Baseline Serum HE4 But Not Tissue HE4 Expression Predicts Response to the Levonorgestrel-Releasing Intrauterine System in Atypical Hyperplasia and Early Stage Endometrial Cancer

• Main Authors: Roya Behrouzi, Neil A. J. Ryan, Chloe E. Barr, Abigail E. Derbyshire, Y. Louise Wan, Zoe Maskell, Katie Stocking, Philip W. Pemberton, James Bolton, Rhona J. McVey, Emma J. Crosbie
• Format: Article
• Language: English
• Published: MDPI AG 2020-01-01
• Series: Cancers
• Subjects: he4; endometrial cancer; atypical hyperplasia; biomarker; therapy; response; levonorgestrel-releasing intrauterine system; lng-ius
• Online Access: https://www.mdpi.com/2072-6694/12/2/276

The levonorgestrel-releasing intrauterine system (LNG-IUS) is a conservative management option for atypical hyperplasia (AH) and low grade early stage endometrial cancer (EEC), but around 1 in 3 patients fail to respond to treatment. The aim of this study was to investigate if serum and/or tissue HE4 expression could predict response to LNG-IUS therapy. Patients with AH or presumed Stage I EEC had serum and endometrial samples taken at baseline and at 3-month intervals over 12 months post-insertion of LNG-IUS. 74 patients were recruited and baseline demographics recorded. Of 57 patients for whom response was histologically determinable, 39 (68%) were responders and 18 (32%) non-responders. Mean baseline serum HE4 was significantly lower in responders (62.1 &#177; 1.1 pM, 95% confidence interval (CI) 52.7&#8722;73.2), compared to non-responders (125.6 &#177; 1.3 pM, 95% CI 74.5&#8722;211.7, <i>p</i> = 0.014), including when considering age, BMI, menopausal status, smoking status, and histological grade as covariables (<i>p</i> = 0.005). Baseline tissue HE4 expression was not significantly different in responders compared to non-responders (<i>p</i> = 0.999). Responders showed a significant mean reduction (&#8722;9.8 &#177; 3.4%, 95% CI &#8722;16.7 to &#8722;2.8%, <i>p</i> = 0.008) in serum HE4 between baseline and 3 months (<i>p</i> = 0.008), whereas non-responders showed no significant change (<i>p</i> = 0.676). Neither responders nor non-responders showed a significant percentage change in serum HE4 from baseline beyond 3 months (<i>p</i> &gt; 0.05). Change in serum HE4 between baseline and 3 and 6 months and tissue HE4 tissue expression between baseline and 3, 6, and 12 months was not significantly different in responders compared to non-responders (<i>p</i> &gt; 0.05). This study suggests that baseline serum HE4, but not baseline tissue HE4 expression, is independently predictive of response to the LNG-IUS and could be used to guide management decisions.