Homologous recombination repair (HRR) pathway deficiency (HRD) is involved in the tumorigenesis and progression of high-grade serous ovarian carcinoma (HGSOC) as well as in the sensitivity to platinum chemotherapy drugs. In this study, we obtained data from The Cancer Genome Atlas (TCGA) on HGSOC and identified scores for the loss of heterozygosity, telomeric allelic imbalance, and large-scale state transitions, and calculated the HRD score. We then investigated the relationships among the score, genetic/epigenetic alterations in HRR-related genes, and the clinical data. We found that BRCA1/2 mutations were enriched in the group with HRD scores ≥63. Compared with the groups with scores ≤62, this group had a good prognosis; we thus considered HRD scores ≥63 to be the best cutoff point for identifying HRD cases in HGSOC. Classification of HGSOC cases by the HRD status revealed a better prognosis for HRD cases caused by genetic alterations (genetic HRD) than those caused by epigenetic changes and those caused by undetermined reasons (p = 0.0002). Among cases without macroscopic residual tumors after primary debulking surgery, 11 of 12 genetic HRD cases survived after the median observation period of 6.6 years, showing remarkably high survival rates (p = 0.0059). In conclusion, HGSOC can be classified into subtypes with different prognoses according to HRD status. This classification could be useful for personalized HGSOC treatment.
AimOpen myomectomy (OM) was previously frequently performed; however, laparoscopic myomectomy (LM) has recently become more common. Nevertheless, myoma can recur after both LM and OM. In this study, we report our retrospective investigation of myoma recurrence by comparing LM and OM.MethodsA total of 474 patients underwent LM and 279 patients underwent OM. The patients were followed‐up postoperatively from six months to eight years. Recurrence was confirmed when a myoma with a diameter of ≥ 1 cm was detected. Post‐LM, post‐OM and cumulative recurrence rates were investigated, and a Cox hazard test was performed.ResultsThe cumulative recurrence rates between the two groups were 76.2% (LM) vs. 63.4% (OM) at eight years postoperatively. A log‐rank test revealed a significant difference between the two groups. Cox hazard testing revealed that LM, a larger number of enucleated myoma masses and the absence of postoperative gestation significantly contributed to the postoperative recurrence rate.ConclusionsLM yielded a higher recurrence rate than OM, likely a result of manual myoma removal in OM, which is a more exhaustive extraction of smaller myoma masses than performed in LM. In other words, fewer residual myoma masses after OM contribute to a lower postoperative recurrence rate.
We analyzed the intranuclear dynamics of estrogen receptor alpha (ER alpha) and progesterone receptor (PR)-A/B labeled with different spectral variants of green fluorescent protein (GFP) in living cells. The distribution of ER alpha and PR-A/B were changed from a diffuse to discrete pattern after the addition of both ligands, but the extent of discrete cluster formation of PR-A/B was lower than that of ER alpha. The nuclear areas where PR-A/B were accumulated were colocalized with the cluster of ER alpha, suggesting that cross-talk in the transcriptional regulation occurred in the loci. Fluorescence recovery after photobleaching (FRAP) analysis revealed that the mobility of PR-A/B was hastened by the coexistence of ER alpha, while the mobility of ER alpha was not changed by the coexistence of PR-A/B. Cluster formation was correlated with the nuclear matrix binding, because nuclear matrix binding capacity was also lower in PR-A/B than ER alpha. By ATP-depletion from the cells, most of ER alpha and PR-A/B were bound to the nuclear matrix and their mobilities were extinguished both in the absence and presence of ligand. Fluorescent protein (FP) tagged nuclear matrix component protein (NuMA), which was colocalized with ER alpha and PR-A/B, showed ATP-dependent rapid exchange in the nucleus. These results indicate that the mobility of ER alpha and PR-A/B is associated with the dynamics of the nuclear matrix.
MRI plays an essential role in patients before treatment for uterine mesenchymal malignancies. Although MRI includes methods such as diffusion-weighted imaging and dynamic contrast-enhanced MRI, the differentiation between uterine myoma and sarcoma always becomes problematic. The present paper discusses important findings to ensure that sarcomas are not overlooked in magnetic resonance (MR) images, and we describe the update in the differentiation between uterine leiomyoma and sarcoma with recent reports.
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