Background: Within the claudin (CLDN) family, CLDN12 mRNA expression is altered in various types of cancer, but its clinicopathological relevance has yet to be established due to the absence of specific antibodies (Abs) with broad applications. Methods: We generated a monoclonal Ab (mAb) against human/mouse CLDN12 and verified its specificity. By performing immunohistochemical staining and semiquantification, we evaluated the relationship between CLDN12 expression and clinicopathological parameters in tissues from 138 cases of cervical cancer. Results: Western blot and immunohistochemical analyses revealed that the established mAb selectively recognized the CLDN12 protein. Twenty six of the 138 cases (18.8%) showed low CLDN12 expression, and the disease-specific survival (DSS) and recurrence-free survival rates were significantly decreased compared with those in the high CLDN12 expression group. We also demonstrated, via univariable and multivariable analyses, that the low CLDN12 expression represents a significant prognostic factor for the DSS of cervical cancer patients (HR 3.412, p = 0.002 and HR 2.615, p = 0.029, respectively). Conclusions: It can be concluded that a reduced CLDN12 expression predicts a poor outcome for cervical cancer. The novel anti-CLDN12 mAb could be a valuable tool to evaluate the biological relevance of the CLDN12 expression in diverse cancer types and other diseases.

Hereditary cancer syndromes, which are characterized by onset at an early age and an increased risk of developing certain tumors, are caused by germline pathogenic variants in tumor suppressor genes and are mostly inherited in an autosomal dominant manner. Therefore, hereditary cancer syndromes have been used as powerful models to identify and characterize susceptibility genes associated with cancer. Furthermore, clarification of the association between genotypes and phenotypes in one disease has provided insights into the etiology of other seemingly different diseases. Molecular genetic discoveries from the study of hereditary cancer syndrome have not only changed the methods of diagnosis and management, but have also shed light on the molecular regulatory pathways that are important in the development and treatment of sporadic tumors. The main cancer susceptibility syndromes that involve gynecologic cancers include hereditary breast and ovarian cancer syndrome as well as Lynch syndrome. However, in addition to these two hereditary cancer syndromes, there are several other hereditary syndromes associated with gynecologic cancers. In the present review, we provide an overview of the clinical features, and discuss the molecular genetics, of four rare hereditary gynecological cancer syndromes; Cowden syndrome, Peutz-Jeghers syndrome, DICER1 syndrome and rhabdoid tumor predisposition syndrome 2.

This study aimed to clarify the association between uterine myomas and preterm birth (PTB), preterm premature rupture of membranes (pPROM), and intrauterine infection (II). The study was based on data from the Japan Environment and Children’s Study, a nationwide birth-cohort study. Data of 86,370 women with singleton births after 22 weeks of gestation (with uterine myomas, n = 5354) were retrospectively analyzed. Using logistic regression, adjusted odds ratios (aORs) for PTB, pPROM, and II were calculated considering women without uterine myomas as the reference. Additionally, the effects of II on the incidence of PTB and pPROM were evaluated. In women with uterine myomas, the aORs for PTB before 37 and 34 weeks, pPROM, and II were 1.37 (95% confidence interval, 1.22–1.54), 1.61 (1.27–2.05), 1.65 (1.33–2.04), and 1.05 (0.75–1.46), respectively. The aORs for PTB and pPROM in women with II and uterine myomas were not significantly increased. Uterine myomas during pregnancy were associated with an increased incidence of PTB and pPROM. However, II in women with uterine myomas was not associated with an increased incidence of PTB or pPROM. These findings suggest a potential risk of occult PTB in pregnant women with uterine myomas.

NTRK gene fusion is rare in gynecological cancer. Entrectinib is a novel targeted drug, which is a potent inhibitor of TRK A, B and C. The present case report described a case of recurrent ovarian cancer with TPM3‑NTRK1 rearrangement, which was detected by next‑generation sequencing (NGS) and treated with entrectinib. A 56‑year‑old woman was diagnosed as having stage IV ovarian cancer with positive pleural fluid cytology. Neoadjuvant chemotherapy and interval debulking surgery, followed by chemotherapy, were performed. A total of 10 months after completion of chemotherapy, the disease recurred and the patient was treated with multimodal therapy for recurrence. DNA‑based NGS detected TPM3‑NTRK1 rearrangement and entrectinib therapy was initiated; however, the disease progressed despite 6 weeks of entrectinib administration, and 1 month after discontinuation of entrectinib, the patient died. After their death, immunohistochemistry with a pan‑Trk monoclonal antibody was performed to determine the expression levels of TRK; however, immunohistochemistry was negative for TRK. In conclusion, the present case report described a rare case of recurrent ovarian cancer with TPM3‑NTRK1 gene fusion, in which entrectinib was not effective. While NTRK gene fusion was detected by DNA‑based NGS, immunohistochemistry was negative for TRK. These findings indicated that immunohistochemistry may be required for confirmation of TRK protein expression prior to entrectinib administration.

The association of maternal preconception dysmenorrhea, especially primary dysmenorrhea, with obstetric complications has not been clearly described. Therefore, we evaluated the association of preconception dysmenorrhea with obstetric complications while accounting for the presence of pelvic pathologies. We analyzed the data of women with singleton live births at and after 22 weeks of gestation enrolled in the Japan Environment and Children’s Study, a nationwide birth cohort study, between 2011 and 2014. Participants with psychological disorders were excluded. Preconception dysmenorrhea, identified in the medical record transcripts, was categorized into mild dysmenorrhea (MD) and severe dysmenorrhea (SD). Furthermore, excluding those who had pelvic pathologies via self-reported questionnaires (endometriosis, adenomyosis, and uterine myomas) with MD and SD, preconception dysmenorrhea was categorized into mild primary dysmenorrhea (MPD) and severe primary dysmenorrhea (SPD), respectively. Using multiple logistic regression, adjusted odds ratios (aORs) for obstetric complications, including preterm birth (PTB) before 37 weeks and 34 weeks, small-for-gestational-age infants, preterm premature rupture of membrane, and hypertensive disorders of pregnancy, were calculated (considering confounders) in women with (1) MD or SD and (2) MPD or SPD. Women without preconception dysmenorrhea were used as a reference. A total of 80,242 participants were analyzed. In women with SD, the aOR for PTB before 37 weeks was 1.38 (95% confidence interval [CI] 1.10, 1.72). In women with SPD, the aOR for PTB before 37 weeks was 1.32 (95% CI 1.02, 1.71). There was no association between women with MD or MPD and obstetric complications. SD and SPD are significantly associated with an increased incidence of PTB before 37 weeks. Care providers should provide proper counseling regarding the association between preconception dysmenorrhea and obstetric complications. Optimal management of pregnant women with preconception dysmenorrhea to reduce the incidence of PTB should be elucidated in further studies, with detailed clinical data of pelvic pathologies.

Previous studies have demonstrated the benefit of radiation therapy for patients with recurrent epithelial ovarian cancer; however, the effects of proton beam therapy in these patients remain unelucidated. This study aimed to evaluate the use of proton beam therapy in recurrent epithelial ovarian cancer and to identify factors predictive of local control. This retrospective study included 13 patients with a total of 30 lesions who underwent proton beam therapy for recurrent epithelial ovarian cancer at our institution between October 2008 and March 2021. The median age of the patients at the initial proton beam therapy was 62 (range, 42–82) years. Eight patients had stage III or IV disease, and seven had serous carcinoma; ten patients exhibited platinum resistance. The irradiated sites included 16 lymph nodes and 9 pelvic or abdominal masses. The median tumor size and maximum standardized uptake value (SUVmax) of fluorine-18-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) were 25 (range, 9–83) mm and 12.6 (range, 3.9–25.1), respectively. The median total dose was 65 (range, 45–72) Gy (relative biological effectiveness). The 1- and 2-year local control were 91.5% and 71.3%, respectively. The SUVmax of 18F-FDG-PET/CT was a significant predictor of local control (cutoff value, 17.7). The median progressing-free and overall survival after proton beam therapy initiation were 9.6 and 21.5 months, respectively. No grade 3 or higher proton beam therapy-induced adverse events were observed. Proton beam therapy demonstrated excellent local control of recurrent epithelial ovarian cancer, with tolerable toxicity, suggesting that this modality may represent a promising treatment option. The SUVmax of 18F-FDG-PET/CT performed prior to proton beam therapy may serve as a predictor of local control. Not applicable.