FS-C4BP (fully-sialylated alpha-chain of complement 4-binding protein) is a novel biomarker that can detect early stage epithelial ovarian cancer, especially clear cell carcinoma

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.

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Fully-sialylated alpha-chain of complement 4-binding protein: Diagnostic utility for ovarian clear cell carcinoma

Gynecologic Oncology ◽

10.1016/j.ygyno.2015.10.012 ◽

2015 ◽

Vol 139 (3) ◽

pp. 520-528 ◽

Cited By ~ 11

Author(s):

Mikio Mikami ◽

Kazuhiro Tanabe ◽

Koji Matsuo ◽

Yuko Miyazaki ◽

Masaki Miyazawa ◽

...

Keyword(s):

Cell Carcinoma ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Binding Protein ◽

Diagnostic Utility ◽

Ovarian Clear Cell Carcinoma ◽

Alpha Chain ◽

Complement 4

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Fully sialylated alpha-chain of complement 4–binding protein: Diagnostic utility for ovarian clear cell carcinoma

Gynecologic Oncology ◽

10.1016/j.ygyno.2016.04.092 ◽

2016 ◽

Vol 141 ◽

pp. 26

Author(s):

M. Mikami ◽

K. Tanabe ◽

K. Matsuo ◽

M. Miyazawa ◽

M. Hayashi ◽

...

Keyword(s):

Cell Carcinoma ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Binding Protein ◽

Diagnostic Utility ◽

Ovarian Clear Cell Carcinoma ◽

Alpha Chain ◽

Complement 4

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

Gynecologic Oncology ◽

10.1016/j.ygyno.2008.09.025 ◽

2009 ◽

Vol 112 (2) ◽

pp. 319-324 ◽

Cited By ~ 31

Author(s):

Brian P. Adley ◽

Kara J. Gleason ◽

Ximing J. Yang ◽

M. Sharon Stack

Keyword(s):

Ovarian Cancer ◽

Matrix Metalloproteinase ◽

Epithelial Ovarian Cancer ◽

Cell Carcinoma ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

High Level Expression ◽

Membrane Type ◽

High Level

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Apparent diffusion coefficient (ADC) values of serous, endometrioid, and clear cell carcinoma of the ovary: pathological correlation

Acta Radiologica ◽

10.1177/0284185119883392 ◽

2019 ◽

Vol 61 (7) ◽

pp. 992-1000 ◽

Cited By ~ 1

Author(s):

Takafumi Ono ◽

Keiko Kishimoto ◽

Shinya Tajima ◽

Ichiro Maeda ◽

Masayuki Takagi ◽

...

Keyword(s):

Ovarian Cancer ◽

Diffusion Coefficient ◽

Apparent Diffusion Coefficient ◽

Epithelial Ovarian Cancer ◽

Cell Carcinoma ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Apparent Diffusion ◽

Adc Values ◽

The Mean

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.

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Tatalaksana Radioterapi pada Kekambuhan Lokal Kanker Ovarium Clear Cell

Health & Medical Journal ◽

10.33854/heme.v1i2.240 ◽

2019 ◽

Vol 1 (2) ◽

pp. 44-49

Author(s):

Rhandyka Rafli

Keyword(s):

Ovarian Cancer ◽

Cell Carcinoma ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Early Stage ◽

Local Relapse ◽

Advanced Stage ◽

Tumor Residue ◽

Early Stage Ovarian Cancer

Clear Cell Carcinoma is a rare subtype of ovarian cancer. At early stage ovarian cancer were not exhibit symptoms, most of case were found at advanced stage. Treatments for advanced stage ovarian cancer are cytoreduction surgery and carboplatin and paclitaxel adjuvant chemotherapy. Cancer stem cells resilient and chemoresistants phenotype of clear cell carcinoma were responsible for local relapse. Radiotherapy with palliative intents can alleviate symptoms and increase quality of life, radiotherapy can also be given curatively for local relapse. Brachytherapy as dose escalation is recommended for limited and locally tumor residue.

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LncRNA CDKN2B-AS1 stabilized by IGF2BP3 drives the malignancy of renal clear cell carcinoma through epigenetically activating NUF2 transcription

Cell Death and Disease ◽

10.1038/s41419-021-03489-y ◽

2021 ◽

Vol 12 (2) ◽

Author(s):

Xina Xie ◽

Jiatian Lin ◽

Xiaoqin Fan ◽

Yuantang Zhong ◽

Yequn Chen ◽

...

Keyword(s):

Cell Carcinoma ◽

Survival Data ◽

Kinase Inhibitor ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Binding Protein ◽

Renal Clear Cell Carcinoma ◽

Receiver Operating Curve ◽

Migration And Invasion ◽

Integrated Analysis

AbstractBecause of the lack of sensitivity to radiotherapy and chemotherapy, therapeutic options for renal clear cell carcinoma (KIRC) are scarce. Long noncoding RNAs (lncRNAs) play crucial roles in the progression of cancer. However, their functional roles and upstream mechanisms in KIRC remain largely unknown. Exploring the functions of potential essential lncRNAs may lead to the discovery of novel targets for the diagnosis and treatment of KIRC. Here, according to the integrated analysis of RNA sequencing and survival data in TCGA-KIRC datasets, cyclin-dependent kinase inhibitor 2B antisense lncRNA (CDKN2B-AS1) was discovered to be the most upregulated among the 14 lncRNAs that were significantly overexpressed in KIRC and related to shorter survival. Functionally, CDKN2B-AS1 depletion suppressed cell proliferation, migration, and invasion both in vitro and in vivo. Mechanistically, CDKN2B-AS1 exerted its oncogenic activity by recruiting the CREB-binding protein and SET and MYND domain-containing 3 epigenetic-modifying complex to the promoter region of Ndc80 kinetochore complex component (NUF2), where it epigenetically activated NUF2 transcription by augmenting local H3K27ac and H3K4me3 modifications. Moreover, we also showed that CDKN2B-AS1 interacted with and was stabilized by insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), an oncofetal protein showing increased levels in KIRC. The Kaplan–Meier method and receiver operating curve analysis revealed that patients whose IGF2BP3, CDKN2B-AS1 and NUF2 are all elevated showed the shortest survival time, and the combined panel (containing IGF2BP3, CDKN2B-AS1, and NUF2) possessed the highest accuracy in discriminating high-risk from low-risk KIRC patients. Thus, we conclude that the stabilization of CDKN2B-AS1 by IGF2BP3 drives the malignancy of KIRC through epigenetically activating NUF2 transcription and that the IGF2BP3/CDKN2B-AS1/NUF2 axis may be an ideal prognostic and diagnostic biomarker and therapeutic target for KIRC.

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Frequent PIK3CA mutations in eutopic endometrium of patients with ovarian clear cell carcinoma

Modern Pathology ◽

10.1038/s41379-021-00861-3 ◽

2021 ◽

Author(s):

Kosuke Murakami ◽

Akiko Kanto ◽

Kazuko Sakai ◽

Chiho Miyagawa ◽

Hisamitsu Takaya ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Carcinoma ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Driver Mutations ◽

Intratumor Heterogeneity ◽

Ovarian Clear Cell Carcinoma ◽

Eutopic Endometrium ◽

Stromal Component ◽

Hotspot Mutations

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.

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