Sakamoto A, Katakami H, Mukae H, Taniguchi H, Maki H, Ashitani J, Ihi T, Dohtsu Y, Matsukura S
Third Department of Internal Medicine, Miyazaki Medical College, Japan.
Nihon Kyobu Shikkan Gakkai Zasshi. 1995 Jan;33(1):34-8.
Hypercalcemia and leukocytosis are often associated with primary lung cancer as a paraneoplastic syndrome. Recently, parathyroid hormone-related protein (PTHrP) and granulocyte colony stimulating factor (G-CSF) have been identified as major causative peptides for hypercalcemia and leukocytosis, respectively. We studied four men with advanced primary lung cancer (stages from IIIA to IV) who presented with hypercalcemia (corrected serum calcium levels: 10.5 mg/dl) and leukocytosis (WBC > 10,000 per mm3). The age of the patients ranged from 59 to 79 years old. The pathological subtypes were squamous cell carcinoma in three and adenocarcinoma in one. The mean serum calcium levels and leukocyte counts were 15.8 +/- 1.4 mg/dl (mean +/- SE) and 24,800 +/- 3,253 cells/mm3 (mean +/- SE), respectively. Abnormally high serum levels of PTHrP and G-CSF were found in three patients (mean +/- SE: 137 +/- 68 pg/ml; normal range in human serum, < 16 pg/ml), and in all four (mean +/- SE: 72 +/- 7.7 pg/ml; normal range in human serum, < 20 pg/ml), respectively. Immuno-histochemical examination of cancerous tissue obtained from these patients showed positive staining for both PTHrP and G-CSF within the cytoplasm of all the cancerous tissue. These results suggest that the association of hypercalcemia and leukocytosis in patients with advanced primary lung cancer is caused by production of both PTHrP and G-CSF by cancerous tissue.
高钙血症和白细胞增多症常与原发性肺癌相关，作为一种副肿瘤综合征。最近，甲状旁腺激素相关蛋白（PTHrP）和粒细胞集落刺激因子（G-CSF）已分别被确定为高钙血症和白细胞增多症的主要致病肽。我们研究了4例晚期原发性肺癌（IIIA期至IV期）患者，他们均出现高钙血症（校正血清钙水平：10.5mg/dl）和白细胞增多症（白细胞计数>10,000/mm³）。患者年龄在59至79岁之间。病理亚型为3例鳞状细胞癌和1例腺癌。平均血清钙水平和白细胞计数分别为15.8±1.4mg/dl（均值±标准误）和24,800±3,253个细胞/mm³（均值±标准误）。在3例患者中发现血清PTHrP水平异常升高（均值±标准误：137±68pg/ml；人血清正常范围，<16pg/ml），在所有4例患者中均发现血清G-CSF水平异常升高（均值±标准误：72±7.7pg/ml；人血清正常范围，<20pg/ml）。对这些患者的癌组织进行免疫组织化学检查显示，所有癌组织的细胞质内PTHrP和G-CSF均呈阳性染色。这些结果表明，晚期原发性肺癌患者中高钙血症和白细胞增多症的关联是由癌组织产生PTHrP和G-CSF所致。
