 NSCLC chemotherapy naive
patients were sampled and analysed for vascular endothelial growth factor
receptor-1
(VEGFR-1), VEGFR-2 and VEGFR-3, Tumor necrosis factor-alpha (TNFa), Tumor
growth factor-beta (TGFb), interleukin-6 (IL6) and IL8, before and after
treatment.
Immunostaining scores were calculated by multiplying the percentage of labeled
cells
by the intensity of staining for each examined parameter.
Results The overall expression of VEGF receptors and particularly of VEGFR1 was
decreased in 68.6% of patients, increased in 22.9% and remained stable in 8.6%
after
the completion of treatment. Similar results were found for VEGFR3 (68.6%
decreased,
25.7% increased and 5.7% stable). For VEGFR2 there was an important increase of
the
value in 65.7% of patients (p<0.01), as the decrease and stable values were
found
similar (17%). There were no statistically important differences for all
immunologic
parameters before and after treatment: TNFa (increase 54.3%, decrease 34.3%,
stable
20%, p-0.28) TGFb (increase 48.6%, decrease 34.3%, stable 17.1%, p-0.13), but no
statistically important differences for IL6 (increase 34.3%, decrease 28.6%,
stable
37.1%, p-0.78) and IL8 (increase 26.5%, decrease 32.4% and stable 41.2%,
p-0.84).
Conclusion Our study identified patterns of angiogenic marker expression with
predictive significance in stage III NSCLC treated with TIP chemotherapy. The
decrease of VEGFR1 and VEGFR3 after treatment it is probably related to the
decrease
of the tumour size, as the increase of VEGFR2 values could be related to high
levels of
precancerous growth factors including VEGF that are released in the circulation
after
chemotherapy something that requires futher investigation.
Keywords:
Non small cell lung carcinoma, Angiogenesis, Immune factors, Cytokines, Chemotherapy
