Liao John B, Yip Yuen Yee, Swisher Elizabeth M, Agnew Kathy, Hellstrom Karl Erik, Hellstrom Ingegerd
Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA 98195, USA.
Department of Pathology, University of Washington School of Medicine, Seattle, WA 98195, USA.
Gynecol Oncol. 2015 Jun;137(3):430-5. doi: 10.1016/j.ygyno.2015.03.044. Epub 2015 Apr 9.
To measure HE4 levels in urine from normal donors, patients with LMP tumors and ovarian cancer patients and to correlate levels with clinical factors in ovarian cancer patients.
Archived samples from controls, patients with LMP tumors and ovarian cancer were tested using commercial assays, including serially collected serum and urine samples from women treated for stage III/IV serous ovarian cancer.
Five of 6 patients with stage I/II and 26 of 36 stage III/IV serous ovarian cancer patients had HE4-positive urines, similar to serum samples (4 of 5 stage I/II and 26 of 34 stage III/IV) when tested at the same level of specificity (95%). Urine HE4 was more sensitive in LMP tumors: 9 of 32 urines (28%) HE4-positive versus 3 of 68 sera (4.4%, p=0.002). Mean levels of serum CA125 and HE4 decreased comparably in patients during initial treatment regardless of their primary platinum response, but mean urine HE4 levels decreased only 7% in primary platinum resistant patients while decreasing 68% in those who were sensitive. By 7months after diagnosis, urine HE4 levels were higher in primary platinum resistant patients compared to those who proved to be sensitive (p=0.051) and persisted 12months after diagnosis (p=0.014). HE4 values in urine also became positive in advance of clinical recurrence in several women while serum HE4 and serum CA-125 remained normal.
Measuring HE4 in urine complements serum assays for the detection of ovarian cancer and may allow identification of patients at high risk for primary platinum resistance.
检测正常供体、低恶性潜能（LMP）肿瘤患者及卵巢癌患者尿液中的HE4水平，并将其水平与卵巢癌患者的临床因素相关联。
使用商业检测方法对来自对照组、LMP肿瘤患者及卵巢癌患者的存档样本进行检测，其中包括对III/IV期浆液性卵巢癌患者治疗期间连续采集的血清和尿液样本。
6例I/II期浆液性卵巢癌患者中有5例尿液HE4呈阳性，36例III/IV期浆液性卵巢癌患者中有26例尿液HE4呈阳性，与血清样本情况相似（5例I/II期患者中有4例，34例III/IV期患者中有26例），检测特异性相同（95%）。尿液HE4在LMP肿瘤中更具敏感性：32份尿液中有9份（28%）HE4呈阳性，而68份血清中有3份（4.4%）呈阳性（p=0.002）。在初始治疗期间，无论患者对铂类药物的原发性反应如何，血清CA125和HE4的平均水平均有相当程度下降，但原发性铂类耐药患者尿液HE4平均水平仅下降7%，而敏感患者则下降68%。诊断后7个月，原发性铂类耐药患者的尿液HE4水平高于敏感患者（p=0.051），且在诊断后12个月仍持续较高（p=0.014）。在数名女性中，尿液HE4值在临床复发前转为阳性，而血清HE4和血清CA-125仍保持正常。
检测尿液中的HE4可补充血清检测用于卵巢癌的检测，且可能有助于识别原发性铂类耐药的高危患者。
