ACTN4 gene amplification and actinin-4 protein overexpression drive tumour development and histological progression in a high-grade subset of ovarian clear-cell adenocarcinomas

2012 ◽  
Vol 60 (7) ◽  
pp. 1073-1083 ◽  
Author(s):  
Sohei Yamamoto ◽  
Hitoshi Tsuda ◽  
Kazufumi Honda ◽  
Masashi Takano ◽  
Seiichi Tamai ◽  
...  
Keyword(s):  
Gene Amplification ◽  
Clear Cell ◽  
High Grade ◽  
Protein Overexpression ◽  
Tumour Development ◽  
Histological Progression

No Strong Association Between HER-2/neu Protein Overexpression and Gene Amplification in High-grade Invasive Urothelial Carcinomas

2008 ◽  
Vol 14 (3) ◽  
pp. 261-266 ◽  
Author(s):  
Vildan Caner ◽  
Nilay Sen Turk ◽  
Fusun Duzcan ◽  
N. Lale Satiroglu Tufan ◽  
E. Canan Kelten ◽  
...  
Keyword(s):  
Gene Amplification ◽  
Strong Association ◽  
High Grade ◽  
Protein Overexpression ◽  
Urothelial Carcinomas ◽  
Her 2

HER2 gene amplification and protein overexpression in uterine clear cell carcinoma and its implications in targeted immunotherapy.

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 29-29
Author(s):  
Jain Zhou ◽  
William R. Sukov ◽  
Jodi M Carter ◽  
J. Kenneth Schoolmeester
Keyword(s):  
Gene Amplification ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Her2 Overexpression ◽  
Her2 Expression ◽  
Her2 Amplification ◽  
Protein Overexpression ◽  
Her2 Gene ◽  
Her2 Gene Amplification ◽  
Uterine Clear Cell Carcinoma

29 Background: Uterine clear cell carcinoma (UCCC) is a high-grade endometrial carcinoma. The current treatment is hysterectomy with post-operative chemotherapy and/or radiation. The 5-year disease free survival remains dismal for UCCC with 65% for early-stage and 54% for advanced stage disease. In addition, UCCC may be more resistant to chemotherapy or radiation therapy than the endometrioid subtype. The aim of the current study is to investigate the HER2 gene amplification status in UCCC and its role for targeted therapy in UCCC. Methods: Twenty-nine cases of UCCC were retrieved from surgical pathology archives of Mayo Clinic at Rochester between 2011 and 2015. All cases except one case were hysterectomy specimens. The blocks contain the most characteristic morphology of UCCC were selected and corresponding paraffin sections were subjected to fluorescent in situ hybridization for amplification of HER2 gene (Hercept, Abbott Molecular) and parallel immunohistochemical (IHC) study. Results: A total of 9 (of 29; 31%) UCCCs showed HER2 amplification and 4 (of 29; 14%) were considered equivocal for HER2 amplification by FISH. A total of 3 (10%) tumors showed 3+ HER2 overexpression while 11 (38%) UCCCs showed 2+ HER2 overexpression, 9 (31%) showed 1+ expression with the remaining cases showing no expression of HER2. Importantly, we observed significant intratumoral heterogeneity with regard to HER2 expression. Comparing the results of IHC with HER2 gene status as determined by FISH, 2 (66%) of the 3 cases that showed 3+ HER2 expression also showed amplification for HER2 by FISH, while 1 (33%) was equivocal for HER2 amplification. Of the 11 tumors that showed 2+ HER2 expression, 6 (55%) were amplified by FISH and 1 (9%) was equivocal. Conclusions: This is the largest number of UCCC cases that has been studied on the HER2 amplification and corresponding protein overexpression. Our results indicate that the HER2 overexpression is common in UCCCs and is frequently associated with HER2 amplification. These results also suggest that targeted adjuvant therapy with trastuzumab-based immunotherapy should be evaluated in patients with UCCC showing HER2 protein overexpression or HER2 gene amplification.

scholarly journals Clear Cell Carcinomas of the Mullerian System: Does the Pathogenesis Vary Depending on Their Nuclear Grade and Their Association with Endometriosis? An Immunohistochemical Analysis

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Ahmad Alduaij ◽  
Katrine Hansen ◽  
Tahreem A. Karim ◽  
Cunxian Zhang ◽  
Michelle M. Lomme ◽  
...  
Keyword(s):  
Clear Cell ◽  
Immunohistochemical Analysis ◽  
Nuclear Grade ◽  
High Grade ◽  
Ki 67 ◽  
High Nuclear Grade ◽  
Positive Immunostaining

Clear cell carcinomas (CCC) of the mullerian system are considered high grade tumors, but morphologically, the cells of CCC show both low and high grade features. The aims of the current study were to categorize CCC into low and high nuclear grade types, correlate their association with endometriosis, and then observe possible variations in pathogenesis based on their expression of p53 and Ki-67. We studied 41 pure mullerian CCCs and designated each as either a high (HNG) or low (LNG) nuclear grade tumor. Morphologically, 17 (41%) CCCs were LNG and 24 (59%) were HNG. Nine (38%) HNG and 2 (12%) LNG tumors showed positive immunostaining with p53. Endometriosis was associated with 8 (47%) LNG tumors and 8 (33%) HNG CCCs. Of the 11 cases with p53 alteration, 4 (1 LNG and 3 HNG) were associated with endometriosis. Conclusions: HNG CCCs, irrespective of their association with endometriosis, have alterations of p53. In general, LNG ovarian and endometrial CCCs, irrespective of their association with endometriosis/adenomyosis, are less likely to show p53 alteration. It appears that mullerian CCCs may have variable pathogenesis depending on their nuclear grade and association with endometriosis. A larger study is needed to validate these findings.

CT-based radiomic model predicts high grade of clear cell renal cell carcinoma

2018 ◽  
Vol 103 ◽  
pp. 51-56 ◽  
Author(s):  
Jiule Ding ◽  
Zhaoyu Xing ◽  
Zhenxing Jiang ◽  
Jie Chen ◽  
Liang Pan ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
High Grade ◽  
Cell Renal Cell Carcinoma

scholarly journals Prediction of High-Grade Clear Cell Renal Cell Carcinoma Based on Plasma mRNA Profiles in Patients with Localized Pathologic T1N0M0 Stage Disease

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1182
Author(s):  
Jee Soo Park ◽  
Hyo Jung Lee ◽  
Ahmad Almujalhem ◽  
Hatem Hamed Althubiany ◽  
Alqahatani Ali A ◽  
...  
Keyword(s):  
Renal Cell ◽  
Prediction Models ◽  
Clear Cell ◽  
Multivariate Logistic Regression Analysis ◽  
Mrna Levels ◽  
High Grade ◽  
Cell Renal Cell Carcinoma ◽  
Fuhrman Grade ◽  
Stage Disease ◽  
Tumor Tissues

A high nuclear grade is crucial to predicting tumor recurrence and metastasis in clear cell renal cell carcinomas (ccRCCs). We aimed to compare the mRNA profiles of tumor tissues and preoperative plasma in patients with localized T1 stage ccRCCs, and to evaluate the potential of the plasma mRNA profile for predicting high-grade ccRCCs. Data from a prospective cohort (n = 140) were collected between November 2018 and November 2019. Frozen tumor tissues and plasma were used to measure PBRM1, BAP1, SET domain-containing 2 (SETD2), KDM5C, FOXC2, CLIP4, AQP1, DDX11, BAIAP2L1, and TMEM38B mRNA levels, and correlation with the Fuhrman grade was investigated. Multivariate logistic regression analysis revealed significant association between high-grade ccRCC and SETD2 and DDX11 mRNA levels in tissues (odds ratio (β) = 0.021, 95% confidence interval (CI): 0.001–0.466, p = 0.014; β = 6.116, 95% CI: 1.729–21.631, p = 0.005, respectively) and plasma (β = 0.028, 95% CI 0.007–0.119, p < 0.001; β = 1.496, 95% CI: 1.187–1.885, p = 0.001, respectively). High-grade ccRCC prediction models revealed areas under the curve of 0.997 and 0.971 and diagnostic accuracies of 97.86% and 92.86% for the frozen tissue and plasma, respectively. SETD2 and DDX11 mRNA can serve as non-invasive plasma biomarkers for predicting high-grade ccRCCs. Studies with long follow-ups are needed to validate the prognostic value of these biomarkers in ccRCCs.

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

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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