Takahiro Nozaki

Clinical and molecular biomarkers predicting response to PARP inhibitors in ovarian cancer

To determine the useful biomarker for predicting the effects of poly-(ADP ribose)-polymerase (PARP) inhibitors in Japanese patients with ovarian cancer. We collected clinical information and performed molecular biological analysis on 42 patients with ovarian, fallopian tube, and primary peritoneal carcinomas who received PARP inhibitors. Among the analyzed patients with ovarian cancer, 23.8% had germline We found that HRRm can be a useful biomarker for predicting the effects of PARP inhibitors in treating ovarian cancer and that the PFI can also be useful in recurrent ovarian cancer.

Elucidation of genomic origin of synchronous endometrial and ovarian cancer (SEO) by genomic and microsatellite analysis

Elucidation of clonal origin of synchronous endometrial and ovarian cancers (SEOs). We reviewed 852 patients who diagnosed endometrial and/or ovarian cancer. Forty-five (5.3%) patients were diagnosed as SEOs. We evaluated blood and tissue samples from 17 patients. We analyzed the clonal origins of 41 samples from 17 patients by gene sequencing, mismatch microsatellite instability (MSI) polymerase chain reaction assay and immunohistochemical (IHC) staining of 4 repair genes. Sixteen of 17 patients had at least 2 or more trunk mutations shared between endometrial and ovarian cancer suggesting the identical clonal origins. The shared trunk mutation are frequently found in endometrial cancer of the uterus, suggesting the uterine primary. Four out of 17 (24%) SEOs had mismatch repair (MMR) protein deficiency and MSI-high (MSI-H) states. One case was an endometrial carcinoma with local loss of MSH6 protein expression by IHC staining, and the result of MSI analysis using the whole formalin-fixed, paraffin-embedded specimen was microsatellite stable. In contrast, ovarian tissue was deficient MMR and MSI-H in the whole specimen. This indicated that MMR protein deficiency could occur during the progression of disease. Most SEOs are likely to be a single tumor with metastasis instead of double primaries, and their origin could be endometrium. In addition, SEOs have a high frequency of MMR gene abnormalities. These findings not only can support the notion of uterine primary, but also can help to expect the benefit for patients with SEOs by immuno-oncology treatment.

Optimizing arm placement in the Hugo™ RAS system-based hysterectomy: development and validation of a simplified “Narrow setting” approach

We aimed to determine the usefulness of the new setup, the "Narrow setting," by examining our initial experience with the Hugo

Molecular analysis of ascitic fluid cytology reflects genetic changes of malignancies of the ovary equivalent to surgically resected specimens

BACKGROUNDThe objective of this study was to identify the clinical utility of genomic analysis of ascitic fluid cytology (AC) in patients with epithelial ovarian cancer.METHODSTargeted next‐generation sequencing was used to analyze 66 samples from 33 patients who had ovarian (n = 23), fallopian tube (n = 2), and peritoneal (n = 8) carcinoma, and the concordance rate of molecular profiles was compared between surgically resected, formalin‐fixed, paraffin‐embedded (FFPE) tissues and AC samples.RESULTSIn total, 159 mutations were identified (54 oncogenic mutations and 105 nononcogenic mutations) in 66 DNA samples (33 FFPE tissues and 33 AC samples) from 33 patients. Of the 159 mutations, 57 (35.8%) were shared between surgically resected FFPE tissues and AC samples. However, the concordance rate of the molecular profiles between the 2 was significantly higher for oncogenic mutations compared with nononcogenic mutations (85.1% vs 10.5%; P < .01). Indeed, the AC samples covered all oncogenic mutations (n = 46) that were detected in surgically resected specimens and identified additional mutations (n = 8).CONCLUSIONSThe current results indicated that genomic analysis of AC can identify all of the genetic changes associated with epithelial ovarian cancer to understand tumor characteristics without interventional surgery or biopsy and may play an important role in developing personalized precision medicine.