scholarly journals Expression of membrane type 1 matrix metalloproteinase (MMP-14) in epithelial ovarian cancer: High level expression in clear cell carcinoma

2009 ◽  
Vol 112 (2) ◽  
pp. 319-324 ◽  
Author(s):  
Brian P. Adley ◽  
Kara J. Gleason ◽  
Ximing J. Yang ◽  
M. Sharon Stack
2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5534-5534 ◽  
Author(s):  
John H. Farley ◽  
William E. Brady ◽  
Michael J. Birrer ◽  
David Marc Gershenson ◽  
Gini F. Fleming ◽  
...  

5534 Background: We examined disparities in prognosis between patients with ovarian clear cell carcinoma (OCCC) and serous epithelial ovarian cancer (SOC). Methods: Data from stage I-IV epithelial ovarian cancer (EOC) patients who participated in 12 randomized GOG protocols using platinum-based chemotherapy were reviewed. Proportional hazards models adjusted for age and stratified by protocol, treatment arm, stage, performance status (PS), and race were used to compare progression-free survival (PFS) and overall survival (OS) by cell type (clear cell versus serous). Results: There were 10,803 patients enrolled, 1272 were not eligible: leaving 9,531, of whom 544 (6%) had OCCC, 7,054 (74%) had SOC, and 1,933 (20%) had other; only the OCCC and SOC are considered here. OCCC were significantly younger, more often of Asian race, stage I, good PS, and optimally surgically debulked than SOC patients. Prior to adjustment, OCCC had better PFS and OS due to better prognostic factors. There was no significant difference in PFS or OS for early stage OCCC patients compared to high-grade (HG) SOC patients. For late stage patients, OCCC had poorer PFS and OS compared to SOC, OS HR= 1.66 (1.43, 1.91; p < 0.001). For both optimal, HR = 1.34 (1.10, 1.63; p = 0.003) and suboptimal, HR = 3.18 (2.13, 4.75; p < 0.001) OCCC had a significantly poorer OS than SOC. After adjusting for age and stratified by protocol and treatment arm, stage, performance status, and race, OCCC had a significantly decreased OS, HR= 1.53 (1.33,1.76; p < 0.001). In early stage cases, there was a significantly decreased treatment effect on PFS for consolidative therapy with weekly taxol versus observation in SOC compared to OCCC (p = 0.048). Conclusions: This is one of the largest analyses to date of OCCC treated in a uniform manner . OCCC patients have better PFS and OS compared to SOC; this, is due to their better prognostic factors. There was no observed difference in PFS or OS for early stage OCCC versus HGSOC. In late-stage patients, OCCC was significantly associated with decreased OS which was true for both optimal and suboptimally debulked patients. Finally, treatment effect was influenced by histology.


2019 ◽  
Vol 61 (7) ◽  
pp. 992-1000 ◽  
Author(s):  
Takafumi Ono ◽  
Keiko Kishimoto ◽  
Shinya Tajima ◽  
Ichiro Maeda ◽  
Masayuki Takagi ◽  
...  

Background Primary epithelial ovarian cancer is divided into several subtypes. The relationships between apparent diffusion coefficient (ADC) values and their subtypes have not yet been established. Purpose To investigate whether ADC values of epithelial ovarian cancer vary according to histologic tumor cellularity and evaluate the difference of clear cell carcinoma (CCC), high-grade serous carcinoma (HGSC), and endometrioid carcinoma (EC). Material and Methods This retrospective study included 51 cases of epithelial ovarian cancer (17 CCC, 20 HGSC, and 14 EC) identified by magnetic resonance imaging with pathological confirmation. All patients underwent diffusion-weighted imaging and the ADC values of lesions were measured. We counted the tumor cells in three high-power fields and calculated the average for each case. The Spearman’s correlation coefficient test was used to analyze correlation between ADC values and tumor cellularity. The ADC values of HGSC, EC, and CCC were compared using the Steel–Dwass test. Results The ADC values of all cases were significantly inversely correlated with tumor cellularity ( rs = −0.761; P < 0.001). The mean ± SD ADC values (×10−3 mm2/s) of CCC, HGSC, and EC were 1.24 ± 0.17 (range 0.98--1.65), 0.84 ± 0.10 (range 0.67--1.06), and 0.84 ± 0.10 (range 0.67--1.07). The mean ± SD tumor cellularity of CCC, HGSC, and EC was 162.88 ± 63.28 (range 90.33--305.67), 440.60 ± 119.86 (range 204.67--655.67), and 461.02 ± 81.86 (range 333.33--602.33). Conclusion There is a significant inverse correlation between ADC values and tumor cellularity in epithelial ovarian cancer. The mean ADC value of CCC was higher than those of HGSC and EC, seemingly due to the low cellularity of CCC.


2021 ◽  
Author(s):  
Kosuke Murakami ◽  
Akiko Kanto ◽  
Kazuko Sakai ◽  
Chiho Miyagawa ◽  
Hisamitsu Takaya ◽  
...  

AbstractRecent studies have reported cancer-associated mutations in normal endometrium. Mutations in eutopic endometrium may lead to endometriosis and endometriosis-associated ovarian cancer. We investigated PIK3CA mutations (PIK3CAm) for three hotspots (E542K, E545K, H1047R) in eutopic endometrium in patients with ovarian cancer and endometriosis from formalin-fixed paraffin-embedded specimens by laser-capture microdissection and droplet digital PCR. The presence of PIK3CAm in eutopic endometrial glands with mutant allele frequency ≥ 15% were as follows: ovarian clear cell carcinoma (OCCC) with PIK3CAm in tumors, 20/300 hotspots in 11/14 cases; OCCC without PIK3CAm, 42/78 hotspots in 11/12 cases; high-grade serous ovarian carcinoma, 8/45 hotspots in 3/5 cases; and endometriotic cysts, 5/63 hotspots in 5/6 cases. These rates were more frequent than in noncancer nonendometriosis controls (7/309 hotspots in 5/17 cases). In OCCC without PIK3CAm, 7/12 (58%) cases showed multiple hotspot mutations in the same eutopic endometrial glands. In 3/54 (5.6%) cases, PIK3CAm was found in eutopic endometrial stroma. Multisampling of the OCCC tumors with PIK3CAm showed intratumor heterogeneity in three of eight cases. In two cases, PIK3CAm was detected in the stromal component of the tumor. Homogenous PIK3CAm in the epithelial component of the tumor matched the mutation in eutopic endometrial glands in only one case. Eutopic endometrial glands in ovarian cancer and endometriosis show high frequency of PIK3CAm that is not consistent with tumors, and multiple hotspot mutations are often found in the same glands. While the mutations identified in eutopic endometrium may not be driver mutations in the patient’s cancer, these are still driver mutations but this specific clone has not undergone the requisite steps for the development of cancer.


2016 ◽  
Vol 68 (1) ◽  
pp. 155-163
Author(s):  
Xuan Wang ◽  
Yan Wang ◽  
Guichan Wang ◽  
Peishu Liu

Ovarian cancer is the leading cause of death from gynecologic cancer, reflecting its chemoresistance and frequent late diagnosis, and suggesting that a more effective treatment approach is needed. Lysyl oxidase (LOX) is involved in important biological processes such as gene regulation, cell signaling and cell motility, its deregulation contributing to tumor formation and development. Although it is known that LOX is involved in proliferation, migration and invasion in several types of tumors, studies of LOX in ovarian cancers are scarce. To explore the molecular regulation mechanisms in ovarian cancer tumorigenesis, the expression change and the function of LOX was confirmed in ovarian tissues and cells, which suggested that LOX is a tumor suppressor gene. To further understand how LOX expression is regulated in ovarian cancer, microRNAs(miRNAs) were considered because of their role in post-transcriptional regulation of many genes. Recent work has described differential expression of mature miRNAs in human cancers. Bioinformatics prediction which was used to find the appropriate miRNA regulating LOX, revealed that miR-29b regulates LOX protein level via its binding site on the 3'UTR of LOX mRNAin ES-2 cells, a human ovarian clear cell carcinoma cell line. miR-29b knockdown inhibited proliferation and invasion in ES-2 cells. Taken together, these findings suggest that influencing LOX regulation bychanging the level of miR-29b expression could provide a novel potential approachfor treating human ovarian clear cell carcinoma.


2020 ◽  
Author(s):  
Eric J. Devor ◽  
Jace R. Lapierre ◽  
Kimberly K. Leslie ◽  
David P. Bender

Abstract Objective: ES-2 ovarian cancer cells have long been reported to have originated from a primary clear cell carcinoma of the ovary presenting in a 47 year-old African American patient. Two recent publications have offered evidence calling both of these characteristics into question. Our objective was to further study this cell line using quantitative real-time PCR (qPCR) and mitochondrial DNA (mtDNA) sequencing in order to confirm or refute these inconsistencies.Results: qPCR assays on two characteristic loci, hepatocyte nuclear factor 1β (NHF-1β) and glutathione peroxidase 3 (GPX3), suggest that ES-2 are unusual clear cell carcinoma cells that appear more like high grade serous carcinoma than clear cell. Further, mtDNA haplotyping places the ancestral origin of the patient’s lineage in the Middle East or Europe and not Africa. These results are consistent with and support the conclusions of the two recent publications.


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