Elsevier

Lung Cancer

Volume 29, Issue 3, 1 September 2000, Pages 169-177
Lung Cancer

Prognostic significance of platelet and microvessel counts in operable non-small cell lung cancer

https://doi.org/10.1016/S0169-5002(00)00124-0Get rights and content

Abstract

Background: Microvessel density, an indirect measure of angiogenesis, has been shown to be an independent prognostic marker in many solid tumours including non-small cell lung cancer (NSCLC). Platelets transport and release angiogenic growth factors. Platelets are increasingly likely to adhere to tumour microvessels due to raised expression of platelet-binding proteins and stasis in blood-flow. Increased vascular permeability in tumour microvessels facilitates platelet extravasation into the extracellular matrix. Adherence and extravasation both lead to platelet activation and release of growth factors capable of instigating the angiogenic process. Methods: A total of 181 patients were identified who underwent resection of stage I–IIIa NSCLC with a post-operative survival >60 days. Patients were followed-up for a minimum of 24 months. Sections from the tumour periphery were stained for the endothelial marker CD34 (Novocastra NCL-END) using standard ABC immunohistochemistry. Chalkley counting was used to assess microvessel density. Results: A pre-operative platelet count greater than the median and above the normal range (>400) was associated with a poor outcome (P=0.01 and P=0.04, respectively). Tumours with an above median and high Chalkley count (upper tertile) had a worse prognosis (P=0.007 and P=0.0006, respectively). There was no association between platelet count and Chalkley count. Conclusions: Platelet and microvessel counts are both potential prognostic markers for NSCLC. The role of platelets in the angiogenic process needs to be further investigated.

Introduction

Angiogenesis is the formation of new blood vessels from the endothelium of the existing vasculature and is a requirement for solid tumour growth beyond 1–2 mm in diameter [1]. Currently the best predictor of outcome in non-small cell lung cancer (NSCLC) is the T, N, M stage [2]. Recent research suggests that microvessel density may be an important independent prognostic indicator in this disease [3], [4], [5], [6] although some studies have not found microvessel counts to be predictive for survival [7], [8].

Thrombocytosis is associated with a worse prognosis in solid tumours including primary lung cancer [9], [10]. Angiogenic factors including vascular endothelial growth factor (VEGF) are transported by platelets [11] and released when platelets are activated [12]. Platelet count has been shown to be associated with serum VEGF concentration in solid tumours [11], [13], [14]. VEGF is the most potent and specific growth factor for endothelial cells and plays an important role in angiogenesis [15]. VEGF also increases vascular permeability allowing leakage of plasma proteins, fibrin and platelets into the extracellular matrix [15]. Recently it has been proposed that platelets contribute to tumour-induced angiogenesis by locally releasing angiogenic growth factors such as VEGF [13], [16].

This study was aimed at evaluating the relationship between microvessel and pre-operative platelet counts in NSCLC and to see if these factors had an impact on survival.

Section snippets

Study population

This is a retrospective study of 181 patients with stage I–IIIa NSCLC who underwent surgical resection in Glenfield Hospital, Leicester, UK between 1991 and 1996 with a post-operative survival >60 days. No patient received neoadjuvant or adjuvant chemotherapy. Radiotherapy was given to 14 patients post-operatively for a positive resection margin. The follow-up ranged from 24 to 108 months (median 39.8 months). A total of 98 (54.1%) subjects died from a recurrence of their lung primary. Some 128

Clinicopathological findings

The clinicopathological findings are listed in Table 1. The stage of the tumour was prognostic (P=0.0001). Tumour spread to nodes was associated with poor prognosis (P=0.0007) and increasing nodal status was more significant (P<0.0001). The trend to worse survival with increasing T status did not reach significance (P=0.15). No other clinicopathological finding, including age, sex, grade or histological sub-type was associated with outcome.

Platelet count

The pre-operative platelet count was identified in 175

Discussion

The growth of a tumour beyond 1–2 mm in diameter requires the development of new blood vessels [1]. These vessels play an important role in tumorigenesis supplying nutrients and oxygen, disposing of metabolic waste products and allowing metastatic spread. The study showed that tumours with a high vessel count were associated with a worse survival. This is in agreement with several other studies showing an inverse relationship between vascularity and patient survival in NSCLC [3], [4], [5], [6].

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    Tumour and Angiogenesis Research Group.

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