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 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.

Assessment of TP53 mutation using purified tissue samples of ovarian serous carcinomas reveals a higher mutation rate than previously reported and does not correlate with drug resistance

2008 ◽  
Vol 18 (3) ◽  
pp. 487-491 ◽  
Author(s):  
R. SALANI ◽  
R. J. KURMAN ◽  
R. GIUNTOLI ◽  
G. GARDNER ◽  
R. BRISTOW ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mutation Frequency ◽  
Clinical Stage ◽  
Serous Carcinoma ◽  
Low Grade ◽  
High Grade ◽  
Mutation Status ◽  
Tumor Dna ◽  
Serous Tumors

The TP53 mutation frequency in ovarian serous carcinomas has been reported to range between 50% and 80%, but a stringent analysis of TP53 using purified epithelial samples has not yet been performed to accurately assess the mutation frequency and to correlate it with the histologic grade. The purpose of this study was to assess the TP53 mutational profile in a relatively large series of high-grade (53 primary and 18 recurrent) and 13 low-grade ovarian serous tumors using DNA isolated from affinity-purified tumor cells and to correlate it with in vitro drug resistance. All samples were affinity purified, and the tumor DNA was analyzed for TP53 mutations in exons 4–9. In vitro drug resistance assays to carboplatin, cisplatin, paclitaxel, and taxotere were performed on the same tumor samples and correlated with the TP53 mutation status. TP53 mutations were detected in 57 (80.3%) of 71 high-grade carcinomas and in one (7.8%) of 13 low-grade serous tumors (an invasive low-grade serous carcinoma). The mutations were predominantly missense mutations (59.6%). TP53 mutations were associated with high-grade serous carcinomas and recurrent disease (P < 0.0001). There was no statistically significant correlation between TP53 mutation status and drug resistance assays or clinical stage (P > 0.25). The frequency of TP53 mutations using purified tumor DNA from ovarian serous carcinomas was 80.3%, which is much higher than previously reported. Furthermore, we found that TP53 is not directly involved in the development of drug resistance in high-grade ovarian serous carcinomas.

Should All Cases of High-Grade Serous Ovarian, Tubal, and Primary Peritoneal Carcinomas Be Reclassified as Tubo-Ovarian Serous Carcinoma?

2015 ◽  
Vol 25 (7) ◽  
pp. 1201-1207 ◽  
Author(s):  
Esther Louise Moss ◽  
Tim Evans ◽  
Philippa Pearmain ◽  
Sarah Askew ◽  
Kavita Singh ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clear Cell ◽  
Stage Iii ◽  
Serous Carcinoma ◽  
Low Grade ◽  
Type I ◽  
High Grade ◽  
Type Ii ◽  
Ovarian Serous Carcinoma ◽  
Significant Difference

IntroductionThe dualistic theory of ovarian carcinogenesis proposes that epithelial “ovarian” cancer is not one entity with several histological subtypes but a collection of different diseases arising from cells of different origin, some of which may not originate in the ovarian surface epithelium.MethodsAll cases referred to the Pan-Birmingham Gynaecological Cancer Centre with an ovarian, tubal, or primary peritoneal cancer between April 2006 and April 2012 were identified from the West Midlands Cancer Registry. Tumors were classified into type I (low-grade endometrioid, clear cell, mucinous, and low-grade serous) and type II (high-grade serous, high-grade endometrioid, carcinosarcoma, and undifferentiated) cancers.ResultsOvarian (83.5%), tubal (4.3%), or primary peritoneal carcinoma (12.2%) were diagnosed in a total of 583 woman. The ovarian tumors were type I in 134 cases (27.5%), type II in 325 cases (66.7%), and contained elements of both type I and type II tumors in 28 cases (5.7%). Most tubal and primary peritoneal cases, however, were type II tumors: 24 (96.0%) and 64 (90.1%), respectively. Only 16 (5.8%) of the ovarian high-grade serous carcinomas were stage I at diagnosis, whereas 240 (86.6%) were stage III+. Overall survival varied between the subtypes when matched for stage. Stage III low-grade serous and high-grade serous carcinomas had a significantly better survival compared to clear cell and mucinous cases,P= 0.0134. There was no significant difference in overall survival between the high-grade serous ovarian, tubal, or peritoneal carcinomas when matched for stage (stage III,P= 0.3758; stage IV,P= 0.4820).ConclusionsType II tumors are more common than type I and account for most tubal and peritoneal cancers. High-grade serous carcinomas, whether classified as ovarian/tubal/peritoneal, seem to behave as one disease entity with no significant difference in survival outcomes, therefore supporting the proposition of a separate classification of “tubo-ovarian serous carcinoma”.

High-grade serous carcinoma arising in a low-grade serous carcinoma and micropapillary serous borderline tumour of the ovary in a 23-year-old woman

2009 ◽  
Vol 54 (6) ◽  
pp. 771-773 ◽  
Author(s):  
M Ruhul Quddus ◽  
Lanita B Rashid ◽  
Katrine Hansen ◽  
C James Sung ◽  
W Dwayne Lawrence
Keyword(s):  
Serous Carcinoma ◽  
Low Grade ◽  
High Grade ◽  
Borderline Tumour

Prognostic significance of obesity in high-grade serous carcinoma of the ovary

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16528-e16528 ◽  
Author(s):  
M. Schlumbrecht ◽  
D. Urbauer ◽  
D. Gershenson ◽  
R. Broaddus
Keyword(s):  
Ovarian Cancer ◽  
Body Mass Index ◽  
Overall Survival ◽  
Body Mass ◽  
Neoadjuvant Treatment ◽  
The United States ◽  
Wilcoxon Test ◽  
Serous Carcinoma ◽  
Low Grade ◽  
High Grade

e16528 Background: Obesity is an epidemic public health problem in the United States. In gynecologic oncology, obesity is an established risk factor for endometrial cancer. However, its role in the pathogenesis and survival in ovarian cancer is debated. Recent studies have attempted to elucidate a possible relationship, but variations in design and heterogeneity in patient characteristics make it difficult to draw definitive conclusions. The purpose of our study was to determine if body mass index at the time of treatment initiation for high grade serous ovarian carcinoma has an effect on patient outcome. Methods: Nine-hundred four patients treated for ovarian cancer at M.D. Anderson Cancer Center were identified between 2002 and 2007. Patients were excluded for low grade or non-serous histology, neoadjuvant treatment, or if presenting with recurrent disease. Clinicopathologic data were extracted by retrospective chart review. Patients were stratified by body mass index (BMI) as normal (BMI<25), overweight (BMI 25-<30), or obese (BMI>30). All were treated with primary cytoreduction and standard platinum/taxane chemotherapy. Chemotherapy was dosed using adjusted body weights. Outcomes included time to recurrence, overall survival, success of surgical debulking, and chemotherapeutic toxicities. Statistical analysis was performed using Fisher's exact test, Wilcoxon test, and Kaplan-Meier estimates. Results: A total of 127 patients were included for analysis. Patients were followed for a mean of 37 months (range 3–86 months). Twenty-one patients were obese (16.5%), and 35 were overweight (27.5%). Diabetes was more prevalent in the obese cohort (p = 0.0038). There was a trend towards greater likelihood of suboptimal debulking in obese patients, but this did not reach statistical significance (p = 0.06). BMI had no effect on recurrence-free survival (HR 0.69 [CI 0.39–1.23], p = 0.21) or overall survival (HR 0.95 [CI 0.68–2.43], p = 0.91). There was no difference in chemotherapy side effects or chemoresistance across BMI strata. Conclusions: Body mass index has no effect on survival in women with high grade serous ovarian cancer. Effectively managing comorbidities and ensuring adequate chemotherapy dosing in the obese patient is crucial for optimizing outcome. No significant financial relationships to disclose.

Cancer Stem Cell–Related Marker NANOG Expression in Ovarian Serous Tumors: A Clinicopathological Study of 159 Cases

2017 ◽  
Vol 27 (9) ◽  
pp. 2006-2013 ◽  
Author(s):  
Nataša Kenda Šuster ◽  
Snježana Frković Grazio ◽  
Irma Virant-Klun ◽  
Ivan Verdenik ◽  
Špela Smrkolj
Keyword(s):  
Stem Cell ◽  
Cancer Stem Cell ◽  
Signal Intensity ◽  
Serous Carcinoma ◽  
Low Grade ◽  
Clinical Parameters ◽  
High Grade ◽  
Ovarian Serous Carcinoma ◽  
Nanog Expression ◽  
Serous Tumors

ObjectiveThe objectives of this study were to assess cancer stem cell–related marker NANOG expression in ovarian serous tumors and to evaluate its prognostic significance in relation to ovarian serous carcinoma.MethodsNANOG protein expression was immunohistochemically evaluated in the ovarian tissue microarrays of 20 patients with benign ovarian serous tumors, 30 patients with borderline ovarian serous tumors, and 109 patients with ovarian serous carcinomas, from which 106 were of high-grade and 3 of low-grade morphology Immunohistochemical reaction was scored according to signal intensity and the percentage of positive cells in tumor samples. Pursuant to our summation of signal intensity and positive cell occurrence, we divided our samples into 4 groups: NANOG-negative, NANOG–slightly positive, NANOG–moderately positive, and NANOG–strongly positive group. Complete clinical data were obtained for the ovarian serous carcinoma group, and correlation between clinical data and NANOG expression was analyzed.ResultsA specific brown nuclear, or cytoplasmic reaction, was considered a positive NANOG staining. In terms of the ovarian serous carcinoma group, 69.7% were NANOG positive, 22.9% slightly positive, 22.9% moderately positive, and 23.9% strongly positive. All NANOG-positive cases were of high-grade morphology. Benign and borderline tumors and low-grade serous carcinomas were NANOG negative. There was no significant correlation between NANOG expression and clinical parameters in terms of the ovarian serous carcinoma group.ConclusionsPositive NANOG expression is significantly associated with high-grade ovarian serous carcinoma and is absent in benign, borderline, and low-grade serous lesions. In our study, there was no correlation between NANOG expression and clinical parameters, including its use in the prognosis of ovarian serous carcinoma.

scholarly journals DNA Damage Response is Prominent in Ovarian High-Grade Serous Carcinomas, Especially Those with Rsf-1 (HBXAP) Overexpression

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Malti Kshirsagar ◽  
Wei Jiang ◽  
Ie-Ming Shih
Keyword(s):  
Dna Damage ◽  
Chromatin Remodeling ◽  
Dna Damage Response ◽  
Surrogate Marker ◽  
Serous Carcinoma ◽  
Low Grade ◽  
High Grade ◽  
Significant Difference ◽  
Damage Response ◽  
Microenvironmental Stress

DNA damage commonly occurs in cancer cells as a result of endogenous and tumor microenvironmental stress. In this study, we applied immunohistochemistry to study the expression of phosphorylated Chk2 (pChk2), a surrogate marker of the DNA damage response, in high grade and low grade of ovarian serous carcinoma. A phospho-specific antibody specific for threonine 68 of Chk2 was used for immunohistochemistry on a total of 292 ovarian carcinoma tissues including 250 high-grade and 42 low-grade serous carcinomas. Immunostaining intensity was correlated with clinicopathological features. We found that there was a significant correlation between pChk2 immunostaining intensity and percentage of pChk2 positive cells in tumors and demonstrated that high-grade serous carcinomas expressed an elevated level of pChk2 as compared to low-grade serous carcinomas. Normal ovarian, fallopian tube, ovarian cyst, and serous borderline tumors did not show detectable pChk2 immunoreactivity. There was no significant difference in pChk2 immunoreactivity between primary and recurrent high-grade serous carcinomas. In high-grade serous carcinomas, a significant correlation (P<0.0001) in expression level (both in intensity and percentage) was found between pChk2 and Rsf-1 (HBXAP), a gene involved in chromatin remodeling that is amplified in high-grade serous carcinoma. Our results suggest that the DNA damage response is common in high-grade ovarian serous carcinomas, especially those with Rsf-1 overexpression, suggesting that Rsf-1 may be associated with DNA damage response in high-grade serous carcinomas.

scholarly journals High Grade Serous Carcinoma Presenting as a Huge Pelvic Mass with Normal Looking Ovaries: A Diagnostic Challenge for Pathologist

2020 ◽  
Author(s):  
Vaishali Walke ◽  
Amrapali Gaikwad ◽  
Madiha Shaikh ◽  
Balwant Kowe
Keyword(s):  
Correct Diagnosis ◽  
Diagnostic Delay ◽  
Delayed Diagnosis ◽  
Pelvic Mass ◽  
Clinical Findings ◽  
Serous Carcinoma ◽  
High Grade ◽  
Diagnostic Challenge ◽  
Immunohistochemical Markers ◽  
Specific Symptoms

High-grade serous carcinoma represents 50-60% of all ovarian cancers and is the most common type of malignant surface epithelial tumour. Serous carcinoma is often diagnosed in the sixth and seventh decade, while the mean age for high-grade tumours is 63 year. It’s not only the non-specific symptoms like vague abdominal pain, nausea, gastrointestinal disturbances, but also the unusual presentation which is responsible for delayed diagnosis. This diagnostic delay can become the reason for increased mortality, despite advances in surgical management and chemotherapy. Here, authors discuss a case of 60-year-old postmenopausal women who presented with a huge pelvi-peritoneal mass and with grossly normal ovaries. Considering clinical findings and histomorphology, the possibility of malignant mesothelioma was considered as the first differential diagnosis; however extensive sampling of ovaries and supportive immunohistochemical markers helped us to arrive at a definitive diagnosis. The present case emphasises the importance of extensive tissue sampling and ancillary techniques in arriving at a correct diagnosis.

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