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Platelet-Derived Endothelial Cell Growth Factor/Thymidine Phosphorylase Concentrations Differ in Small Cell and Non-small Cell Lung Cancer^*

^* From the Department of Surgery II (Drs. Yamashita, Ogawa, and Abe), Kumamoto University School of Medicine, Kumamoto, Japan; and the Nippon Roche Research Center (Dr. Nishida), Kajiwara, Kamakura, Kanagawa, Japan.

Correspondence to: Michio Ogawa, MD, Department of Surgery II, Kumamoto University School of Medicine, Honjo 1–1-1, Kumamoto 860-8556, Japan; e-mail: michioab{at}kaiju.medic.kumamoto-u.ac.jp

Objective: Platelet-derived endothelial cell growth factor (PD-ECGF)/thymidine phosphorylase (TP) has been implicated in cancer angiogenesis, which is critical for tumor growth and metastasis. We investigated the relationship between the tissue concentration of PD-ECGF/TP and the clinicopathologic status in human lung cancer.

Methods: The concentrations of PD-ECGF/TP in the tumor extracts of 139 primary human lung carcinomas were measured by using a highly specific and sensitive enzyme-linked immunosorbent assay.

Results: PD-ECGF/TP was detected in the extracts from 137 of 139 specimens at concentrations that ranged from 2.0 to 169.5 U/mg protein. PD-ECGF/TP concentrations in patients with adenocarcinoma (n = 73) and squamous cell carcinoma (n = 49) were (mean ± SD) 30.7 ± 22.9 U/mg protein (range, 7.6 to 169.5 U/mg protein) and 32.0 ± 19.8 U/mg protein (range, 8.0 to 84.4 U/mg protein), respectively. No significant difference was found in the PD-ECGF/TP concentration between these two types of non-small cell lung cancer (NSCLC). However, a > 8-fold lower mean concentration of PD-ECGF/TP was found in tissue extracts from small cell lung cancer (SCLC) (n = 17; 3.65 ± 2.01 U/mg protein, ranging from undetectable to 6.1 U/mg protein) than in those from adenocarcinomas (p = 0.00005) or squamous cell carcinomas (p < 0.00001).

Conclusions: The striking difference in PD-ECGF/TP concentrations between SCLC and NSCLC suggests that these two types of lung cancer use alternative pathways for angiogenesis. The present study suggests that inhibitors of PD-ECGF/TP, which have been recently developed and are under laboratory investigation to test their effectiveness as treatments for various types of cancer, may not be effective against SCLC.

Key Words: enzyme-linked immunosorbent assay • non-small cell lung cancer • platelet-derived endothelial cell growth factor • small cell lung cancer • thymidine phosphorylase

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