Uterine Carcinomas in Tetrabromobisphenol A–exposed Wistar Han Rats Harbor IncreasedTp53Mutations and Mimic High-grade Type I Endometrial Carcinomas in Women

Women with endometrial carcinomas that express PD-L1 may respond better to immunotherapy. Our aim was to investigate the differential characteristics of PDL1–positive endometrial carcinomas and the prognostic significance of PDL1. We performed a retrospective chart review of 231 women with endometrial carcinomas who were managed at King Hussein Cancer Center (2007–2016) and performed immunohistochemistry for MLH1, PMS2, MSH2, MSH6, p53, and PD-L1. Overall, 89 cases (38.5%) were MMR-deficient. PD-L1 was expressed in 49 cases (21.2%) and its expression was significantly associated with MLH1/PMS2 deficiency (p = 0.044) but not MSH2/MSH6 deficiency (p = 0.59). p53 was mutant in 106 cases (46.5%), and its mutation was significantly associated with MMR proficiency (p < 0.001) but not PDL1 expression (p = 0.78). In women with endometrioid adenocarcinomas, PD-L1 expression was significantly associated with the Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) grade (p = 0.008). Overall, PDL1 expression did not significantly predict overall survival in unadjusted or adjusted analyses (p = 0.92 and 0.54, respectively). In conclusion, tumors with MLH1/PMS2 loss and high-grade endometrioid adenocarcinomas were more likely to express PDL1 in tumor cells. Further research is required to investigate whether the presence of either characteristic signals a higher likelihood of a favorable response if immunotherapy is administered.

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Low-calorie marmalades

Acta periodica technologica ◽

10.2298/apt0334023p ◽

2003 ◽

pp. 23-30 ◽

Cited By ~ 2

Author(s):

Sasa Pavlovic ◽

Aleksandra Tepic ◽

Biserka Vujicic

Keyword(s):

Sensory Evaluation ◽

Insulin Dependent Diabetes ◽

Locust Bean Gum ◽

Type I ◽

High Grade ◽

Type Ii ◽

Low Calorie ◽

Insulin Dependent ◽

Locust Bean ◽

Diabetes Melitus

The number of people suffering from insulin-dependent (Diabetes Melitus type I) and insulin-independent (Diabetes Melitus type II) is huge, and the number of potential diseased is in permanent rise. For that reason products with reduced amount of sugar have become very popular. Factory "Srbijanka" Valjevo manufactures reduced?sugar marmalades from apricot peach, strawberry, apple and orange. Low?metoxyl pectins and high-grade locust bean gum were used as gelation agents. Sensory evaluation and energy value of these marmalades were determined and all samples were highly graded. All marmalades belonged to the group of low-calorie (dietetic) products.

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KS02.4.A Olaparib in Recurrent IDH-mutant High-Grade Glioma (OLAGLI)

Neuro-Oncology ◽

10.1093/neuonc/noab180.011 ◽

2021 ◽

Vol 23 (Supplement_2) ◽

pp. ii4-ii4

Author(s):

F Ducray ◽

M Sanson ◽

O Chinot ◽

M Fontanilles ◽

R Rivoirard ◽

...

Keyword(s):

Median Time ◽

High Grade Glioma ◽

Median Number ◽

Parp Inhibition ◽

Low Grade ◽

Type I ◽

High Grade ◽

Rano Criteria ◽

Anaplastic Gliomas ◽

New Treatments

Abstract BACKGROUND There is a need to develop new treatments in IDH-mutant high-grade gliomas recurring after radiotherapy and chemotherapy. Based on preclinical studies showing that IDH-mutant tumors could be vulnerable to PARP inhibition we launched a phase II study to test the efficacy of olaparib (Lynparza) monotherapy in this population. METHODS Adults with recurrent high-grade IDH-mutant gliomas after radiotherapy and at least one line of alkylating chemotherapy (PCV or TMZ), KPS > 60, normal organ function were enrolled. The primary endpoint was 6 months PFS according to RANO criteria. Patients were treated with olaparib 300 mg twice daily. We used a single-stage Fleming design with p0 = 30%, p1 = 50%, a type I unilateral error rate of 5% and a power of 80%. RESULTS 35 patients with recurrent IDH-mutant gliomas (IDH1R132H-mutant n = 32, other IDH mutation n = 3, 1p/19 codeleted n = 16, 1p/19q non-codeleted n = 14) were enrolled (malignantly transformed low-grade gliomas n = 21, anaplastic gliomas n = 8, glioblastomas n = 6). Median time since diagnosis was 7.4 years (1–22 years), median time since radiotherapy was 2.8 years (0.6–18 years), median number of previous chemotherapy lines was 2 (1–5). With a median follow-up of 11 months, 30 patients had stopped treatment due to tumor progression and 2 patients were still on treatment 16 to 18 months after treatment start. At 6 months, 11/35 patients were progression-free (31 %). According to RANO criteria, based on local investigator analysis, 2 patients (5%) had a partial response and 14 patients a stable disease (37%) with a median duration of response of 9 months (4–18+). Median PFS and OS were 2.3 and 15.9 months and were similar in 1p/19q codeleted and non-codeleted patients. A grade 3 olaparib-related adverse event was observed in 5 patients (14%, lymphopenia n = 3, fatigue n = 2, diarrhea n = 1) and a grade 2 in 15 patients (43%), most frequently consisting in fatigue (23%), gastrointestinal disorders (20%) and lymphopenia (20%). No patient definitively stopped olaparib due to side effects. CONCLUSIONS In this heavily pre-treated population of recurrent IDH-mutant gliomas, olaparib monotherapy was well tolerated and resulted in some activity supporting its evaluation in association with alkylating chemotherapy in recurrent IDH-mutant gliomas in future studies.

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A Comparison of Death Domain-Associated Protein 6 in Different Endometrial Carcinomas Histotypes

Biomarker Insights ◽

10.1177/1177271919864892 ◽

2019 ◽

Vol 14 ◽

pp. 117727191986489

Author(s):

Cao Jin ◽

Sean Hacking ◽

Miglena K Komforti ◽

Mansoor Nasim

Keyword(s):

Clear Cell ◽

Point Mutations ◽

Low Grade ◽

Nuclear Staining ◽

High Grade ◽

Death Domain ◽

Gynecology And Obstetrics ◽

Grade 3 ◽

Histologic Types ◽

Endometrial Carcinomas

Background: Death domain-associated protein 6 (DAXX) is involved in regulating apoptosis via subcellular localization. The presence of DAXX point mutations correlates well with loss of nuclear expression on immunohistochemistry (IHC). In this study, we sought to determine (1) whether DAXX expression pattern is the same across different uterine carcinoma subtypes, and (2) which uterine carcinomas show loss of nuclear DAXX IHC. Design: We studied 65 uterine carcinomas of the following histologic types: 30 endometrioid (12 FIGO [The International Federation of Gynecology and Obstetrics] grade 1, 12 FIGO grade 2, and 6 FIGO grade 3), 8 serous, 14 clear cell, and 13 undifferentiated/dedifferentiated type (UEC/DDEC). Nuclear DAXX IHC was assessed in each tumor and was graded semi-quantitatively as follows: 0% to 50%, 50% to 75%, and greater than 75% of lesional cells react. Results: A total of 61% (25/41) of high-grade carcinomas (FIGO grade 3, serous, clear cell, and UEC/DDEC]) showed retained DAXX nuclear staining in >75% of lesional cells, compared with only 4.2% (1/24) of the low-grade carcinomas (FIGO grades 1 and 2) ( P = .0001), where DAXX expression was cytoplasmic. In addition, in the 11 DDEC cases, all the differentiated components showed loss of nuclear DAXX compared with the undifferentiated components which retained nuclear DAXX expression. Conclusions: We demonstrate that loss of nuclear DAXX is present in low-grade endometrial carcinomas and the differentiated components in UEC/DDEC, but not in high-grade ones, suggesting DAXX’s role in tumor progression and its potential as a therapeutic target in high-grade endometrial carcinomas.

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

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000477 ◽

2015 ◽

Vol 25 (7) ◽

pp. 1201-1207 ◽

Cited By ~ 9

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”.

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Abstract B05: Induction of DNA damage in high-grade serous carcinoma induces type I interferon signaling

10.1158/1557-3265.ovca19-b05 ◽

2020 ◽

Author(s):

Danielle E. Bolland ◽

Yuning Hao ◽

Yee Sun Tan ◽

Jake Reske ◽

Lijun Tan ◽

...

Keyword(s):

Dna Damage ◽

Type I Interferon ◽

Serous Carcinoma ◽

Type I ◽

High Grade ◽

Interferon Signaling

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Type II endometrial cancers: original research on a series

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20172300 ◽

2017 ◽

Vol 6 (6) ◽

pp. 2306

Author(s):

B. L. Nayak ◽

Sujata Misra ◽

Suryakant Jaysingh ◽

S. K. Giri

Keyword(s):

Clear Cell ◽

Myometrial Invasion ◽

Serous Carcinoma ◽

Original Research ◽

Clear Cell Adenocarcinoma ◽

Type I ◽

Type Ii ◽

Clinicopathological Analysis ◽

Hematoxylin And Eosin ◽

Endometrial Carcinomas

Background: Endometrial carcinoma, which ranks 3rd in India amongst the gynecological malignancies, is of two histological types: I and II. These differ in molecular as well as in clinical and histopathological profiles. Type II is estrogen independent, nonendometrioid, with higher grade histologies, more aggressive and carries an adverse prognosis.Methods: Endometrial carcinomas diagnosed from endometrial biopsies and hysterectomy specimens in the Dept of Gynaec-oncology, AHRCC, Cuttack from November 2009 to January 2015 were included in the study. All specimens were fixed in 10% neutral buffered formalin and paraffin embedded for histological examination with hematoxylin and eosin staining. The clinicopathological analysis of the cases of EC was done with an emphasis on morphology.Results: Of a total of 150 cases of EC reported, 20 cases were classified as type II EC (13.33%) as per histology. The age of the patients ranged from 36 to 73 years, with mean age is 61 years. In 11 cases (55%), the myometrial invasion was more than half. the histological type was a clear cell adenocarcinoma in 50% of the cases. All were treated with hysterectomy and chemotherapy.Conclusions: Of the type II EC, serous carcinoma is the most common type. Clinical presentation and prognosis differs in comparison to type I EC, thus the recognition of this type of EC is pivotal.

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High-Grade Endometrial Carcinomas

Surgical Pathology Clinics ◽

10.1016/j.path.2019.02.003 ◽

2019 ◽

Vol 12 (2) ◽

pp. 343-362 ◽

Cited By ~ 3

Author(s):

Joseph W. Carlson ◽

Denis Nastic

Keyword(s):

High Grade ◽

Endometrial Carcinomas

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