Kasuga I, Makino S, Kiyokawa H, Katoh H, Ebihara Y, Ohyashiki K
First Department of Internal Medicine, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
Cancer. 2001 Nov 1;92(9):2399-405. doi: 10.1002/1097-0142(20011101)92:9<2399::aid-cncr1588>3.0.co;2-w.
Tumor-related leukocytosis is a paraneoplastic syndrome that is encountered occasionally in the clinical course of patients with lung carcinoma. Recently, autonomous production of hematopoietic cytokines (granulocyte-colony stimulating factor [G-CSF], granulocyte-macrophage-colony stimulating factor [GM-CSF], and interleukin-6 [IL-6]) were identified in some of these patients. However, the incidence and clinical characterization of this phenomenon have not been clarified.
During a 7-year period, 227 patients with carcinoma of the lung were investigated, and 33 patients were diagnosed with tumor-related leukocytosis. Except for one patient with small cell lung carcinoma, the other 32 patients had nonsmall cell lung carcinoma, and the highest incidence is recognized in large cell carcinoma. These 33 patients were examined for serum G-CSF, GM-CSF, and IL-6 levels using enzyme immunoassays and enzyme-linked immunosorbent assays. Tumor specimens were stained for antihuman cytokine (G-CSF, GM-CSF, and IL-6) monoclonal antibodies.
Sixteen patients showed high serum G-CSF levels, 4 patients showed high serum GM-CSF levels, and 18 patients showed high serum IL-6 levels. Twelve specimens stained positively against anti-G-CSF antibody. Two specimens stained positively against anti-GM-CSF antibody, and three specimens were stained positively against anti-IL-6 antibody, including one double positive specimen for both G-CSF and IL-6. All specimens that were positive for monoclonal antibodies were from patients with nonsmall cell lung carcinoma. These patients had a poor outcome compared with the other patients.
Tumor-related leukocytosis and cytokine production frequently occur in the clinical course of lung carcinoma, and this phenomenon is related mainly to nonsmall cell lung carcinoma. Its occurrence appears to be an ominous prognostic sign in patients with lung carcinoma.
肿瘤相关性白细胞增多症是一种副肿瘤综合征，在肺癌患者的临床病程中偶尔会遇到。最近，在其中一些患者中发现了造血细胞因子（粒细胞集落刺激因子[G-CSF]、粒细胞-巨噬细胞集落刺激因子[GM-CSF]和白细胞介素-6[IL-6]）的自主产生。然而，这种现象的发生率和临床特征尚未阐明。
在7年期间，对227例肺癌患者进行了调查，33例被诊断为肿瘤相关性白细胞增多症。除1例小细胞肺癌患者外，其他32例患者为非小细胞肺癌，其中大细胞癌的发生率最高。使用酶免疫测定法和酶联免疫吸附测定法对这33例患者的血清G-CSF、GM-CSF和IL-6水平进行检测。肿瘤标本用抗人细胞因子（G-CSF、GM-CSF和IL-6）单克隆抗体染色。
16例患者血清G-CSF水平升高，4例患者血清GM-CSF水平升高，18例患者血清IL-6水平升高。12份标本抗G-CSF抗体染色呈阳性。2份标本抗GM-CSF抗体染色呈阳性，3份标本抗IL-6抗体染色呈阳性，其中1份标本G-CSF和IL-6均为双阳性。所有单克隆抗体阳性的标本均来自非小细胞肺癌患者。与其他患者相比，这些患者的预后较差。
肿瘤相关性白细胞增多症和细胞因子产生在肺癌临床病程中经常发生，这种现象主要与非小细胞肺癌有关。其发生似乎是肺癌患者预后不良的征兆。
