Low expression of gamma-glutamyl transpeptidase 1 is an independent poor prognostic factor in ovarian clear cell carcinoma, in relation to up-regulation of immune suppressive genes and EMT-related genes.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6042-6042
Author(s):  
Hiroshi Asano ◽  
Ryosuke Matsuoka ◽  
Kanako C Hatanaka ◽  
Daisuke Endo ◽  
Ayako Nozaki ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factor ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Ovarian Clear Cell Carcinoma ◽  
Poor Prognostic Factor ◽  
Gsh Metabolism ◽  
Low Expression

6042 Background: Ovarian clear cell carcinoma (OCCC) is a distinct entity from other epithelial ovarian cancers such as the most prevalent high-grade serous cancer (HGSC), and often exhibit less sensitivity to platinum-based chemotherapy. Several studies using cell lines have reported that glutathione (GSH) metabolism plays an important role in chemo-resistance of OCCC. Here, we aimed to correlate the prognosis of OCCC and the expression of gamma-glutamyltransferase 1 (GGT1), one of the key enzymes in GSH metabolism. Methods: We prepared a FFPE-tissue microarray, and analyzed 56 OCCC patients with the follow-up periods over 3 years. Expression level of GGT1 was evaluated by immunohistochemistry (IHC) using H-score (0-300), and was correlated with clinical outcomes. The prognostic significance was assessed by multivariate analysis using Cox regression model. To investigate the possible related pathways, we performed transcriptome analysis using Ion AmpliSeq Transcriptome Human Gene Expression Kit (Thermo Fisher Scientific) from the frozen tissue specimens collected from 33 ovarian cancer patients including 15 OCCC patients and 18 HGSC patients. Results: The OCCC patients were divided into two populations in the histogram of H-score in IHC staining, and the cut-off value was 90; 44 cases showed GGT1-high, and remaining 12 cases were GGT1-low. Follow-up periods, FIGO stage, and optimal surgery rate were not significantly different between two groups. However, platinum-resistant recurrent rate was significantly higher (42% vs. 14%, p=0.027), and overall survival (OS) was significantly shorter (5-year OS; 42% vs. 72%, p=0.0226) in GGT1-low OCCC. Multivariate analysis revealed that low expression of GGT1 was one of the independent poor prognostic factors as well as platinum-drug resistance. In enrichment analysis, the genes related to GSH metabolism, such as SLC3A1, GGT1, CSE, and GPX3 were up-regulated and positively correlated with HNF1B expression in OCCC. The expression level of GGT1 was inversely correlated with that of immune suppressive genes (TGF-b, IFNG, IL10, FOXP3, PD-L1, CTLA4) and epithelial-mesenchymal transition (EMT)-related genes (CDH2, VIM, TWIST1, ZEB1, ZEB2) in OCCC samples. Conclusions: Low expression of GGT1 is an independent poor prognostic factor probably in part due to suppression of tumor immunity and induction of EMT in OCCC.

PIK3CA overexpression is a possible prognostic factor for favorable survival in ovarian clear cell carcinoma

2013 ◽  
Vol 44 (2) ◽  
pp. 199-207 ◽  
Author(s):  
Azusa Abe ◽  
Takeo Minaguchi ◽  
Hiroyuki Ochi ◽  
Mamiko Onuki ◽  
Satoshi Okada ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Ovarian Clear Cell Carcinoma

scholarly journals Serum D-dimer, Albumin and Systemic Inflammatory Response Markers in Ovarian Clear Cell Carcinoma and Their Prognostic Implications

2020 ◽  
Author(s):  
Wei Chen ◽  
Siyuan Zhong ◽  
Boer Shan ◽  
Shuling Zhou ◽  
Xiaohua Wu ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Inflammatory Response ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Systemic Inflammatory Response ◽  
Ca 125 ◽  
Chemotherapy Response ◽  
Ovarian Clear Cell Carcinoma ◽  
D Dimer

Abstract Background: This study attempts to evaluate whether preoperative systemic inflammatory response (SIR) markers or other hematological variables, such as albumin, D-dimer, and carbohydrate antigen 125, play roles in predicting chemotherapy response and survival outcome in patients with ovarian clear cell carcinoma (OCCC).Methods: Preoperative leukocyte differential counts, as well as platelet, serum albumin, plasma D-dimer and CA-125 levels, were measured in patients with FIGO IC-IV ovarian clear cell cancer. The correlations of these hematological biomarkers with clinicopathological features, chemotherapy response, and survival outcomes were further analyzed. Survival time was estimated using the Kaplan-Meier model, whereas Cox regression was conducted for multivariate analysis.Results: Among the 84 patients, 28.6% were classified as platinum resistant, and 69.0% were platinum sensitive. Preoperative CA125, albumin, and D-dimer levels; neutrophil to lymphocyte ratios (NLR); and monocyte to lymphocyte ratios were significantly correlated with FIGO stage, residual tumor, and platinum response. Platelet to lymphocyte ratio was not related to platinum response (P=0.060). The median follow-up time was 28 months (range, 1 to 128 months). Preoperative CA125, albumin, and D-dimer levels were significant prognostic factors for overall survival (OS) and progression-free survival (PFS). In the univariate analysis, only NLR exhibited prognostic significance for PFS (P = 0.007). Multivariate analysis indicated that D-dimer > 3.27 (P = 0.001 for OS; P = 0.040 for PFS) and albumin <39.6 (P = 0.005 for OS and P = 0.041 for PFS) retained significance.Conclusions: Preoperative NLR has some predictive value for platinum resistance in patients with IC-IV stage OCCC but has little predictive effect on prognosis. Elevated D-dimer and reduced albumin might be potential biomarkers for worse response to first-line platinum-based chemotherapy and poor clinical outcomes.

scholarly journals Mismatch Repair Status as a Predictor of Benefit From Platinum-Based Adjuvant Therapy in Ovarian Clear Cell Carcinoma

2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 217s-217s
Author(s):  
J. Zhu ◽  
X. Wu ◽  
X. Ju
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Cell Carcinoma ◽  
Mismatch Repair ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Progression Free Survival ◽  
Ovarian Clear Cell Carcinoma ◽  
Free Survival ◽  
Pathologic Features

Background: Previous studies have indicated that patients with colorectal cancer who demonstrate defective DNA mismatch repair (dMMR) have clinical and pathologic features that distinguish them from patients who have proficient mismatch repair (pMMR) tumors. However, the influence of mismatch repair (MMR) status in ovarian clear cell carcinoma (OCCC) is still unknown. Aim: To evaluate the MMR statuses in OCCC and its correlation with clinicopathological and prognostic characteristics. Methods: MMR statuses were measured by tissue microarray–based immunohistochemistry from 120 OCCC patients. The associations of clinicopathologic features with progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier method and multivariate analysis was further performed by Cox regression model. Results: Overall, 120 OCCC patients met the entry criteria and their MMR status were detected, consisting of 24 patients with dMMR and 96 patients with pMMR. Tumors with dMMR were strongly associated with platinum-sensitive disease ( P = 0.008) and large tumor volume ( P = 0.028). Among all the patients who have received surgery, tumors with dMMR had a better progression-free survival and overall survival (OS) than those with pMMR (hazard ratio [HR] for recurrence, 0.459 [95% confidence interval (95% CI), 0.224-0.940]; P = 0.029; HR for death, 0.381 [95% CI, 0.170-0.853]; P = 0.015). In subgroup analysis, dMMR patients experienced a better PFS (HR, 0.242; P = 0.055) and OS (HR, 0.141; P = 0.039) than pMMR cases among early stages (I-II), but this difference was not observed in advanced stage (III-IV) patients. Meanwhile, pMMR was associated with more favorable prognosis than dMMR in platinum-resistant patients (PFS, HR: 0.317, P = 0.052; OS, HR: 0.370, P = 0.046). Multivariate analysis revealed that only advanced stages (III-IV) were adverse independent prognosticators for both PFS (HR, 5.938; [95% CI, 2.804-12.574], P < 0.001) and OS (HR, 6.209; [95% CI, 2.724-14.156], P < 0.001). Conclusion: MMR status in ovarian clear cell carcinoma is not only a prognostic indicator, but also appears to be a possible predictor for the use of platinum-based adjuvant chemotherapy.

scholarly journals DNA Mismatch Repair State And Clinical Pathological Characteristics Of Ovarian Clear Cell Carcinoma

2020 ◽  
Author(s):  
Qian Liu ◽  
Huimei Zhou ◽  
Jiaxin Yang ◽  
Xiaohua Shi
Keyword(s):  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Statistical Significance ◽  
Serous Carcinoma ◽  
Ovarian Clear Cell Carcinoma ◽  
Dna Mismatch ◽  
Prognosis Group ◽  
The Difference

Abstract Background: Ovarian clear cell carcinoma (OCCC) is a distinct subtype of epithelial ovarian cancer. With the exception of very early stage disease, OCCCs are associated with worse prognosis due to poor response to platinum-based chemotherapy compared with serous carcinoma. OCCCs with microsatellite instability (MSI) may represent a unique subset and may open an alternative therapeutic avenue for a fraction of patients with OCCC. The purpose of this study is to explore the role of DNA mismatch repair (MMR) in the genesis and development of clear cell carcinoma by determining the differential expression of MMR gene in different subtypes of ovarian carcinoma and the expression of MMR protein in clear cell carcinoma, so as to provide ideas for future tumor treatment.Results: The expression of MSH6 gene in HGSC group was higher than that in OCCC group, and the difference had statistical significance (P=0.01). The expression of MLH1 gene in OCCC group was higher than that in HGSC group, and the difference had statistical significance (P=0.0221). There was no significant difference in the expression of MSH2 gene between the two groups. There were no significant differences in the expression of the three genes between OCCC group with good prognosis (group G) and OCCC group with poor prognosis (group P). In order to further verify the expression of MMR protein in OCCC group, immunohistochemistry was performed, and the results showed that 92.3% of the patients (36/39) had pMMR, 7.69% of the patients (3/39) had dMMR. The average follow-up time of patients with dMMR was 19.3 months, and there was no recurrence or death.Conclusion: There were differences in the expression of MSH6 and MLH1 genes between ovarian clear cell carcinoma and high-grade serous carcinoma, indicating that the two subtypes of tumor may have different origins. The prognosis of clear cell carcinoma patients with dMMR was better as of the follow-up date, suggesting that dMMR may be an early event of clear cell carcinoma.

scholarly journals Role of endometriosis as a prognostic factor for post‑progression survival in ovarian clear cell carcinoma

2017 ◽  
Author(s):  
Hiroki Ishibashi ◽  
Masashi Takano ◽  
Morikazu Miyamoto ◽  
Hiroaki Soyama ◽  
Hiroko Matsuura ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Ovarian Clear Cell Carcinoma

Delayed Pancreatic Metastasis of Renal Clear Cell Carcinoma

2013 ◽  
Vol 13 (2) ◽  
pp. 79-80
Author(s):  
Zane Simtniece ◽  
Gatis Kirsakmens ◽  
Ilze Strumfa ◽  
Andrejs Vanags ◽  
Maris Pavars ◽  
...  
Keyword(s):  
Abdominal Pain ◽  
Surgical Treatment ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Primary Tumour ◽  
Renal Clear Cell Carcinoma ◽  
Pancreatic Metastasis ◽  
Distal Pancreatic Resection

Abstract Here, we report surgical treatment of a patient presenting with pancreatic metastasis (MTS) of renal clear cell carcinoma (RCC) 11 years after nephrectomy. RCC is one of few cancers that metastasise in pancreas. Jaundice, abdominal pain or gastrointestinal bleeding can develop; however, asymptomatic MTS can be discovered by follow-up after removal of the primary tumour. The patient, 67-year-old female was radiologically diagnosed with a clinically silent mass in the pancreatic body and underwent distal pancreatic resection. The postoperative period was smooth. Four months after the surgery, there were no signs of disease progression.

Sign in / Sign up

Export Citation Format

Share Document