The Analysis of Cell Cycle–related Proteins in Ovarian Clear Cell Carcinoma Versus High-grade Serous Carcinoma

2018 ◽  
Vol 37 (6) ◽  
pp. 516-524 ◽  
Author(s):  
Yukiko Hazama ◽  
Takuya Moriya ◽  
Mika Sugihara ◽  
Rikiya Sano ◽  
Mitsuru Shiota ◽  
...  
2021 ◽  
Author(s):  
Wei Liu ◽  
Lin-Xue Qian ◽  
Xue-Jing wei

Abstract Purpose To investigate clinical and ultrasound features for differentiating ovarian clear cell carcinoma (OCCC) from ovarian high-grade serous carcinoma (HGSC). Methods Forty-five patients with OCCC and 72 patients with HGSC were retrospectively studied. Patient clinical characteristics and ultrasound features of tumors were evaluated. The differences, including laterality, menopausal status, Federation of Gynecology and Obstetrics (FIGO) stage between OCCC and HGSC patients were compared by Fisher’s exact test. The ultrasound features of tumors, including laterality, shape, configuration, color score, peritoneal implantation, and ascites, were evaluated and compared between the two groups. Results The average age at diagnosis in the OCCC group was 57.6±11.1 (range, 30–76) years, and 35.56% of patients were premenopausal. However, the average age at diagnosis was 63.4±12.2 (range, 42-81) years and 33.33% of patients were premenopausal in the HGSC group. There was a statistically significant difference in unilaterality (P< 0.001), clear boundaries (P<0.05), round or oval shape (P <0.05), and color score (P<0.05). Compared to HGSC patients, fewer OCCC patients had peritoneal implantation and ascites. There was a statistically significant difference in the mean size of papillary projections in OCCC and HGSC (P<0.05). The mean size of the papillary projections was significantly larger in OCCC than in HGSC. Conclusions OCCC commonly appeared as a large, round or oval mass with a clear boundary; the papillary projections of OCCC are larger and round. In contrast, HGSC was typically a large, irregular tumor with solid masses or mixed cystic-solid masses with small papillary projections.


2019 ◽  
Vol 20 (18) ◽  
pp. 4330 ◽  
Author(s):  
Saya Nagasawa ◽  
Kazuhiro Ikeda ◽  
Kuniko Horie-Inoue ◽  
Sho Sato ◽  
Atsuo Itakura ◽  
...  

Objective: Ovarian cancer has the highest mortality among gynecological cancers. High-grade serous carcinoma (HGSC) is the most common histotype of ovarian cancer regardless of ethnicity, whereas clear cell carcinoma (CCC) is more common in East Asians than Caucasians. The elucidation of predominant signaling pathways in these cancers is the first step towards understanding their molecular mechanisms and developing their clinical management. Methods: RNA sequencing was performed for 27 clinical ovarian specimens from Japanese women. Principal component analysis (PCA) was conducted on the sequence data mapped on RefSeq with normalized read counts, and functional annotation analysis was performed on genes with substantial weights in PCA. Knockdown experiments were conducted on the selected genes on the basis of PCA. Results: Functional annotation analysis of PCA-defined genes showed predominant pathways, such as cell growth regulators and blood coagulators in CCC and transcription regulators in HGSC. Knockdown experiments showed that the inhibition of the calcium-dependent protein copine 8 (CPNE8) and the transcription factor basic helix-loop-helix family member e 41 (BHLHE41) repressed the proliferation of CCC- and HGSC-derived cells, respectively. Conclusions: This study identified CPNE8 and BHLHE41 as characteristic genes for CCC and HGSC, respectively. The systemic identification of differentially expressed genes in CCC and HGSC will provide useful information to understand transcriptomic differences in these ovarian cancers and to further develop potential diagnostic and therapeutic options for advanced disease.


2018 ◽  
Vol 28 (9) ◽  
pp. 1812-1820 ◽  
Author(s):  
Menghan Zhu ◽  
Nan Jia ◽  
Yanyan Nie ◽  
Jun Chen ◽  
Yahui Jiang ◽  
...  

ObjectiveHigh-risk endometrial cancers (ECs), including high-grade EC, serous carcinoma (SC), clear cell carcinoma, and carcinosarcoma, account for 50% of deaths due to ECs. Therapies for these cancers are limited, and patient-derived tumor xenograft (PDTX) models are useful tools for preclinical drug evaluation, biomarker identification, and personalized medicine strategies. Here, we used and compared 2 methods to establish PDTX models.MethodsFresh tumor tissues collected from 18 primary high-risk EC patients (10 high-grade ECs, 6 SCs, 1 clear cell carcinoma, and 1 carcinosarcoma) were engrafted subcutaneously and in the subrenal capsule in NOD/SCID for establishment and Balb/c-nu/nu mice for expansion. Histology and cytokeratin, estrogen receptor, progesterone receptor, and P53 expression were evaluated to assess the similarity of primary tumors and different generations of PDTX tumors. Whole-exome sequencing (WES) and RNA sequencing were used in 2 high-grade EC models to verify whether the genetic mutation profiles and gene expression were similar between primary and PDTX tumors.ResultsThe total tumor engraftment rate was 77.8% (14/18) regardless of the engraft method. The tumor engraftment rate was increased in subrenal capsule models compared with subcutaneous models (62.5% vs 50%, P = 0.464). The time to tumor formation varied significantly from 2 to 11 weeks. After subrenal capsular grafting, grafted tumors could be successfully transplanted to subcutaneous sites. We observed good similarity between primary tumors and corresponding different passages of xenografts.ConclusionsThe combination of 2 engrafting methods increases the tumor engraftment rate. The high tumor engraftment rate ensures the establishment of a high-risk EC biobank, which is a powerful resource for performing preclinical drug-sensitivity tests and identifying biomarkers for response or resistance.


Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1769
Author(s):  
Kazuaki Takahashi ◽  
Masataka Takenaka ◽  
Aikou Okamoto ◽  
David D. L. Bowtell ◽  
Takashi Kohno

Ovarian clear cell carcinoma (OCCC) is a histological subtype of ovarian cancer that is more frequent in Asian countries (~25% of ovarian cancers) than in US/European countries (less than 10%). OCCC is refractory to conventional platinum-based chemotherapy, which is effective against high-grade serous carcinoma (HGSC), a major histological subtype of ovarian cancer. Notably, deleterious mutations in SWI/SNF chromatin remodeling genes, such as ARID1A, are common in OCCC but rare in HGSC. Because this complex regulates multiple cellular processes, including transcription and DNA repair, molecularly targeted therapies that exploit the consequences of SWI/SNF deficiency may have clinical efficacy against OCCC. Three such strategies have been proposed to date: prioritizing a gemcitabine-based chemotherapeutic regimen, synthetic lethal therapy targeting vulnerabilities conferred by SWI/SNF deficiency, and immune checkpoint blockade therapy that exploits the high mutational burden of ARID1A-deficient tumor. Thus, ARID1A deficiency has potential as a biomarker for precision medicine of ovarian cancer.


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