Xin Lu

Precision Diagnosis and Individualized Therapy of Non‐Gestational Choriocarcinoma Invading the Corpus Uteri and Cervix: A Case Report and Literature Review

ABSTRACT Background Non‐gestational choriocarcinoma (NGCC) is a rare type of malignant tumor. Primary lesions are typically detected in the ovary and rarely invade the corpus uteri and cervix. NGCC usually has a poor prognosis due to the difficulty in achieving early and accurate diagnoses because of its rarity. Case This case described a female who was initially diagnosed with gestational choriocarcinoma and treated with EMA‐CO chemotherapy. However, subsequent short tandem repeat (STR) analysis confirmed the diagnosis as NGCC, prompting surgical intervention. Given her favorable response and after thorough communication, three additional cycles of EMA‐CO chemotherapy were recommended. At her last follow‐up, her human chorionic gonadotropin level had normalized. Conclusion This case presents a rare instance of NGCC with simultaneous uterine and cervical involvement, confirmed by STR analysis and successfully managed with the EMA‐CO regime. It highlights the necessity of precise diagnosis and personalized treatment for effective management of this disease.

The epigenetic factor CHD4 contributes to metastasis by regulating the EZH2/β-catenin axis and acts as a therapeutic target in ovarian cancer

Abstract Background The overall survival rate of patients with advanced ovarian cancer (OC) has remained static for several decades. Advanced ovarian cancer is known for its poor prognosis due to extensive metastasis. Epigenetic alterations contribute to tumour progression and therefore are of interest for potential therapeutic strategies. Methods Following our previous study, we identified that CHD4, a chromatin remodelling factor, plays a strong role in ovarian cancer cell metastasis. We investigated the clinical significance of CHD4 through TCGA and GEO database analyses and explored the effect of CHD4 expression modulation and romidepsin treatment on the biological behaviour of ovarian cancer through CCK-8 and transwell assays. Bioluminescence imaging of tumours in xenografted mice was applied to determine the therapeutic effect of romidepsin. GSEA and western blotting were used to screen the regulatory mechanism of CHD4. Results In ovarian cancer patient specimens, high CHD4 expression was associated with a poor prognosis. Loss of function of CHD4 in ovarian cancer cells induced suppression of migration and invasion. Mechanistically, CHD4 knockdown suppressed the expression of EZH2 and the nuclear accumulation of β-catenin. CHD4 also suppressed the metastasis of ovarian cancer cells and prevented disease progression in a mouse model. To inhibit the functions of CHD4 that are mediated by histone deacetylase, we evaluated the effect of the HDAC1/2 selective inhibitor romidepsin. Our findings indicated that treatment with romidepsin suppressed the progression of metastases in vitro and in vivo. Conclusions Collectively, our results uncovered an oncogenic function of CHD4 in ovarian cancer and provide a rationale for clinical trials of romidepsin in ovarian cancer patients.

The individualized significance of lymphadenectomy across all age groups and histologies in malignant ovarian germ cell tumors

To evaluate the therapeutic role of lymphadenectomy on patients with malignant ovarian germ cell tumor (MOGCT) and to investigate the risk factors of lymph node metastasis. Patients of MOGCT between 1988 and 2013 with definite lymph node information were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Survival curves were estimated using the Kaplan-Meier method, and Cox regression analyses were performed to evaluate the effects of clinical and pathologic variables on survival. 2424 MOGCT patients with information on lymph nodes were included. Of the entire cohort, 46.2% patients received lymphadenectomy. The most common (42.2%) histologic type was teratoma, and 70.6% patients had FIGO stage I disease. Cox proportional model verified that age, grade, and log odds of positive lymph nodes (LODDS) were independent prognostic factors. Subgroup analysis showed that the association between the lymph node resection and better survival in the different age cohort. Lymphadenectomy is not recommended for children (0-14 years). For patients 40 years of age and older, and for those who have the dysgerminoma type or endodermal sinus type, lymphadenectomy had an outstanding therapeutic role. As a parameter to assess lymph node status, LODDS could be used to classify MOGCTs.

Clinicopathological Characteristics and Prognosis of 91 Patients with Seromucinous and Mucinous Borderline Ovarian Tumors: a Comparative Study

To explore the differences in clinicopathological characteristics and prognosis between seromucinous borderline ovarian tumors (SMBOTs) and mucinous borderline ovarian tumors (MBOTs). Ninety-one patients with SMBOTs and MBOTs who underwent surgery at the Obstetrics and Gynecology Hospital of Fudan University from July 2006 to January 2015 were included. The median onset age of patients with SMBOTs (29 years, 20-77) was younger than that of patients with MBOTs (37 years, 16-71). SMBOTs were more likely to be exogenous and show bilateral ovarian involvement and had a smaller average tumor size of 10.63 cm, while MBOTs were more prone to endogenous growth and show unilateral involvement and had a larger average tumor size of 18.55 cm (p < 0.05). Compared with MBOTs, SMBOTs were characterized by the expression of Mullerian differentiation markers (p < 0.05). Recurrence occurred in 15.8% patients with SMBOT and 9.1% patients with MBOT. One case of SMBOT (2.6%) and one case of MBOT (2.3%) progressed to malignancy during follow-up, but no disease-related death was observed. Age less than 40 years was a risk factor for recurrence, while the effect of fertility-sparing surgery (FSS) on recurrence requires a larger sample size to be validated. The clinical characteristics of SMBOTs and MBOTs are similar but also quite different. High expression of Mullerian differentiation markers in SMBOT may indicate a better response to hormone therapy. Repeated FSS should be performed with caution and fully informed because of the risk of recurrence and progression to malignancy.

Mucinous borderline ovarian tumors with and without Intraepithelial Carcinoma: Differences in clinicopathologic features and fertility results

AbstractAimTo investigate the clinicopathologic characteristic and fertility results of patients with mucinous borderline ovarian tumors (MBOTs), and the effects of intraepithelial carcinoma (IECA) on them.MethodsFifty‐two patients treated for MBOTs with or without IECA were retrospectively analyzed.ResultsPatients with IECA were more frequently observed at stage Ic (3/12 vs 1/40, P = 0.034) and accompanied by microinvasive carcinoma (3/12 vs 1/40, P = 0.034). The detected rate of IECA by intraoperative frozen section (5/12, 41.7%) was much lower than that of MBOTs (82.5%, P = 0.010). About 61.5% patients in our study underwent fertility‐sparing surgery. Follow‐up information was retained completely in 41 patients. And all four tumor recurrences were observed (9.8%) in conservative surgery group in 66 months, though there was no statistical association (P = 0.280). There were three patients who recurred more than once, even one occurred tumor‐related death. Only one recurrent patient was in IECA group (P &gt; 0.05). However, patients with IECA were more likely to receive adjuvant chemotherapy (3 of 12 vs 0 of 40, P = 0.010) and surgical staging (75% vs 52.5%, P = 0.200). As for fertility results, nine patients wished to be pregnant and seven of them (77.8%) were successful.ConclusionFor young patients with MBOTs, fertility results are satisfactory after conservative surgery. But patients should be fully informed about the relative high recurrent rate. And IECA has no statistical negative effects on MBOTs till now, but a long‐term follow‐up is required.

Bevacizumab confers significant improvements in survival for ovarian cancer patients with low miR-25 expression and high miR-142 expression

Abstract Background Lymphovascular space invasion (LVSI) is the first step of hematogenous metastasis. Exploration of the differential miRNA expression profiles between LVSI-positive and LVSI-negative ovarian cancer tissues may help to identify key miRNAs involved in the hematogenous metastasis of ovarian cancer. This study is aimed to identify microRNAs (miRNAs) that are differentially expressed between LVSI-positive and LVSI-negative ovarian cancer tissues, followed by exploring their association with bevacizumab response in ovarian cancer patients. Methods The Cancer Genome Altas (TGGA) dataset was used to identify the differentially expressed miRNAs between LVSI-positive and LVSI-negative ovarian cancer tissues. The prognostic value of the differentially expressed miRNAs was determined using GSE140082 dataset. Results We showed that miR-25 and miR-142 were differentially expressed between LVSI-positive and LVSI-negative ovarian cancer tumors. Kaplan-Meier analysis indicated that high miR-25 expression was associated with increased progression free survival (PFS) and extended overall survival (OS). Moreover, patients with low miR-25 expression benefited significantly from bevacizumab treatment in terms of PFS. A similar trend was observed in terms of OS though without reaching statistical significance. In contrast, no significant survival benefits from bevacizumab were observed in patients with high miR-25 expression in terms of PFS and OS. There was no significant correlation between miR-142 expression and PFS. In contrast, high miR-142 expression was associated with reduced OS. Moreover, patients with high miR-142 expression benefited significantly from bevacizumab treatment in terms of PFS and OS. However, bevacizumab treatment conferred no significant improvements in both PFS and OS in patients with low miR-142 expression. The nomogram for PFS indicated that miR-25 expression had a larger contribution to PFS than debulking status and bevacizumab treatment. And the nomogram for OS illustrated both miR-25 expression and miR-142 expression as sharing a larger contribution to OS than bevacizumab treatment and debulking status. Conclusion In conclusion, miR-25 expression correlates with a better PFS and OS in ovarian cancer. Patients with low miR-25 expression and high miR-142 expression could benefit from bevacizumab treatment significantly.

DNA methylation-based profiling reveals distinct clusters with survival heterogeneity in high-grade serous ovarian cancer

AbstractHigh-grade serous ovarian cancer (HGSOC) is the most common type of epigenetically heterogeneous ovarian cancer. Methylation typing has previously been used in many tumour types but not in HGSOC. Methylation typing in HGSOC may promote the development of personalized care. The present study used DNA methylation data from The Cancer Genome Atlas database and identified four unique methylation subtypes of HGSOC. With the poorest prognosis and high frequency of residual tumours, cluster 4 featured hypermethylation of a panel of genes, which indicates that demethylation agents may be tested in this group and that neoadjuvant chemotherapy may be used to reduce the possibility of residual lesions. Cluster 1 and cluster 2 were significantly associated with metastasis genes and metabolic disorders, respectively. Two feature CpG sites, cg24673765 and cg25574024, were obtained through Cox proportional hazards model analysis of the CpG sites. Based on the methylation level of the two CpG sites, the samples were classified into high- and low-risk groups to identify the prognostic information. Similar results were obtained in the validation set. Taken together, these results explain the epigenetic heterogeneity of HGSOC and provide guidance to clinicians for the prognosis of HGSOC based on DNA methylation sites.