Biochemical Markers for Assessment of Bone Metastases in Patients with Breast Cancer

乳癌患者尿中Deoxypyridinoline及血清中骨特殊鹼性磷酸酵素

侯明鋒(Ming-Feng Hou) ； 蔡麗玉(Li-Yu Tsai) ； 蔡世盟(Shih-Meng Tsai) ； 黃哲人(Che-Jen Huang) ； 黃裕勝(Yu-Sheng Huang) ； 謝建勳(Jan-Sing Hsieh) ； 陳漢文(Hon-Man Chan) ； 王照元(Jaw-Yuan Wang) ； 莊捷翰(Chieh-Han Chuang) ； 陳芳銘(Fan-Ming Chen) ； 黃宗人(Tsun)

《The Kaohsiung Journal of Medical Sciences》 15卷8期 (1999/08) Pp. 452-460

https://doi.org/10.6452/KJMS.199908.0452

摘要

乳癌患者常見骨髓轉移造成溶骨性及成骨性沈積物，而利用不同標記來定量骨質轉換形態，可以評估乳癌骨骼轉移的變化，而尿液中Deoxypyridinoline(Dpd)是骨質內膠原分子在骨骼破壞分解時至尿中的產物，骨特殊鹼性磷酸酵素是一種同形酵素，位於成骨細胞的外膜且在骨骼形成時釋放至血液中，利用此兩種生化標記，可以來預測乳癌轉移至骨骼的轉換情形。利用酵素免疫測定42例健康女性及148例乳癌患者的尿中Dpd及骨特殊鹼性酸酵素值，且同時比較其他生化標記，如癌胚胎抗原，CA15-3，組織多胜抗原，組織多胜特殊抗原，總鹼性磷酸酵素，結果顯示尿中Dpd/Creatinine在乳癌患者較控制組為高（平均值8.19±3.95比5.69±1.26nmol/mmol, P＜0.05），但在骨特殊鹼性磷酸酵素兩組則無統計性有意義差異，而乳癌骨骼轉移者其總鹼性磷酸酵素及骨特殊鹼性磷酸酵素，Dpd/Cre與骨特殊鹼性磷酸酵素比值較骨骼未轉移者高（P＜0.05）。在晚期乳癌（即第三期及第四期）其尿中Dpd/Cre比值較早期乳癌（即第一期及第二期）高（P＜0.05）。但骨特殊鹼性磷酸酵素則只在第四期上升（P＜0.05）。另外在尿中Dpd/Cre隨著骨骼轉移程度逐漸上升時，骨特殊鹼性磷酸酵素只有在最嚴重骨骼轉移時上升（P＜0.05）。而（Dpd/Cre）與骨特殊鹼性磷酸酵在第三期及第四期上升，但反而在中度骨骼轉移最低，顯示乳癌骨骼轉患者其骨骼溶骨活動力在早期時增加，之後才呈現成骨活動力上升，並代表骨骼再塑情形，在比較其他傳統生化標記亦發現其最佳診斷效能順序則是CEA, Dpd/Cre, （Dpd/Cre）/B-Alp, CA15-3，組織多胜抗原，組織多胜特殊抗原，骨特殊鹼性磷酸酵素，總鹼性磷酸酵素，因此連中Dpd/Cre比在評估乳癌骨骼轉移是個有用的生化標記，雖然骨特殊鹼性磷酸酵素並不比傳統生化標記為佳，但在Dpd/Cre與骨特殊鹼性磷酸酵素比在評估骨骼轉移後的再造是有其必要性。

並列摘要

Breast cancer commonly metastasizes to bones, producing both osteolytic and osteoblastic deposits. Different markers for quantitative determination of bone turnover have been developed to evaluate bone metastases of breast cancer. The urinary deoxypyridionline (Dpd), a crosslink product of collagen molecules found in bone and excreted in urine during bone degradation, and bone specific alkaline phosphatase (B-ALP), an isoenzyme localized in the membrane of osteoblasts and released in circulation during bone formation, were recently described as a group of markers of bone turnover in metastatic cancer. The urinary Dpd/creatinine (Cre) ratios and the serum B-ALP activity were determined in the samples from 148 patients who suffered from breast cancer (BC patients) with or without bone metastases, and 42 healthy women. For comparison, other biochemical markers, e.g. carcinoembryonic antigen (CEA), CA15-3, tissue polypeptide antigen (TPA), tissue polypeptide specific antigen (TPSA), and total alkaline phosphatase (T-ALP) in these samples were also evaluated. The results showed that there was a significant difference in urinary Dpd/Cre ratio between the control group and the patients with breast cancer (BC group) (mean±S.D., 5.69±1.26 vs. 8.19±3.95 nM/mM, P＜0.05). However, there was no significant difference between their B-ALP activities in the two groups. In addition, the BC patients with bone metastases showed elevated urinary Dpd/Cre ratios and B-ALP activities and ratios of (Dpd/Cre)/B-ALP in compare with BC patients without bone metastases (P＜0.05). Meanwhile, the urinary Dpd/Cre ratios (10.50±5.04 nmol/mmol) in the advanced stage of BC patients were higher than those in an early stage (7.45±3.23 nmol/mmol) (P＜0.05), but their serum B-ALP activities increased only in stage IV (P＜0.05). The urinary Dpd/Cre ratios also increased progressively according to the degree of bone metastases (P＜0.05), but their serum B-ALP activities only increased in severe bone metastases (P＜0.05). The results showed that the increase of a bone osteolytic activity took place earlier than that of a bone osteoblastic activity in the metastatic BC patients. In compare with other conventional markers, the best diagnostic efficiency of biochemical markers, analyzed by step wise discriminate analysis, was provided by CEA followed by Dpd/Cre ratio, CA15-3, TPA, TPSA, B-ALP and T-ALP. We conclude that showed the urinary Dpd/Cre ratio was a useful tumor marker to evaluate breast cancer with bone metastases.

並列關鍵字

breast cancer ； deoxypyridinoline ； bone specific alkaline phosphatase