Objective: To clarify the frequency of deficient mismatch repair (dMMR) in Japanese ovarian cancer patients, we examined microsatellite instability (MSI) status and immunohistochemistry (IHC) subtypes, including endometrioid carcinoma (EMC), clear cell carcinoma (CCC), or a mixture of both (Mix). Methods: We registered 390 patients who were diagnosed with EMC/CCC/Mix between 2006 and 2015 and treated at seven participating facilities. For 339 patients confirmed eligible by the Central Pathological Review Board, MSI, IHC, and MutL homolog 1 methylation analyses were conducted. The tissues of patients with Lynch syndrome (LS)-related cancer histories, such as colorectal and endometrial cancer, were also investigated. Results: MSI-high (MSI-H) status was observed in 2/217 CCC (0.9%), 10/115 EMC (8.7%), and 1/4 Mix (25%). Additionally, loss of MMR protein expression (LoE-MMR) was observed in 5/219 (2.3%), 16/115 (14.0%), and 1/4 (25%) patients with CCC, EMC, and Mix, respectively. Both MSI-H and LoE-MMR were found significantly more often in EMC (p<0.001). The median (range) ages of patients with MMR expression and LoE-MMR were 54 (30–90) and 46 (22–76) (p=0.002), respectively. In the multivariate analysis, advanced stage and histological type were identified as prognostic factors. Conclusion The dMMR rate for EMC/CCC was similar to that reported in Western countries. In Japan, it is assumed that the dMMR frequency is higher because of the increased proportion of CCC.

The previous study has shown that repeated D domain-like (Rdd) proteins, a group of novel secretory proteins consisting of repeated domains of a cysteine-rich sequence, are involved in the process of blood vessel formation in Xenopus embryo. We performed further experiments to examine the localization of Rdd proteins in embryogenesis. Detection of tagged Rdd proteins expressed in blastomeres showed that Rdd proteins formed a high molecular weight complex and existed in the extracellular space. A rabbit antibody against the Rdd synthetic peptide identified a single band of 28 kD in embryonic tissue extract. By whole-mount immunostaining analysis, signal was detected in the regions of inter-somites, vitelline veins, and branchial arches at the tailbud stage. Staining of Rdd was remarkably reduced in the embryos injected with vascular endothelial growth factor Morpholino. We suggest that Rdd proteins interact with a molecule(s) associated with vascular precursor cells.
Blastomeres ; Blood Vessels ; Branchial Region ; Embryonic Development ; Embryonic Structures* ; Extracellular Space ; Female ; Molecular Weight ; Pregnancy ; Vascular Endothelial Growth Factor A ; Veins ; Vitellins ; Xenopus*