Mast cells correlate with angiogenesis and poor outcome in stage I lung adenocarcinoma

Abstract

Angiogenesis is in part related to mast cells. However, the biological significance of mast cells within lung carcinoma remains unclear. Immunohistochemistry was used to stain for tryptase, CD34 and vascular endothelial growth factor (VEGF) in 85 cases of stage I nonsmall cell lung carcinoma. VEGF was found in 33 of 53 adenocarcinomas and 14 of 32 squamous cell carcinomas. Cases of adenocarcinoma had significantly higher mast cell counts than those of squamous cell carcinoma. In adenocarcinoma, mast cell counts in VEGF‐positive tumours were significantly higher than in VEGF‐negative tumours, whereas in squamous cell carcinoma they were not. Good correlation was observed between intratumoural mast cell counts and microvessel counts. Double staining showed most intratumoural mast cells expressed VEGF. Importantly, only in lung adenocarcinoma, members in the high mast cell count group had significantly worse prognosis than those in the low mast cell count group. It is concluded that tumour‐released vascular endothelial growth factors may be related to mast cell accumulation, intratumoural mast cells may produce vascular endothelial growth factor, and stromal mast cells correlate with angiogenesis and poor outcome in stage I lung adenocarcinoma.

Smoker and non-smoker lung adenocarcinoma is characterized by distinct tumor immune microenvironments

“…Regarding the impact of mast cells on lung cancer patient outcomes, both adverse and favorable, several contradictory reports have been published. 24,25 This is perhaps due to the mixture of resting and activated mast cells in the previous studies. Interestingly, when resting and activated mast cells were combined together, they were significantly correlated with prolonged survival of NSCLC patients (Figure S3).…”

Thymidine phosphorylase and vascular endothelial growth factor in patients with Stage I lung adenocarcinoma

“…It has been reported that intratumoral macrophages express TP in human malignancies 14,15,[17][18][19] and that activated mast cells express TP in atherosclerotic plaques. 25 Activated mast cells also express VEGF 27 and bFGF. 34 Distinct patterns of TP expression have been observed in human malignancies of various organs.…”

“…The association of tumor cell-VEGF expression with increased MVCs and poor clinical outcome in patients with NSCLC has been reported, supporting the clinical significance of VEGF as an important angiogenic factor and prognostic factor in NSCLC. 3,4,27,30 There has been no report on the broad expression of VEGF in tumor-associated stromal cells of NSCLC, although broad expression of TP and bFGF has been found in tumor-associated stromal cells of NSCLC. 24,31 The clinical significance of TP and bFGF as angiogenic factors and/or prognostic factors for NSCLC is still debated.…”

“…25 Angiogenic factors, including TP, stimulate mast cell migration in vitro. 26 Recent investigations [27][28][29] have demonstrated that mast cell accumulation is associated with tumor angiogenesis and poor outcome in patients with NSCLC, and especially in patients with adenocarcinoma of the lung. Vascular endothelial growth factor (VEGF) expression in tumor cells is associated with increased MVCs and a poor prognosis in patients with NSCLC, supporting the role VEGF as a mitogenic growth factor that is selective for vascular endothelial cells and as an important prognostic factor.…”

Role of infiltrated leucocytes in tumour growth and spread

“…An infiltration of mast cells has been found in a variety of human cancers, including non-small-cell lung cancer (Shijubo et al, 2003), breast cancer (Kankkunen et al, 1997), colorectal cancer (Lachter et al, 1995), basal cell carcinoma (Yamamoto et al, 1997) and pulmonary adenocarcinoma (Imada et al, 2000). The accumulation of mast cells has been associated with enhanced growth and invasion of several human cancers (Ribatti et al, 2001).…”