p53 and erbB-2 Are Not Associated in Matched Cases of Primary and Metastatic Ovarian Carcinomas

Ovarian cancer has a high mortality rate largely due to the limited number of ovarian carcinomas detected at an early stage. Understanding the molecular changes occurring during the progression of ovarian carcinoma would aid in the development of therapies that may inhibit or target metastasis. Primary and metastatic lesions from 54 and 40 patients with advanced ovarian carcinoma, respectively (including matched primary and metastatic lesions from 30 patients) were evaluated for nuclear accumulation of p53 (clone BP53-12-1) and cytoplasmic and membranous immunostaining of p185 erbB-2 (clone 3B5) by immunohistochemistry. No differences in the immunostaining of p53 and p185erbB-2 (cytoplasm or membrane) were observed between primary and metastatic lesions of the matched cases. Similarly, no differences in the proportion of positive cases of p53 between primary and metastatic lesions of the matched cases was observed. Thus, novel therapies that target p53 or p185erbB-2 can utilize specimens from either primary or metastatic lesions to characterize these targets prior to therapy. Spearman correlations between p53 and p185erbB-2 (cytoplasm or membrane) immunohistochemistry scores were insignificant for the matched cases, all primary lesions, and all metastatic lesions. Also, no significant associations occurred between nuclear accumulation of p53 (positive versus negative) and phenotypic expression of p185erbB-2 (cytoplasm or membrane) immunostaining scores for the matched cases, all primary lesions, and all metastatic lesions. Thus, the nuclear accumulation of p53 and immunostaining of p185erbB-2 in the cytoplasm or on the cellular membranes are independent.

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MOLECULAR AND GENETIC SUBTYPES OF OVARIAN CANCER: PROSPECTS FOR FURTHER STUDIES

Problems in oncology ◽

10.37469/0507-3758-2019-65-1-56-62 ◽

2019 ◽

Vol 65 (1) ◽

pp. 56-62

Author(s):

Alisa Villert ◽

Larisa Kolomiets ◽

Natalya Yunusova ◽

Yevgeniya Fesik

Keyword(s):

Ovarian Cancer ◽

Ovarian Carcinoma ◽

Molecular Subtypes ◽

Survival Rates ◽

Consensus Algorithm ◽

Histopathological Diagnosis ◽

Low Grade ◽

High Grade ◽

Ovarian Carcinomas ◽

Genetic Subtypes

High-grade ovarian carcinoma is a histopathological diagnosis, however, at the molecular level, ovarian cancer represents a heterogeneous group of diseases. Studies aimed at identifying molecular genetic subtypes of ovarian cancer are conducted in order to find the answer to the question: can different molecular subgroups influence the choice of treatment? One of the achievements in this trend is the recognition of the dualistic model that categorizes various types of ovarian cancer into two groups designated high-grade (HG) and low-grade (LG) tumors. However, the tumor genome sequencing data suggest the existence of 6 ovarian carcinoma subtypes, including two LG and four HG subtypes. Subtype C1 exhibits a high stromal response and the lowest survival. Subtypes C2 and C4 demonstrate higher number of intratumoral CD3 + cells, lower stromal gene expression and better survival than sybtype C1. Subtype C5 (mesenchymal) is characterized by mesenchymal cells, over-expression of N-cadherin and P-cadherin, low expression of differentiation markers, and lower survival rates than C2 and C4. The use of a consensus algorithm to determine the subtype allows identification of only a minority of ovarian carcinomas (approximately 25%) therefore, the practical importance of this classification requires additional research. There is evidence that it makes sense to randomize tumors into groups with altered expression of angiogenic genes and groups with overexpression of the immune response genes, as in the angiogenic group there is a comparative superiority in terms of survival. The administration of bevacizumab in the angiogenic group improves survival, while the administration of bevacizumab in the immune group even worsens the outcome. Molecular subtypes with worse survival rates (proliferative and mesenchymal) also benefit most from bevacizumab treatment. This review focuses on some of the advances in understanding molecular, cellular, and genetic changes in ovarian carcinomas with the results achieved so far regarding the formulation of molecular subtypes of ovarian cancer, however further studies are needed.

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Emerging Role of Inhibin as a Biomarker for Ovarian Cancer

Women s Health ◽

10.1517/17455057.1.1.051 ◽

2005 ◽

Vol 1 (1) ◽

pp. 51-57 ◽

Cited By ~ 1

Author(s):

David M Robertson ◽

Martin K Oehler

Keyword(s):

Ovarian Cancer ◽

Granulosa Cell ◽

Early Stage ◽

Clinical Stage ◽

Survival Rates ◽

Ovarian Carcinomas ◽

Gynecological Malignancy ◽

Granulosa Cell Tumors ◽

Ovarian Cancers ◽

Specificity And Sensitivity

Ovarian cancer is the most lethal gynecological malignancy as it is diagnosed at a late clinical stage in more than 80% of patients. The development of diagnostic tests that can detect all types of ovarian cancers with high specificity and sensitivity, and at an early stage would improve survival rates. Serum inhibin is an ovarian hormone involved in the regulation of fertility, decreasing to undetectable levels after menopause. Certain ovarian malignancies, such as mucinous carcinomas and granulosa cell tumors, continue to produce inhibin, which is detectable in serum. A test for serum inhibin has been developed which is able to diagnose granulosa cell tumors and mucinous carcinomas with high accuracy. When the inhibin assay is used in conjunction with the CA125 test, which detects epithelial ovarian carcinomas, the two tests detect the majority of ovarian cancers with high sensitivity (95%) and specificity (95%). This article discusses the application of the inhibin test in ovarian cancer.

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Immunohistochemical validation of COL3A1, GPR158 and PITHD1 as prognostic biomarkers in early-stage ovarian carcinomas

BMC Cancer ◽

10.1186/s12885-019-6084-4 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 8

Author(s):

Hanna Engqvist ◽

Toshima Z. Parris ◽

Anikó Kovács ◽

Szilárd Nemes ◽

Elisabeth Werner Rönnerman ◽

...

Keyword(s):

Overall Survival ◽

Protein Expression ◽

Ovarian Carcinoma ◽

Early Stage ◽

Gynecological Cancer ◽

Expression Patterns ◽

Survival Rates ◽

Prognostic Biomarkers ◽

Ovarian Carcinomas ◽

Clear Cell Ovarian Carcinoma

Abstract Background Ovarian cancer is the main cause of gynecological cancer-associated death. However, 5-year survival rates differ dramatically between the five main ovarian carcinoma histotypes. Therefore, we need to have a better understanding of the mechanisms that promote histotype-specific ovarian carcinogenesis and identify novel prognostic biomarkers. Methods Here, we evaluated the prognostic role of 29 genes for early-stage (I and II) ovarian carcinomas (n = 206) using immunohistochemistry (IHC). Results We provide evidence of aberrant protein expression patterns for Collagen type III alpha 1 chain (COL3A1), G protein-coupled receptor 158 (GPR158) and PITH domain containing 1 (PITHD1). Kaplan-Meier survival analysis revealed that COL3A1 expression was associated with shorter overall survival in the four major histotypes of epithelial ovarian carcinoma patients (P value = 0.026, HR = 2.99 (95% CI 1.089–8.19)). Furthermore, GPR158 and PITHD1 were shown to be histotype-specific prognostic biomarkers, with elevated GPR158 expression patterns in mucinous ovarian carcinoma patients with unfavorable overall survival (P value = 0.00043, HR = 6.13 (95% CI 1.98–18.98)), and an association with lower PITHD1 protein expression and unfavorable overall and disease-specific survival in clear-cell ovarian carcinoma patients (P value = 0.012, HR = 0.22 (95% CI 0.058–0.80); P value = 0.003, HR = 0.17 (95% CI 0.043–0.64)). Conclusions The novel biomarkers identified here may improve prognostication at the time of diagnosis and may assist in the development of future individualized therapeutic strategies for ovarian carcinoma patients.

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Human Kallikrein 13 Protein in Ovarian Cancer Cytosols: A New Favorable Prognostic Marker

Journal of Clinical Oncology ◽

10.1200/jco.2004.05.144 ◽

2004 ◽

Vol 22 (4) ◽

pp. 678-685 ◽

Cited By ~ 50

Author(s):

Andreas Scorilas ◽

Carla A. Borgoño ◽

Nadia Harbeck ◽

Julia Dorn ◽

Barbara Schmalfeldt ◽

...

Keyword(s):

Ovarian Cancer ◽

Ovarian Tumor ◽

Cox Regression ◽

Early Stage ◽

Mrna Level ◽

Enzyme Linked Immunosorbent Assay ◽

Hormone Regulation ◽

Ovarian Carcinomas ◽

Favorable Prognosis ◽

Potential Biomarker

PurposeHuman kallikrein 13 (hK13; encoded by the KLK13 gene) is a secreted serine protease expressed in endocrine tissues, including the prostate, testis, breast, and ovary. We have previously reported steroid hormone regulation of the KLK13 gene and its clinical value as a marker of favorable prognosis in breast cancer at the mRNA level. We hypothesized that hK13 may represent a potential biomarker for ovarian carcinomas.Patients and MethodsUsing a newly developed enzyme-linked immunosorbent assay (ELISA), hK13 levels were quantified in 131 ovarian tumor extracts and correlated with various clinicopathological variables and outcome (progression-free survival [PFS], overall survival [OS]), over a median follow-up period of 42 months.ResultshK13 concentration in ovarian tumor cytosols ranged from 0 to 18.4 ng/mg of total protein. An optimal cutoff value of 0.13 ng/mg (67thpercentile) was selected, based on the ability of hK13 values to predict the PFS of the study population, to categorize tumors as hK13-positive or negative. Women with hK13-positive tumors most often had early stage (stage I/II) disease, no residual tumor after surgery and optimal debulking success (P < .05). Univariate and multivariate Cox regression analyses revealed that patients with hK13-positive tumors had a significantly longer PFS and OS than hK13-negative patients (P < .05). Kaplan-Meier survival curves further confirmed a reduced risk of relapse and death in women with hK13-positive tumors (P = .007 and P = .002, respectively).ConclusionThese results indicate that hK13 is an independent marker of favorable prognosis in ovarian cancer.

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A randomized multicenter phase II study on neoadjuvant chemotherapy with carboplatin and docetaxel in advanced ovarian carcinomas (PRIMOVAR)

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.15025 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 15025-15025 ◽

Cited By ~ 2

Author(s):

T. Park-Simon ◽

F. Jänicke ◽

O. Ortmann ◽

J. Hilfrich ◽

G. Breitbach ◽

...

Keyword(s):

Ovarian Cancer ◽

Neoadjuvant Chemotherapy ◽

Ovarian Carcinoma ◽

Preoperative Chemotherapy ◽

Response Rate ◽

Tumor Resection ◽

Residual Tumor ◽

Ovarian Carcinomas ◽

Number Of Patients ◽

Postoperative Residual

15025 Background: In the past years the concept of neoadjuvant chemotherapy and interval laparotomy has emerged for patients with advanced ovarian cancer and unfavorable prognosis (e.g. diffuse peritoneal carcinosis). In a recent study on neoadjuvant chemotherapy higher tumor resection rates and longer median survival were demonstrated in patients with advanced ovarian carcinoma and ascites >500ml. Most studies use three cycles of preoperative chemotherapy. However, chemoresistant tumorclones may be induced by increasing number of preoperative chemotherapy cycles. The purpose of this study is to evaluate the optimal number of cycles prior to interval laparotomy. Methods: 67/73 patients with advanced serous ovarian carcinoma (FIGO IIIc n = 48, FIGO IV n = 19) and ascites >500ml were randomized into two arms, receiving either 2 (n = 33) or 3 (n = 34) cycles of Carboplatin (AUC5) and Docetaxel (75mg/m2) before interval laparotomy. Postoperatively, they received either 4 or 3 additional cycles. Response rate and postoperative residual tumor were evaluated. Results: Surgical response was assessed during interval laparotomy. At present 32 patients underwent tumordebulking. Partial remission was observed in 28/32 patients irrespective of the number of preoperative chemotherapy cycles. Two patients in each arm showed stable disease. Optimal cytoreduction was achieved in 25/32 patients. No severe adverse events were reported. Six of 73 patients were not eligible. Two patients were excluded due to therapy-unrelated events. In 4 patients ovarian cancer was excluded by laparoscopy prior to neoadjuvant chemotherapy. Conclusions: Neoadjuvant chemotherapy followed by interval laparotomy was safe and well tolerated. Diagnostic laparoscopy prior to neoadjuvant chemotherapy allowed differentiation of primary ovarian cancers from tumors of other origin. In these cases laparotomy could be circumvented. Optimal tumor reduction was achieved in a significant number of patients. Response rate and postoperative residual tumor were essentially the same in both arms. Our data indicate that two cycles of preoperative chemotherapy may be the preferential choice of therapy for future studies. No significant financial relationships to disclose.

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Tumor stroma proportion to predict platinum chemoresistance in primary ovarian carcinomas: A prospective study.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.5581 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 5581-5581

Author(s):

Emil Lou ◽

Rachel Isaksson Vogel ◽

Spencer Hoostal ◽

Aaron Grad ◽

Minnu Monu ◽

...

Keyword(s):

Ovarian Cancer ◽

Ovarian Carcinoma ◽

Cancer Patients ◽

Clinical Decision Making ◽

Prospective Trial ◽

Predictive Biomarkers ◽

Tumor Stroma ◽

Ca 125 ◽

Ovarian Carcinomas ◽

Major Barrier

5581 Background: Platinum chemotherapy resistance occurs in approximately 25% of patients with ovarian carcinoma and represents a major barrier to effective care of this patient population. To date there are no effective nor validate predictive biomarkers of chemoresistance of ovarian carcinomas. We performed a prospective trial designed to enroll patients with ovarian masses suspicious for ovarian cancer, with the goal of identifying tumor-based predictive biomarkers of platinum resistance. Methods: 60 women were enrolled on the study. Tumor specimens were collected from 49 of these women with newly diagnosed pelvic masses, of which 29 were found to have histopathologically proven primary ovarian carcinoma. Of these primary malignant cases, 24 had specimens accessible for assessment of tumor-stroma proportion and data available regarding chemosensitive vs chemoresistance status via review of the medical record using a UMN IRB-approved protocol. Tumor slices were stained with H&E and also for antibodies against two microRNAs (29b and 199a) differentially expressed in ovarian cancer cell lines. Tumor-stroma proportions were assessed by two experienced pathologists blinded to chemoresistance status, with <50% stroma scored as low proportion, >50% scored as high proportion. Results: The average age of assessed patients with malignant tumors was 62. 87.5% had high-grade epithelial carcinomas. Baseline median CA-125 was 416 (range 32-2782). 80% of ovarian cancer patients with chemoresistance had tumor stroma proportions >50%; 73.7% of cancer patients with chemosensitive tumors had proportions <50% (p-value: 0.047). Expression of miR29b or 199a did not significantly correlate with chemoresistance. Conclusions: Tumor-stroma proportion is a useful predictive biomarker of platinum chemoresistance. If validated in larger datasets, it would be a relatively inexpensive and helpful tool for tailoring treatment strategies and clinical decision-making in women with ovarian cancer.

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Gender-Specific Association Of Oxidative Stress And Immune Response In Septic Shock Mortality using NMR based metabolomics

Molecular Omics ◽

10.1039/d1mo00398d ◽

2021 ◽

Author(s):

Swarnima Pandey ◽

Mohd Adnan Siddiqui ◽

Surendra Kumar Trigun ◽

Afzal Azim ◽

Neeraj Sinha

Keyword(s):

Oxidative Stress ◽

Septic Shock ◽

Immune Response ◽

Mortality Rate ◽

High Mortality ◽

Early Stage ◽

Treatment Protocol ◽

Specific Association ◽

Sepsis And Septic Shock ◽

Gender Specific

Background: Sepsis and septic shock are still associated with a high mortality rate. Early-stage prediction of septic shock outcomes would be helpful to clinicians for designing their treatment protocol. In...

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A Study of CD44 Positive Cancer Cells in Epithelial Ovarian Cancer and their Correlation with P53 And Ki67

Journal of Laboratory Physicians ◽

10.1055/s-0041-1724235 ◽

2021 ◽

Author(s):

Ketaki Kar ◽

Suman Ghosh ◽

Anup Kumar Roy

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Cancer Cells ◽

Early Stage ◽

Prognostic Significance ◽

P Value ◽

Borderline Tumor ◽

Ovarian Carcinomas ◽

Specific Symptom ◽

Cd44 Expression

Abstract Context Epithelial ovarian carcinomas are one of the most common lethal gynecological malignancies. There is no specific symptom or biomarker for detection of this malignancy in early stage. So, the advanced stage, nature of frequent recurrences, and resistance to chemotherapies make it very difficult to deliver proper treatment to patients. Efforts are on to identify the presence of cancer stem cell by using a specific biomarker in epithelial ovarian cancer in the early stage. Objectives This study aims to identify the CD44 positive cancer cells in epithelial ovarian carcinoma of different histopathological types. It also intends to correlate the expression of CD44 with the expression of p53 and Ki67. Materials and Methods Sections from diagnosed specimens of ovarian epithelial neoplasm had been fixed in 10% formalin and embedded in paraffin, and they were used for immunohistochemical (IHC) staining for CD44, p53, and Ki67, using a peroxidase kit with mouse monoclonal antibodies. Then, the slides were evaluated for both tumor cell percentage and intensity of immunoreactivity. Statistical Analysis Chi-square had been used to find the significance of study. Significance level was considered at p value < 0.05 Results In this study, 40 patients were included in a period of one and a half years. The present study suggested that the levels of CD44 expression were increased in epithelial ovarian cancer compared to borderline tumor. CD44 was positively correlated with the ki67 expression and tumor grade. High-grade serous, mucinous, and endometrioid tumors were associated with high CD44 expression. Positivity of CD44 was found significantly higher in case of positive status of p53 (z = 3.65; p < 0.0001). Conclusion We can correlate CD44 positive cancer stem cells with grade of ovarian carcinomas, but for prognostic significance and therapeutic applications, more corroborative and multicentric works in this field are needed. CD44 can be targeted for therapy in recurrent and resistant cases of ovarian cancer.

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MicroRNA-497-5p Functions as a Modulator of Apoptosis by Regulating Metadherin in Ovarian Cancer

Cell Transplantation ◽

10.1177/0963689719897061 ◽

2020 ◽

Vol 29 ◽

pp. 096368971989706 ◽

Cited By ~ 1

Author(s):

Chunyan Liu ◽

Anne Bordeaux ◽

Stanka Hettich ◽

Suhui Han

Keyword(s):

Ovarian Cancer ◽

Mortality Rate ◽

Molecular Mechanism ◽

High Mortality ◽

Cell Apoptosis ◽

Untranslated Region ◽

Protein Levels ◽

Enhanced Expression ◽

Related Proteins

Ovarian cancer (OC) has a high mortality rate among women worldwide. However, even with the advances in detection and therapeutics, the number of cases is increasing worldwide. Increasingly, microRNAs (miRNAs), including miR-497-5p, have been implicated in the progression of many cancers, but the role of miR-497-5p in OC remains unknown. The purpose of this study was to investigate the underlying molecular mechanism of miR-497-5p in OC. Herein, we find that miR-497-5p is down-regulated in OC tissues, and overexpression of miR-497-5p enhances apoptosis in OC cells. The increased apoptosis was correlated with enhanced expression of apoptosis-related proteins. MiR-497-5p directly bound the 3’-untranslated region of metadherin (MTDH), leading to the reduction of MTDH in mRNA and protein levels. Moreover, MTDH knockout promoted the apoptosis of OC cells. Taken together, we conclude that miR-497-5p contributes to cell apoptosis in OC by regulating MTDH.

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Histologic Subtypes of Ovarian Carcinoma: Selected Diagnostic and Classification Problems in Bulgaria: Is Low Hospital Volume an Issue?

Tumori Journal ◽

10.5301/tj.5000571 ◽

2016 ◽

Vol 103 (2) ◽

pp. 148-154 ◽

Cited By ~ 2

Author(s):

Vesela Ivanova ◽

Tihomir Dikov ◽

Nadya Dimitrova

Keyword(s):

Ovarian Cancer ◽

Quality Of Care ◽

Ovarian Carcinoma ◽

Cancer Patients ◽

Hospital Volume ◽

Clear Cell ◽

High Volume ◽

Ovarian Carcinomas ◽

Low Volume

Purpose To provide an overview of the morphologic subtypes of ovarian carcinomas in Bulgaria in relation to current healthcare organization using Bulgarian National Cancer Registry data. Further, we investigated hospital volume as a factor influencing the quality of care for patients with ovarian cancer. Methods Bulgarian National Cancer Registry ovarian carcinoma data were retrieved (2009-2011) and distribution of histologic types was analyzed. Cases were divided and compared with respect to main treatment: no surgery, surgery at hospitals dealing with ≥30 ovarian cancer patients/year (high volume), and surgery at hospitals dealing with <30 ovarian cancer patients/year (low volume). We then estimated the odds of being diagnosed with adenocarcinoma and carcinoma not otherwise specified (NOS) vs specified morphologies (serous, endometrioid, clear cell, and mucinous), including age, grade, stage, and hospital volume, in a logistic regression model. Results A total of 2,041 ovarian carcinomas were distributed as follows: serous 47.7%, mucinous 11.9%, endometrioid 5.8%, clear cell 1.8%, and adenocarcinoma and carcinoma NOS 32.5%. More than half of cancer patients (n = 1,100, 53.9%) were surgically treated in low-volume hospitals and they had a larger proportion of cases with adenocarcinoma and carcinoma NOS: 33.3%, in comparison with 24.0% in high-volume hospitals (p<0.0001). The odds of being diagnosed with unspecified morphology, assumed as a proxy of suboptimal quality of care, are higher for patients surgically treated in low-volume hospitals (odds ratio 1.50 [95% confidence interval 1.21-1.87]) compared with high-volume hospitals after adjustment for age, stage, and grade. Conclusions The results of our study may serve policymakers and healthcare professionals when optimizing diagnosis and treatment of ovarian cancer in Bulgaria.

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