Dellacono F R, Spiro J, Eisma R, Kreutzer D
Department of Surgery, University of Connecticut Health Center, School of Medicine, Farmington 06030-3105, USA.
Am J Surg. 1997 Nov;174(5):540-4. doi: 10.1016/s0002-9610(97)00169-4.
Basic fibroblast growth factor (bFGF) is a potent angiogenic factor implicated in tumor growth and metastasis. To determine if bFGF and basic fibroblast growth factor receptor 1 (bFGFR1) and 2 (bFGFR2) are upregulated in head and neck squamous cell carcinoma (HNSCC), we measured the distribution and levels of each in HNSCC specimens and control specimens.
Head and neck squamous cell carcinoma and control tissue specimens were analyzed qualitatively (40 patients, 10 controls) using immunohistochemistry, and quantitatively (26 patients, 8 controls) using immunoassays and graded immunohistochemistry. Control tissue consisted of palatal tissue obtained during uvulopalatopharyngoplasty (UPPP).
Immunohistochemical analysis revealed that bFGF, bFGFR1, and bFGFR2 antigens were strongly associated with cancer and vascular endothelial cells in HNSCC. Control tissue had moderate staining of vascular endothelium and no stromal staining. Quantitative analysis of bFGF in tissue homogenates indicated that bFGF levels in cancer specimens were significantly elevated compared with control tissues (420.3 +/- 360.9 ng/mg total protein versus 49.2 +/- 48.7, respectively, P < or =0.05). When analyzed by clinical stage, bFGF levels were significantly higher in stage III patients as compared with stage IV patients (P < or =0.01). When immunohistochemistry results were correlated with clinical stage, bFGF (P < or =0.01), bFGFR1 (P < or =0.001), and bFGFR2 (P < or =0.0001) staining was significantly more intense in the cancer cells of stage III versus stage IV patients.
Enhanced expression of bFGF and bFGF receptors by cancer and vascular endothelial cells is present in HNSCC, and may contribute to tumor growth and metastasis in HNSCC by mediating angiogenesis. Strategies aimed at decreasing the expression of bFGF and its receptors may be of therapeutic benefit in HNSCC, particularly at an early stage of disease.
碱性成纤维细胞生长因子(bFGF)是一种强效血管生成因子,与肿瘤生长和转移有关。为了确定bFGF以及碱性成纤维细胞生长因子受体1(bFGFR1)和2(bFGFR2)在头颈部鳞状细胞癌(HNSCC)中是否上调,我们检测了它们在HNSCC标本和对照标本中的分布及水平。
对头颈部鳞状细胞癌和对照组织标本进行定性分析(40例患者,10例对照)采用免疫组织化学法,定量分析(26例患者,8例对照)采用免疫测定法和免疫组织化学分级法。对照组织由悬雍垂腭咽成形术(UPPP)期间获取的腭部组织组成。
免疫组织化学分析显示,bFGF、bFGFR1和bFGFR2抗原在HNSCC中与癌细胞及血管内皮细胞密切相关。对照组织的血管内皮有中度染色,间质无染色。组织匀浆中bFGF的定量分析表明,癌组织标本中的bFGF水平与对照组织相比显著升高(分别为420.3±360.9 ng/mg总蛋白和49.2±48.7 ng/mg总蛋白,P≤0.05)。按临床分期分析时,III期患者的bFGF水平显著高于IV期患者(P≤0.01)。当免疫组织化学结果与临床分期相关联时,III期患者癌细胞中bFGF(P≤0.01)、bFGFR1(P≤0.001)和bFGFR2(P≤0.0001)的染色明显比IV期患者更强。
HNSCC中癌细胞和血管内皮细胞存在bFGF及其受体的表达增强,可能通过介导血管生成促进HNSCC的肿瘤生长和转移。旨在降低bFGF及其受体表达的策略可能对HNSCC具有治疗益处,尤其是在疾病早期。