O'Neill K L, Hoper M, Odling-Smee G W
Department of Microbiology, Brigham Young University, Provo, Utah 84602.
J Natl Cancer Inst. 1992 Dec 2;84(23):1825-8. doi: 10.1093/jnci/84.23.1825.
Our previous study of thymidine kinase (TK) levels in the serum of breast cancer patients demonstrated a statistically significant positive correlation with cancer stage. In postsurgical follow-up studies of 20 patients with primary breast cancer, total serum TK levels rose with disease recurrence and continued to rise with disease progression but decreased with treatment response.
This study was designed to examine whether TK levels in primary breast tumors can be used to predict recurrence and to establish the relationship between TK levels and estrogen receptor (ER) status and recurrence.
Eighty-six patients with breast cancer were entered in this study. Tumors were assessed for ER status and TK levels, and the patients had follow-up for recurrence over a period of 41 months. By calculating the percent of TK activity in the presence of adenosine triphosphate (ATP) or cytidine triphosphate (CTP), we estimated the relative contributions of TK isozymes TK1 and TK2 to total TK activity.
Total TK (TK1 plus TK2) levels in tumors were significantly (P < .001) elevated in patients who subsequently had recurrence compared with levels in those who did not. Calculations of the percent of TK activity in the presence of ATP or CTP showed that this elevation was due to increased TK1 isozyme levels. ER-negative (ER-) patients had significantly (P < .001) increased TK1 levels relative to those in ER-positive (ER+) patients. ER- patients with recurrence had significantly (P < .001) elevated total tumor TK levels compared with levels in those who did not have recurrence, and calculation of percent of TK activity with ATP or CTP indicated elevated TK1 levels. A similar pattern of increased levels of total tumor TK and TK1 was observed in ER+ patients with recurrence.
The results indicate that total tumor TK levels were significantly higher in breast cancer patients who subsequently had recurrence than levels in those who did not. This finding appears to be largely caused by higher levels of TK1.
Higher TK1 levels in tumors in patients who subsequently had disease recurrence almost certainly indicate a high rate of proliferation in such tumors at the time of excision. It appears that TK is a potentially useful marker in the management of breast cancer. With measurement of levels of TK, particularly TK1, in breast tumors and serum, it may be possible to predict recurrence of breast cancer.
我们之前对乳腺癌患者血清中胸苷激酶（TK）水平的研究表明，其与癌症分期存在统计学上显著的正相关。在对20例原发性乳腺癌患者的术后随访研究中，血清总TK水平随疾病复发而升高，并随疾病进展持续升高，但随治疗反应而降低。
本研究旨在探讨原发性乳腺肿瘤中的TK水平是否可用于预测复发，并确定TK水平与雌激素受体（ER）状态及复发之间的关系。
86例乳腺癌患者纳入本研究。评估肿瘤的ER状态和TK水平，并对患者进行为期41个月的复发随访。通过计算在三磷酸腺苷（ATP）或三磷酸胞苷（CTP）存在下TK活性的百分比，我们估计了TK同工酶TK1和TK2对总TK活性的相对贡献。
与未复发患者相比，随后复发的患者肿瘤中的总TK（TK1加TK2）水平显著升高（P <.001）。在ATP或CTP存在下计算TK活性百分比表明，这种升高是由于TK1同工酶水平增加所致。与雌激素受体阳性（ER+）患者相比，雌激素受体阴性（ER-）患者的TK1水平显著升高（P <.001）。复发的ER-患者肿瘤总TK水平显著高于未复发患者（P <.001），用ATP或CTP计算TK活性百分比表明TK1水平升高。在复发的ER+患者中也观察到肿瘤总TK和TK1水平升高的类似模式。
结果表明，随后复发的乳腺癌患者肿瘤总TK水平显著高于未复发患者。这一发现似乎主要是由较高的TK1水平引起的。
随后疾病复发患者肿瘤中较高的TK1水平几乎肯定表明此类肿瘤在切除时增殖率较高。看来TK是乳腺癌管理中一个潜在有用的标志物。通过测量乳腺肿瘤和血清中的TK水平，特别是TK1水平，可能预测乳腺癌的复发。
