Elsevier

Lung Cancer

Volume 31, Issues 2–3, March 2001, Pages 213-219
Lung Cancer

Increased serum levels of basic fibroblast growth factor in lung cancer patients: relevance to response of therapy and prognosis

https://doi.org/10.1016/S0169-5002(00)00187-2Get rights and content

Abstract

Angiogenesis is controlled by inhibitors and angiogenic factors. Among these, basic fibroblast growth factor (bFGF) is closely involved in cancer proliferation and has been related to progression and prognosis of various cancers, including lung cancer. To evaluate the role of bFGF, we measured serum levels of bFGF from healthy controls (Ctrl) and 106 patients with lung cancer, including 31 adenocarcinomas (AD), 29 squamous cell carcinomas (SQ), and 46 small cell carcinomas (SCLC), by enzyme-linked immunosorbent assays. Moreover, we evaluated the relationship between serum levels of bFGF and clinical outcome. Serum levels of bFGF in AD, SQ, SCLC, and Ctrl were 7.6 (0.5–32.5) (median (range)), 7.4 (0.5–36.7), 7.1 (0.5–34.8) and 3.0 (1.5–6.0) pg/ml, respectively (P<0.05). Serum bFGF levels did not differ between clinical stages in non-small cell lung cancer (NSCLC; AD+SQ). In SCLC, we found a significant difference in serum levels of bFGF between chemotherapy (and/or radiotherapy) responders (complete response+partial response) and non-responders (no change+progressive disease) (9.2 (0.6–34.8), 4.4 (0.5–17.4) pg/ml, respectively (P=0.018)), whereas there was no difference in NSCLC. Moreover, serum bFGF levels in SCLC patients had significant impact in prognosis by uni and multivariate analysis (P=0.014, 0.018, respectively). We concluded that bFGF has an important role in the prognosis of patients with SCLC.

Introduction

Angiogenesis is sprout formation of capillaries from pre-existing vessels, and its process is intricate [1]. In adults, it is important in pathological status, such as wound healing and tumor growth [2]. The roles of angiogenesis in solid tumor growth are well recognized. Tumor augmentation requires persistent new vessel growth, which is tightly controlled by endogenous angiogenic factors and inhibitors [3]. Angiogenesis is also important for metastatic spread of tumor cells [4]. Weidner et al. [5] showed that microvessel counts and density grades correlated with degree of metastasis in invasive breast carcinoma, and the same findings were observed in malignant melanoma [6] and cervical carcinoma [7]. In lung cancer, both the biological and clinical significance of tumor angiogenesis have been studied. There were several reports that indicated intratumoral vessel density correlated to poor prognosis in non-small cell lung cancer (NSCLC) [8], [9], [10]. However, Pastorino et al. [11], reported opposing data, and prognostic values of intratumoral microvessel counts remain controversial in lung cancer.

Basic fibroblast growth factor (bFGF) is a mitogenic and chemotactic growth factor for a variety of cells and is one of several potent angiogenic factors. Basic FGF is considered to be involved in prognosis of cancer patients, however there has been no report about comparison of serum bFGF with vascularities in the same cancer patient. Basic FGF is encoded by a single copy gene, which encodes several isoforms ranging from 18 to 24 kDa, including heparin-binding domain [12]. Overexpression of bFGF in pancreatic cancer is closely involved in cancer proliferation and is associated with tumor stage and prognosis [13]. Recently elevated levels of serum bFGF have been reported in patients with renal, breast, and cervical carcinoma [14], [15], [16]. In the present paper, we hypothesized that increased levels of serum bFGF in patients with lung cancer is relevant to clinical outcomes such as response to chemotherapy and prognosis.

Section snippets

Patients

We examined 17 healthy controls (Ctrl) and 106 lung cancer patients admitted to National Kinki Central Hospital for Chest Diseases (31 patients with adenocarcinoma of the lung (AD), 29 patients with squamous cell carcinoma of the lung (SQ), and 46 patients with small cell lung cancer (SCLC)). All patients were histologically or cytologically diagnosed by transbronchial biopsies (or sputum examinations). We carefully excluded the patients with interstitial pneumonia, pulmonary fibrosis, and

bFGF in lung cancer patients and healthy controls

Median (range) of serum bFGF levels in patients with AD, SQ, SCLC, and in healthy controls (Ctrl) were 7.6 (0.5–32.5), 7.4 (0.5–36.7), 7.1 (0.5–34.8), and 3.0 (1.5–6.0) pg/ml, respectively (Fig. 1). Serum levels of bFGF in patients with all histological types of lung cancer were significantly higher than in Ctrl (P<0.05, each). However, there was no significant difference among each histological type. Serum levels of bFGF in Ctrl were compatible with other studies [17], [19]. A high bFGF level

Discussion

Serum bFGF levels in patients with various malignant tumors were reported to increase [14], [15], [16]. Brattström et al. [19] reported that elevated levels of serum bFGF were detected in 26/68 (38%) patients with NSCLC. Nguyen et al. [20] demonstrated high levels of bFGF in urine from 950 patients with a wide spectrum of cancers, including lung cancer, although Linder et al. [21] reported that serum bFGF levels in 31 patients with lung cancer were not statistically significantly higher than

Acknowledgements

We thank Yuki Hirochi for technical support. This work was supported in part by Grant in aid for Cancer Research (10–27) from the Ministry of Health and Welfare, Japan.

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