scholarly journals Molecular stratification of endometrioid ovarian carcinoma predicts clinical outcome

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Robert L. Hollis ◽  
John P. Thomson ◽  
Barbara Stanley ◽  
Michael Churchman ◽  
Alison M. Meynert ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Ovarian Carcinoma ◽  
Molecular Taxonomy ◽  
Figo Stage ◽  
Molecular Heterogeneity ◽  
Molecular Stratification ◽  
Genomic Complexity ◽  
Molecular Therapeutics ◽  
Whole Exome ◽  
Endometrioid Ovarian Carcinoma

Abstract Endometrioid ovarian carcinoma (EnOC) demonstrates substantial clinical and molecular heterogeneity. Here, we report whole exome sequencing of 112 EnOC cases following rigorous pathological assessment. We detect a high frequency of mutation in CTNNB1 (43%), PIK3CA (43%), ARID1A (36%), PTEN (29%), KRAS (26%), TP53 (26%) and SOX8 (19%), a recurrently-mutated gene previously unreported in EnOC. POLE and mismatch repair protein-encoding genes were mutated at lower frequency (6%, 18%) with significant co-occurrence. A molecular taxonomy is constructed, identifying clinically distinct EnOC subtypes: cases with TP53 mutation demonstrate greater genomic complexity, are commonly FIGO stage III/IV at diagnosis (48%), are frequently incompletely debulked (44%) and demonstrate inferior survival; conversely, cases with CTNNB1 mutation, which is mutually exclusive with TP53 mutation, demonstrate low genomic complexity and excellent clinical outcome, and are predominantly stage I/II at diagnosis (89%) and completely resected (87%). Moreover, we identify the WNT, MAPK/RAS and PI3K pathways as good candidate targets for molecular therapeutics in EnOC.

scholarly journals Molecular stratification of endometrioid ovarian carcinoma predicts clinical outcome

2020 ◽  
Author(s):  
Robert L Hollis ◽  
John P Thomson ◽  
Barbara Stanley ◽  
Michael Churchman ◽  
Alison M Meynert ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Ovarian Carcinoma ◽  
Molecular Taxonomy ◽  
Figo Stage ◽  
Low Complexity ◽  
Molecular Stratification ◽  
Molecular Therapeutics ◽  
Genomic Study ◽  
Endometrioid Ovarian Carcinoma ◽  
Novel Target

AbstractEndometrioid ovarian carcinoma (EnOC) is an under-investigated type of ovarian carcinoma. Here, we report the largest genomic study of EnOCs to date, performing whole exome sequencing of 112 cases following rigorous pathological assessment. High frequencies of mutation were detected in CTNNB1(43%), PIK3CA(43%), ARID1A(36%), PTEN(29%), TP53(26%) and SOX8(19%), a novel target of recurrent mutation in EnOC. POLE and mismatch repair protein-encoding genes were mutated at lower frequency (6%, 18%) with significant co-occurrence. A molecular taxonomy was constructed using a novel algorithm (PRISTINE), identifying clinically distinct EnOC subtypes: TP53m cases demonstrated greater genomic complexity, were frequently FIGO stage III/IV at diagnosis (48%) and incompletely debulked (44%), and demonstrated inferior survival; conversely, CTNNB1m cases demonstrated low complexity and excellent clinical outcome, were predominantly stage I/II at diagnosis (89%) and completely resected (87%). Tumour complexity provides further resolution within the TP53wt/CTNNB1wt group. Moreover, we identify the WNT, MAPK/RAS and PI3K pathways as good candidate targets for molecular therapeutics in EnOC.

Molecular Heterogeneity of Endometrioid Ovarian Carcinoma

2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Susanna Leskela ◽  
Ignacio Romero ◽  
Juan M. Rosa-Rosa ◽  
Tamara Caniego-Casas ◽  
Eva Cristobal ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Molecular Heterogeneity ◽  
Endometrioid Ovarian Carcinoma

Immunohistochemical expression of p53, bcl-2, and p21WAF1/CIP1 in early cervical carcinoma: Correlation with clinical outcome

2002 ◽  
Vol 12 (3) ◽  
pp. 290-298 ◽  
Author(s):  
M Graflund ◽  
B Sorbe ◽  
M Karlsson
Keyword(s):  
Survival Rate ◽  
Clinical Outcome ◽  
Cervical Carcinoma ◽  
Early Stage ◽  
Tumor Grade ◽  
Figo Stage ◽  
Immunohistochemical Expression ◽  
Cancer Specific Survival ◽  
Term Survival ◽  
Cervical Carcinomas

Abstract.Graflund M, Sorbe B, Karlsson M. Immunohistochemical expression of p53, bcl-2, and p21 WAF1/CIP1 in early cervical carcinoma: Correlation with clinical outcome.The objective of this study was to assess the value of p53, bcl-2, and p21WAF1/CIP1 immunoreactivity as predictors of pelvic lymph node metastases (LNM), recurrences, and death due to the disease in early stage (FIGO I-II) cervical carcinomas. FIGO stage, type of histopathology, and tumor grade were also evaluated in this series of patients treated by radical hysterectomy (Wertheim-Meigs) between 1965 and 1990. A total of 172 patients were included. A tumor was regarded as positive when more than 30% of the neoplastic cells exhibited immunoreactivity. Positive immunostaining was found in 8.9% for p53, in 43.5% for bcl-2, and in 25.0% for p21WAF1/CIP1. None of them was able to predict LNM or clinical outcome. Presence of LNM, tumor recurrence, and death from disease were significantly associated with the FIGO stage (P = 0.014, P = 0.009, and P = 0.001, respectively). The 5-year cancer-specific survival rate was 91.6% and the overall survival rate was 90.5%. It was concluded that immunohistochemically detected p53, bcl-2, and p21WAF1/CIP1 appeared to be of no predictive value with regard to LNM, tumor recurrences, or long-term survival in early cervical carcinomas.

scholarly journals Integrated molecular characterisation of endometrioid ovarian carcinoma identifies opportunities for stratification

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Robert L. Hollis ◽  
Barbara Stanley ◽  
John P. Thomson ◽  
Michael Churchman ◽  
Ian Croy ◽  
...  
Keyword(s):  
High Risk ◽  
Ovarian Carcinoma ◽  
Expression Patterns ◽  
Parp Inhibitors ◽  
Receptor Expression ◽  
Cancer Type ◽  
Sequencing Data ◽  
Molecular Features ◽  
Endometrioid Ovarian Carcinoma ◽  
Molecular Landscape

AbstractEndometrioid ovarian carcinoma (EnOC) is an under-investigated ovarian cancer type. Recent studies have described disease subtypes defined by genomics and hormone receptor expression patterns; here, we determine the relationship between these subtyping layers to define the molecular landscape of EnOC with high granularity and identify therapeutic vulnerabilities in high-risk cases. Whole exome sequencing data were integrated with progesterone and oestrogen receptor (PR and ER) expression-defined subtypes in 90 EnOC cases following robust pathological assessment, revealing dominant clinical and molecular features in the resulting integrated subtypes. We demonstrate significant correlation between subtyping approaches: PR-high (PR + /ER + , PR + /ER−) cases were predominantly CTNNB1-mutant (73.2% vs 18.4%, P < 0.001), while PR-low (PR−/ER + , PR−/ER−) cases displayed higher TP53 mutation frequency (38.8% vs 7.3%, P = 0.001), greater genomic complexity (P = 0.007) and more frequent copy number alterations (P = 0.001). PR-high EnOC patients experience favourable disease-specific survival independent of clinicopathological and genomic features (HR = 0.16, 95% CI 0.04–0.71). TP53 mutation further delineates the outcome of patients with PR-low tumours (HR = 2.56, 95% CI 1.14–5.75). A simple, routinely applicable, classification algorithm utilising immunohistochemistry for PR and p53 recapitulated these subtypes and their survival profiles. The genomic profile of high-risk EnOC subtypes suggests that inhibitors of the MAPK and PI3K-AKT pathways, alongside PARP inhibitors, represent promising candidate agents for improving patient survival. Patients with PR-low TP53-mutant EnOC have the greatest unmet clinical need, while PR-high tumours—which are typically CTNNB1-mutant and TP53 wild-type—experience excellent survival and may represent candidates for trials investigating de-escalation of adjuvant chemotherapy to agents such as endocrine therapy.

Delay in adjuvant chemotherapy administration for patients with FIGO stage I epithelial ovarian carcinoma is associated with worse survival

2021 ◽  
Vol 162 ◽  
pp. S124
Author(s):  
Dimitrios Nasioudis ◽  
Spyridon Mastroyannis ◽  
Emily Ko ◽  
Ashley Haggerty ◽  
Lori Cory ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Ovarian Carcinoma ◽  
Figo Stage ◽  
Epithelial Ovarian Carcinoma ◽  
Stage I ◽  
Chemotherapy Administration

scholarly journals Retinoblastoma pathway deregulatory mechanisms determine clinical outcome in high-grade serous ovarian carcinoma

2013 ◽  
Vol 27 (7) ◽  
pp. 991-1001 ◽  
Author(s):  
Anca Milea ◽  
Sophia HL George ◽  
Donco Matevski ◽  
Haiyan Jiang ◽  
Mary Madunic ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Ovarian Carcinoma ◽  
High Grade ◽  
Serous Ovarian Carcinoma

scholarly journals PO-0746: Clinical outcome of carbon ion radiotherapy for FIGO stage IVA uterine cervical cancer

2015 ◽  
Vol 115 ◽  
pp. S369-S370 ◽  
Author(s):  
S. Shiba ◽  
M. Wakatsuki ◽  
S. Kato ◽  
T. Ohno ◽  
K. Karasawa ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Clinical Outcome ◽  
Figo Stage ◽  
Uterine Cervical Cancer ◽  
Carbon Ion Radiotherapy ◽  
Carbon Ion

Randomized trial comparing two combination chemotherapy regimens (CHAP-5 v CP) in advanced ovarian carcinoma.

1987 ◽  
Vol 5 (8) ◽  
pp. 1157-1168 ◽  
Author(s):  
J P Neijt ◽  
W W ten Bokkel Huinink ◽  
M E van der Burg ◽  
A T van Oosterom ◽  
P H Willemse ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Therapeutic Index ◽  
Residual Tumor ◽  
Figo Stage ◽  
Gynecology And Obstetrics ◽  
Adequate Hydration ◽  
Karnofsky Index

One hundred ninety-one patients with advanced epithelial ovarian carcinoma were treated with either a combination of doxorubicin and a five-day course of cisplatin alternating with cyclophosphamide and hexamethylmelamine orally for 14 days (CHAP-5) or cyclophosphamide and cisplatin both administered intravenously (IV) on a single day at 3-week intervals (CP). At a median follow-up time of 45 months, treatment with each of these combinations resulted in the same remission rates (80% and 74%, respectively) and exactly the same progression-free survival and overall survival (median, 26 months). Despite adequate hydration, more renal toxicity was encountered in the CP-treated patients than in those who received CHAP-5. Disabling neurotoxicity and severe myelosuppression were encountered more frequently in the patients treated with CHAP-5. Because the toxicity was lower and CP treatment required shorter hospitalization, the single-day regimen was considered preferable for future use. The Karnofsky index was the only independent predictor for response, whereas both this index and the size of residual tumor before chemotherapy were predictive of survival. After correcting for other prognostic factors, it was determined that tumor size associated with improved survival was less than 1 cm. The site of metastases in International Federation of Gynecology and Obstetrics (FIGO) stage IV patients did not influence survival within this category. The results of this study confirm our previous findings that patients with microscopic remnants at second-look have a survival similar to that of patients who are histopathologically free of disease. This makes the significance of so-called pathologically confirmed complete remission questionable. The survival benefit of debulking surgery performed during chemotherapy seems only minimal for patients in whom debulking has already been attempted before treatment. Like others, we have found the CP regimen to have a good therapeutic index.

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