Carcinoma in situ testis displays permissive chromatin modifications similar to immature foetal germ cells

BACKGROUND: The majority of testicular germ cell cancers develop through a pre-invasive carcinoma in situ (CIS) stage. The CIS cell is a neoplastic counterpart of foetal germ cells. During their development, foetal germ cells undergo extensive and essential epigenetic modifications, but little is known about epigenetic patterns in CIS cells. METHODS: Immunohistochemistry was used to investigate epigenetic patterns in CIS, germ cell tumours, normal adult and foetal testicular tissue. RESULTS: CIS cells show low levels of DNA methylation and repressive histone modifications H3K9me2 and H3K27me3, but high levels of H3K9 acetylation, H3K4 methylation and H2A.Z, which all are associated with an activated and accessible chromatin structure. Collectively this renders a permissive chromatin structure and in accordance high levels of RNA polymerase II activity and proliferation (Ki-67 and mitotic index) is observed in CIS cells. Epigenetic patterns similar to that of CIS cells were observed in human gonocytes present within sex cords in foetal testes but correspond to migrating primordial germ cell in mice. Development of overt tumours involves epigenetic repression of the chromatin. CONCLUSION: CIS cells have a permissive and foetal-like chromatin structure, which is associated with a high transcriptional and proliferative activity, likely empowering neoplastic transformation. Developmental epigenetic cues in foetal germ cells are substantially different between humans and mice

Temperature and concentration calibration of aqueous polyvinylpyrrolidone (PVP) solutions for isotropic diffusion MRI phantoms

<div><p>To use the “apparent diffusion coefficient” (<i>D</i>_app) as a quantitative imaging parameter, well-suited test fluids are essential. In this study, the previously proposed aqueous solutions of polyvinylpyrrolidone (PVP) were examined and temperature calibrations were obtained. For example, at a temperature of 20°C, <i>D</i>_app ranged from 1.594 (95% CI: 1.593, 1.595) μm²/ms to 0.3326 (95% CI: 0. 3304, 0.3348) μm²/ms for PVP-concentrations ranging from 10% (w/w) to 50% (w/w) using K30 polymer lengths. The temperature dependence of <i>D</i>_app was found to be so strong that a negligence seems not advisable. The temperature dependence is descriptively modelled by an exponential function exp(<i>c</i>₂ (<i>T</i> − 20°<i>C</i>)) and the determined <i>c</i>₂ values are reported, which can be used for temperature calibration. For example, we find the value 0.02952 K^-1 for 30% (w/w) PVP-concentration and K30 polymer length. In general, aqueous PVP solutions were found to be suitable to produce easily applicable and reliable <i>D</i>_app-phantoms.</p></div

(double column): Images of the used phantom.

<p>a,b,c) High resolution images. d,e,f) Low resolution images. a,d) Signal images without diffusion weighting, i.e. with <i>b</i> = 0 s/mm². b,e) Signal image with <i>b</i> = 700 s/mm². Signal images are min-max normalized. c,f) <i>D</i>_app-maps of the phantom in units of μm²/ms. Cross sections of the volumes of interest are marked in blue in a and d.</p

(single column): Temperature calibration coefficient <i>c</i>₂ in dependence of PVP concentration for K30 and K90.

<p>Error bars denote 95% confidence intervals. The straight lines represent linear fits with weights inversely proportional to the width of the 95% confidence interval.</p

Recommended temperature calibration coefficient <i>c</i>₂ in K^-1.

<p>Recommended temperature calibration coefficient <i>c</i>₂ in K^-1.</p

Fit parameters describing the dependency of <i>D</i>_app on the temperature (see Eq (2)) for K90.

<p>95% confidence intervals are stated in brackets.</p