Non-invasive detection of endometrial cancer by DNA methylation analysis in urine
CLINICAL EPIGENETICS
Authors: van den Helder, Rianne; Wever, Birgit M. M.; van Trommel, Nienke E.; van Splunter, Annina P.; Mom, Constantijne H.; Kasius, Jenneke C.; Bleeker, Maaike C. G.; Steenbergen, Renske D. M.
Abstract
Background The incidence of endometrial cancer is rising, and current diagnostics often require invasive biopsy procedures. Urine may offer an alternative sample type, which is easily accessible and allows repetitive self-sampling at home. Here, we set out to investigate the feasibility of endometrial cancer detection in urine using DNA methylation analysis. Results Urine samples of endometrial cancer patients (n = 42) and healthy controls (n = 46) were separated into three fractions (full void urine, urine sediment, and urine supernatant) and tested for three DNA methylation markers (GHSR, SST, ZIC1). Strong to very strong correlations (r = 0.77-0.92) were found amongst the different urine fractions. All DNA methylation markers showed increased methylation levels in patients as compared to controls, in all urine fractions. The highest diagnostic potential for endometrial cancer detection in urine was found in full void urine, with area under the receiver operating characteristic curve values ranging from 0.86 to 0.95. Conclusions This feasibility study demonstrates, for the first time, that DNA methylation analysis in urine could provide a non-invasive alternative for the detection of endometrial cancer. Further investigation is warranted to validate its clinical usefulness. Potential applications of this diagnostic approach include the screening of asymptomatic women, triaging women with postmenopausal bleeding symptoms, and monitoring women with increased endometrial cancer risk.
Immunohistochemical evidence for Zic1 coexpression with -catenin in the myofibroblast of Dupuytren disease
SCANDINAVIAN JOURNAL OF PLASTIC AND RECONSTRUCTIVE SURGERY AND HAND SURGERY
Authors: Degreef, Ilse; De Smet, Luc; Sciot, Raf; Cassiman, Jean-Jacques; Tejpar, Sabine
Abstract
The active cellular component in Dupuytren disease (DD) is the -smooth muscle actin (-SMA) containing myofibroblast. The underlying regulatory processes in activation of myofibroblasts resemble the pathophysiology of certain types of cancer. Accumulation of -catenin has been shown in many fibroproliferative processes, including DD and, recent findings attributed a possible role to the Zic1 transcription factor. To assess Zic1 expression in DD and investigate its relation with the accumulation of -catenin, neighbouring tissue samples in 20 patients with DD were stained immunohistochemically with monoclonal antibodies for -catenin, -SMA, and Zic1. Histological appearance was staged according to Luck. Cell-rich areas with accumulation of -catenin in myofibroblasts that stained for -SMA and showed apparent Zic1 coexpression were obvious. This coexpression seemed independent of proliferative or involutional histological staging. We found only Zic1 expression in residual stages. A different pattern of expression of protein in the residual stage may support earlier suggestions of a cellular heterogeneity with the existence of different cell (sub-)populations in nodules and cords. On the other hand coexpression of Zic1 and -catenin may indicate a relation between Zic1 and the Wnt-pathway. Further studies are needed to elucidate cellular origin, potential heterogeneity and activity of the myofibroblasts in DD, and to define the exact role of Zic1 in fibroproliferative processes, wound healing, and cancer. The fibroblast in DD is an interesting model for future experiments.