scholarly journals Immunohistochemical Biomarkers as a Surrogate of Molecular Analysis in Ovarian Carcinomas: A Review of the Literature

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 199 ◽  
Author(s):  
Giacomo Santandrea ◽  
Simonetta Piana ◽  
Riccardo Valli ◽  
Magda Zanelli ◽  
Elisa Gasparini ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Molecular Analysis ◽  
Immunohistochemical Analysis ◽  
Cost Effective ◽  
Mucinous Carcinoma ◽  
Serous Carcinoma ◽  
Malignant Neoplasms ◽  
Low Grade ◽  
Ovarian Carcinomas ◽  
Novel Target

The term “ovarian carcinoma” encompasses at least five different malignant neoplasms: high-grade serous carcinoma, low-grade serous carcinoma, endometrioid carcinoma, mucinous carcinoma, and clear cell carcinoma. These five histotypes demonstrated distinctive histological, molecular, and clinical features. The rise of novel target therapies and of a tailored oncological approach has demanded an integrated multidisciplinary approach in the setting of ovarian carcinoma. The need to implement a molecular-based classification in the worldwide diagnostic and therapeutic setting of ovarian cancer demanded a search for easy-to-use and cost-effective molecular-surrogate biomarkers, relying particularly on immunohistochemical analysis. The present review focuses on the role of immunohistochemistry as a surrogate of molecular analysis in the everyday diagnostic approach to ovarian carcinomas.

scholarly journals The Evolution of Ovarian Carcinoma Subclassification

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 416
Author(s):  
Martin Köbel ◽  
Eun Young Kang
Keyword(s):  
Ovarian Carcinoma ◽  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Expression Profiles ◽  
Model Systems ◽  
Serous Carcinoma ◽  
Molecular Profile ◽  
Low Grade ◽  
Ovarian Carcinomas ◽  
Immunohistochemical Markers

The phenotypically informed histotype classification remains the mainstay of ovarian carcinoma subclassification. Histotypes of ovarian epithelial neoplasms have evolved with each edition of the WHO Classification of Female Genital Tumours. The current fifth edition (2020) lists five principal histotypes: high-grade serous carcinoma (HGSC), low-grade serous carcinoma (LGSC), mucinous carcinoma (MC), endometrioid carcinoma (EC) and clear cell carcinoma (CCC). Since histotypes arise from different cells of origin, cell lineage-specific diagnostic immunohistochemical markers and histotype-specific oncogenic alterations can confirm the morphological diagnosis. A four-marker immunohistochemical panel (WT1/p53/napsin A/PR) can distinguish the five principal histotypes with high accuracy, and additional immunohistochemical markers can be used depending on the diagnostic considerations. Histotypes are further stratified into molecular subtypes and assessed with predictive biomarker tests. HGSCs have recently been subclassified based on mechanisms of chromosomal instability, mRNA expression profiles or individual candidate biomarkers. ECs are composed of the same molecular subtypes (POLE-mutated/mismatch repair-deficient/no specific molecular profile/p53-abnormal) with the same prognostic stratification as their endometrial counterparts. Although methylation analyses and gene expression and sequencing showed at least two clusters, the molecular subtypes of CCCs remain largely elusive to date. Mutational and immunohistochemical data on LGSC have suggested five molecular subtypes with prognostic differences. While our understanding of the molecular composition of ovarian carcinomas has significantly advanced and continues to evolve, the need for treatment options suitable for these alterations is becoming more obvious. Further preclinical studies using histotype-defined and molecular subtype-characterized model systems are needed to expand the therapeutic spectrum for women diagnosed with ovarian carcinomas.

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

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.

scholarly journals Gynecologic Serous Carcinoma: An Immunohistochemical Analysis of Malignant Body Fluid Specimens

2018 ◽  
Vol 143 (6) ◽  
pp. 677-682
Author(s):  
Shuyue Ren ◽  
William Klump
Keyword(s):  
Body Fluid ◽  
Germ Cell Tumors ◽  
Immunohistochemical Analysis ◽  
Serous Carcinoma ◽  
Low Grade ◽  
High Grade ◽  
Gynecologic Malignancy ◽  
Immunohistochemical Markers ◽  
Immunohistochemical Studies ◽  
Positive Results

Context.— Evaluation of fluid specimens involved by serous carcinoma might potentially include PAX8, GATA3, Uroplakin II, SOX2, and SALL4 antibodies. Those markers are commonly employed for diagnosing carcinomas of various types, including urothelial malignancies and germ cell tumors. There have been no comprehensive immunohistochemical studies, to our knowledge, for those markers on fluid specimens involved by serous carcinoma. Objective.— To evaluate immunohistochemical markers PAX8, GATA3, SOX2, uroplakin II, and SALL4 in the diagnosis of high-grade serous carcinoma in fluid specimens. Design.— We examined 113 fluids (96 ascites specimens and 17 pleural fluid specimens) that were positive for carcinoma. Most (94 cases; 83.2%) consisted of high-grade serous carcinoma of Müllerian origin. Nineteen cases of non–high-grade serous carcinoma (including one case of low-grade serous carcinoma) of gynecologic origin were also included as anecdotal data. Results.— In 113 fluid specimens with positive results for carcinoma, including nonserous types, 99 (87.6%) had positive results for PAX8, 19 (16.8%) for GATA3; 19 (16.8%) for SOX2, 23 (20.4%) for uroplakin II, and 8 (7.1%) for SALL4. Of 94 fluids (83.2%) involved with high-grade serous carcinoma, 84 (89.4%) had positive results for PAX8, 18 (19.1%) for GATA3, 17 (18.1%) for SOX2, 22 (23.4%) for uroplakin II, and 8 (8.5%) for SALL4. Some of these specimens showed reactivity for more than one immunohistochemical marker. Conclusions.— Most fluids involving high-grade serous carcinoma showed positive results for PAX8, and some cases expressed GATA3, SOX2, uroplakin II, and SALL4. Serous carcinoma in fluids may be positive for immunohistochemical markers not thought of traditionally as associated with gynecologic malignancy, an important consideration in avoiding misdiagnosis.

scholarly journals Ultrasound, macroscopic and histological features of serous epithelial ovarian carcinomas

2020 ◽  
pp. ijgc-2020-001473
Author(s):  
Paola Romeo ◽  
Damiano Arciuolo ◽  
Maria Cristina Moruzzi ◽  
Francesca Moro
Keyword(s):  
Ovarian Carcinoma ◽  
Low Grade ◽  
High Grade ◽  
Ovarian Carcinomas ◽  
Histological Features ◽  
Serous Ovarian Carcinoma ◽  
Epithelial Ovarian Carcinomas

We present a video showing two cases of serous epithelial ovarian carcinomas. The first video shows clinical, ultrasound, macroscopic, and histological features of a patient with high grade serous ovarian carcinoma. The second video presents clinical, ultrasound, macroscopic, and histological features of a patient with low grade serous ovarian carcinoma.

Cancer Stem Cell and Embryonic Development-Associated Molecules Contribute to Prognostic Significance in Ovarian Cancer

2012 ◽  
Vol 22 (1) ◽  
pp. 23-29 ◽  
Author(s):  
Gulperi Oktem ◽  
Muzaffer Sanci ◽  
Ayhan Bilir ◽  
Yusuf Yildirim ◽  
Sibel D. Kececi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cancer Stem Cell ◽  
Histological Grade ◽  
Prognostic Significance ◽  
Notch Pathway ◽  
Mucinous Carcinoma ◽  
Clinicopathological Characteristics ◽  
Serous Carcinoma ◽  
Ovarian Carcinomas ◽  
Clinical Prognosis

ObjectivesEmbryonic molecules and cancer stem cell signaling resemble each other, and they organize cancer modality. We hypothesized that similar immunohistochemical expressions between tumor spheroids and patients’ samples compared with clinical relevance would give an important clue in patients’ prognosis.MethodsImmunohistochemical expression of c-kit, Notch1, Jagged1, and Delta1 in 50 cases of primary ovarian tumors (10 endometrioid, 10 serous, 10 mucinous adenocarcinoma, 10 borderline serous, and 10 borderline mucinous tumors) and MDAH-2774 spheroids were investigated. Results were compared in both spheroids and tumor samples with morphologic parameters (histological grade) and clinical data (age, stage, tumor size, and metastasis).ResultsHigh c-kit and Notch1 immunoreactivity was shown in spheroids, but interestingly immunoreactivity of these molecules in tumor samples was different from patients’ clinicopathological characteristics. In serous carcinoma, metastasis correlated with Notch1 immunoexpression; in mucinous carcinoma, Jagged1 immunohistochemistry correlated with grade, stage, and metastasis of tumor; in borderline serous and mucinous tumors, Jagged1 correlated with high grade. Moreover, Jagged1 correlated with stage and Notch1 with size in borderline mucinous tumor. Endometrioid carcinoma statistics showed that there was a correlation between age and Notch1 expression.ConclusionNotch1, Jagged1, and Delta1 expressions might be useful markers for clinical prognosis of ovarian carcinomas; and Notch pathway, one of the most intensively studied putative therapeutic targets, may be a useful marker for cancer. Consequently, Jagged1 could be a marker for tumor grades and Notch1 as a marker for metastases.

scholarly journals Clinicopathological Spectrum of Surface Epithelial Ovarian Carcinoma and its Association with Serum CA-125 Levels: A Cohort Study

2021 ◽  
Author(s):  
Nisha Singla ◽  
Sarita Nibhoria ◽  
Kanwardeep Kaur Tiwana ◽  
Prince Gupta
Keyword(s):  
Cohort Study ◽  
Ovarian Carcinoma ◽  
World Health ◽  
Serous Carcinoma ◽  
Ca 125 ◽  
Categorical Variables ◽  
Low Grade ◽  
High Grade ◽  
History Of ◽  
Epithelial Tumours

Introduction: The ovaries are the primary female reproductive organs and endocrine glands. Ovarian carcinoma has often been called as the silent killer because the symptoms may develop so late that the chances of cure are very poor. According to World Health Organisation (WHO) ovarian tumours are classified based upon their most probable tissue of origin: surface epithelial (65%), germ cell (15%), sex cord-stromal (10%), metastases (5%) and miscellaneous. The malignant surface epithelial tumours are further classified by cell type into serous, mucinous, endometrioid, clear cell, brenner, seromucinous and undifferentiated carcinoma. The most widely used tumour marker in ovarian carcinoma is CA-125 which is considered as gold standard. Aim : To find the utility of serum CA-125 levels in histopathological variants of malignant surface epithelial tumours, degree of differentiation and their distribution according to clinical data pertaining to age, parity, history of use of oral contraceptive pills/ovulation inducing drugs and family history of carcinoma ovary/breast or colon. Materials and Methods: A prospective study (cohort study) was done at Guru Gobind Singh Medical College and Hospital, Faridkot over a period of 1.5 year (April 2017-oct 2018) on 50 ovarian masses which were diagnosed as ovarian carcinoma. Data was represented as frequencies and percentages for categorical variables and as means and standard deviations for continuous variables. Analysis was done using Statistical Package for Social Sciences (SPSS) v 20.0.0. Results: Serous carcinoma (80%) topped among all the histological variants. Serous high grade carcinoma was more common than serous low grade carcinoma. Maximum rise of serum CA-125 levels were seen in serous carcinoma. Among serous carcinomas, mean serum CA-125 levels were more in high grade serous carcinoma than low grade serous carcinoma and the results were statistically significant. conclusion: Serum CA-125 level is a great tool for diagnosis, follow-up and prognosis of ovarian carcinomas.

Low grade serous ovarian carcinoma: identifying variations in practice patterns

2019 ◽  
Vol 29 (1) ◽  
pp. 174-180 ◽  
Author(s):  
John Siemon ◽  
David M Gershenson ◽  
Brian Slomovitz ◽  
Matthew Schlumbrecht
Keyword(s):  
Ovarian Carcinoma ◽  
Practice Patterns ◽  
Gynecologic Oncology ◽  
Braf Inhibitor ◽  
Primary Treatment ◽  
Treatment Modalities ◽  
Serous Carcinoma ◽  
Low Grade ◽  
Serous Ovarian Carcinoma ◽  
Platinum Resistant

ObjectivesLow grade serous ovarian carcinoma is a rare subtype of ovarian cancer with an indolent and chemorefractory course. As such, treatment strategies among practitioners are not uniformly known. The primary objective of this study was to identify differences in practice patterns among physicians who treat low grade serous carcinoma.Methods MaterialsA de novo survey was distributed to members of the Society of Gynecologic Oncology. Questions about demographics, management of primary and recurrent disease, and use of consolidation therapy were included. Statistical analyses were performed using χ2 and Fisher’s exact tests.Results194 gynecologic oncologists completed the survey. Approximately two-thirds of respondents practiced in a university based setting and treated a high volume of ovarian cancers, including low grade serous carcinoma. 82% recommended somatic testing during treatment and 84% routinely sent patients for genetic counseling. Treatment preferences for primary disease varied by debulking status. 48% of practitioners used hormone antagonism as consolidation after primary treatment. Secondary cytoreduction was preferred for patients with platinum sensitive recurrence and a long disease free interval following primary treatment (P<0.001). Hormone antagonism was the preferred treatment for the first platinum resistant recurrence (54%), while a BRAF inhibitor was the preferred agent in platinum resistant recurrence in the presence of a known BRAF mutation (56%).ConclusionsThere was significant variation in the preferred management of low grade serous carcinoma among practitioners. Further efforts to improve knowledge of this disease, identify optimal treatment modalities, and provide guidelines for management should be encouraged.

scholarly journals Effect of prophylactic salpingectomy on ovarian function in premenopausal women in tertiary referral center

2017 ◽  
Vol 6 (10) ◽  
pp. 4243
Author(s):  
Tamer M. Abdel Dayem ◽  
Amira M. Badawy
Keyword(s):  
Ovarian Function ◽  
Premenopausal Women ◽  
Serous Carcinoma ◽  
Low Grade ◽  
Type I ◽  
Ovarian Cancer Risk ◽  
High Grade ◽  
Ovarian Carcinomas ◽  
Ovarian Cancers ◽  
Prophylactic Salpingectomy

Background: Epithelial ovarian cancers (EOCs) are the most common cause of death from gynaecological malignancy. Serous ovarian carcinomas represent (68%) of Epithelial ovarian cancers, they are further divided into low-grade (type I) and high-grade (type II) serous ovarian carcinomas. There has been increasing evidence that fallopian tubes are considered the most important site of origin of pelvic high grade serous carcinoma. Salpingectomy is thought to be effective in reducing ovarian cancer risk in the future and prolonging average life expectancy, however, there are some concerns regarding ovarian function after elective salpingectomy in premenopausal women. The current study was carried out to assess the effect of salpingectomy on ovarian function in premenopausal women.Methods: 60 premenopausal cases were recruited and subjected to open abdominal hysterectomy without oophorectomy (for benign indications). Included cases were below 45 years, with documented active ovarian functions. Cases with genital malignancy, ovarian gross pathology and suspected or known ovarian failure were excluded. Cases were randomly allocated to one of two groups; group-A (where salpingectomy was performed), and group-B (where salpingectomy was not done). For all patients, ovarian functions were assessed prior operation, and at one and three months after operation using serum anti-Mullarian hormone (AMH) as well as early follicular antral follicular count (AFC), serum follicle stimulating hormone (FSH) and serum oestradiol (E2).Results: The mean pre-operative AFC, AMH, FSH, and E2 levels showed no significant changes after operation at one and three months postoperative follow up in both studied groups, denoting preserved ovarian function in both groups.Conclusions: Prophylactic salpingectomy is a safe and simple procedure that has no effect on ovarian reserve or function when performed in premenopausal women.

Increased cyclooxygenase-2 (COX-2) and P-glycoprotein-170 (MDR1) expression is associated with chemotherapy resistance and poor prognosis. Analysis in ovarian carcinoma patients with low and high survival

2005 ◽  
Vol 15 (2) ◽  
pp. 255-260 ◽  
Author(s):  
M. R. Raspollini ◽  
G. Amunni ◽  
A. Villanucci ◽  
V. Boddi ◽  
G. L. Taddei
Keyword(s):  
Surgical Treatment ◽  
Ovarian Carcinoma ◽  
Cyclooxygenase 2 ◽  
Serous Carcinoma ◽  
High Survival ◽  
Ovarian Carcinomas ◽  
P Glycoprotein ◽  
Response To Chemotherapy ◽  
Progression Of Disease ◽  
Cox 2

The aim of the study is to test the prognostic value of cyclooxygenase-2 (COX-2) and P-glycoprotein in relation to responsiveness to chemotherapy in ovarian carcinoma patients with “shorter and longer” survival. We evaluated 52 ovarian carcinomas homogeneous for stage, histologic type, grade of differentiation, and surgical and chemotherapeutic treatment. Twenty-eight of the patients had died of progression of disease no later than 2 years after primary surgical treatment, while 24 patients were alive with no evident disease 5 years after primary surgical treatment. In logistic regression analysis, COX-2 and P-glycoprotein, when analyzed one by one, are significant (P = 0.017 and P < 0.0005, respectively). P-glycoprotein is correlated with COX-2 (P = 0.008, Fisher's exact test); moreover, both COX-2 and the P-glycoprotein are correlated with clinical response to chemotherapy (P = 0.022 and P < 0.0005, respectively, Chi-square test). Our data suggest that COX-2 and P-glycoprotein may have prognostic significance in advanced ovarian serous carcinoma. The COX-2 and the P-glycoprotein overexpressions are correlated to one another and both with a progression of disease during the first-line chemotherapy. The administration of a COX-2 inhibitor in association with chemotherapy in ovarian carcinoma patients may improve the tumor chemosensibility and the overall survival.

scholarly journals Molecular analysis of a rare case of low-grade primary peritoneal serous carcinoma in a male

Rare Tumors ◽  
2020 ◽  
Vol 12 ◽  
pp. 203636132097921
Author(s):  
Vladislav V Makarenko ◽  
Dina Kandil ◽  
Ediz F Cosar ◽  
Lloyd Hutchinson ◽  
Ashraf Khan
Keyword(s):  
Gene Mutation ◽  
Molecular Analysis ◽  
Male Patient ◽  
Rare Case ◽  
Serous Carcinoma ◽  
Low Grade ◽  
Male Patients

Primary peritoneal serous carcinomas (PPSC) are exceedingly rare in male patients. Only a few cases were reported, and mostly with the limited immunophenotypical characterization. No molecular analysis of PPSC in males has been previously performed. We here describe another case of PPSC in a male patient. A comprehensive molecular analysis of the tumor revealed SF3B1 gene mutation as a possible driver.

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