BRCA1 Immunohistochemical Staining as a Prognostic Indicator in Uterine Serous Carcinoma

2013 ◽  
Vol 23 (1) ◽  
pp. 113-118 ◽  
Author(s):  
James P. Beirne ◽  
Jennifer E. Quinn ◽  
Perry Maxwell ◽  
Steve E. Kalloger ◽  
Jessica McAlpine ◽  
...  
Keyword(s):  
Protein Expression ◽  
Progression Free Survival ◽  
Prognostic Indicator ◽  
Serous Carcinoma ◽  
Nuclear Staining ◽  
Cell Nuclei ◽  
Brca1 Protein ◽  
Free Survival ◽  
Response To Chemotherapy ◽  
Uterine Serous Carcinoma

ObjectivesThe objective of this study was to investigate the relationship between BRCA1 protein expression, as determined by immunohistochemistry, and clinical outcome in uterine serous carcinoma (USC).MethodsA tissue microarray containing duplicate cores of 73 cases of USC was immunohistochemically stained with mouse anti-BRCA1 (Ab-1) mouse monoclonal (MS110) antibody. The cores were scored in a semiquantitative manner evaluating both the distribution and intensity of nuclear staining. BRCA1 protein expression was correlated with progression-free survival.ResultsSeventy-two of 73 cases were assessable, and there was a statistically significant decreased progression-free survival for those cases exhibiting tumor cell nuclei staining of 76% or greater (P = 0.0023).ConclusionsOur study illustrates that a low level of BRCA1 protein expression is a favorable prognostic indicator in USC, similar to what is observed in high-grade serous ovarian carcinoma. Further studies should focus on the BRCA1 status of USCs at a molecular level and also investigate whether BRCA1 protein expression is associated with response to chemotherapy in USC.

Expression and prognostic significance of kallikrein-related peptidase 8 protein levels in advanced ovarian cancer by using automated quantitative analysis

2009 ◽  
Vol 101 (03) ◽  
pp. 541-546 ◽  
Author(s):  
Andreas Scorilas ◽  
Sonia Markakis ◽  
Diane Kowalski ◽  
Robert L. Camp ◽  
Eleftherios P. Diamandis ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Survival Analysis ◽  
Protein Expression ◽  
Prognostic Significance ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Protein Analysis ◽  
Free Survival ◽  
Response To Chemotherapy

SummaryKallikrein-related peptidases, a subgroup of the serine protease enzyme family, are considered to be important prognostic biomarkers in cancer. In this study we sought to determine the prognostic value of kallikrein-related peptidase 8 (KLK8,hK8,KLK-8) in ovarian cancer using a novel method of compartmentalised in situ protein analysis. A tissue array composed of 150 advanced stage ovarian cancers, uniformly treated with surgical debulking followed by platinum-paclitaxel combination chemotherapy, was constructed. For the evaluation of kallikrein-related peptidase 8 protein expression, we used an immunofluorescence-based method of automated in situ quantitative protein analysis (AQUA). Mean follow-up time of the cohort was 34.35 months. One hundred twenty-six of 150 cases had sufficient tissue for AQUA analysis. There were significant correlations between tumour mask KLK8 protein expression levels and clinicopathological variables, including grade (p=0.0011), residual disease (p=0.0063) and clinical response to chemotherapy(p=0.0346). In univariate survival analysis there was a significant correlation between KLK8 tumour mask expression and five years progression-free survival, meanwhile it was not associated with five-year overall survival (p =0.0694). Specifically, low KLK8 expression correlated with better outcome (top vs. bottom quartile, p=0.0319). In multivariate survival analysis, adjusting for well-characterised prognostic variables, tumour KLK8 expression level retained its prognostic significance for progression-free survival (95%CI: 0.341–1.027, p=0.045). The possibility that KLK8 may be a suitable candidate as a diagnostic and prognostic marker warrants further investigation.

WT1 expression associated with platinum-sensitivity and improved progression-free survival in uterine serous carcinoma

2021 ◽  
Vol 162 ◽  
pp. S337-S338
Author(s):  
Jennifer McEachron ◽  
Nancy Zhou ◽  
Agha Wajdan Baqir ◽  
Absia Jabbar ◽  
Kyra Gassmann ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Serous Carcinoma ◽  
Free Survival ◽  
Platinum Sensitivity ◽  
Uterine Serous Carcinoma

scholarly journals Randomized Phase II Trial of Carboplatin-Paclitaxel Versus Carboplatin-Paclitaxel-Trastuzumab in Uterine Serous Carcinomas That Overexpress Human Epidermal Growth Factor Receptor 2/neu

2018 ◽  
Vol 36 (20) ◽  
pp. 2044-2051 ◽  
Author(s):  
Amanda N. Fader ◽  
Dana M. Roque ◽  
Eric Siegel ◽  
Natalia Buza ◽  
Pei Hui ◽  
...  
Keyword(s):  
Phase Ii Trial ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Serous Carcinoma ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Randomized Phase Ii ◽  
Control Versus ◽  
Epidermal Growth ◽  
Uterine Serous Carcinoma

Purpose Uterine serous carcinoma is a rare, aggressive variant of endometrial cancer. Trastuzumab is a humanized monoclonal antibody that targets human epidermal growth factor receptor 2 (HER2)/neu, a receptor overexpressed in 30% of uterine serous carcinoma. This multicenter, randomized phase II trial compared carboplatin-paclitaxel with and without trastuzumab in patients with advanced or recurrent uterine serous carcinoma who overexpress HER2/neu. Methods Eligible patients had primary stage III or IV or recurrent HER2/neu-positive disease. Participants were randomly assigned to receive carboplatin-paclitaxel (control arm) for six cycles with or without intravenous trastuzumab (experimental arm) until progression or unacceptable toxicity. The primary end point was progression-free survival, which was assessed for differences between treatment arms via one-sided log-rank tests. Results From August 2011 to March 2017, 61 patients were randomly assigned. Forty progression-free survival–related events occurred among 58 evaluable participants. Among all patients, median progression-free survival was 8.0 months (control) versus 12.6 months (experimental; P = .005; hazard ratio [HR], 0.44; 90% CI, 0.26 to 0.76). Similarly, median progression-free survival was 9.3 (control) versus 17.9 (experimental) months among 41 patients with stage III or IV disease undergoing primary treatment ( P = .013; HR, 0.40; 90% CI, 0.20 to 0.80) and 6.0 (control) versus 9.2 months (experimental), respectively, among 17 patients with recurrent disease ( P = .003; HR, 0.14; 90% CI, 0.04 to 0.53). Toxicity was not different between treatment arms, and no unexpected safety signals emerged. Conclusion Addition of trastuzumab to carboplatin-paclitaxel was well tolerated and increased progression-free survival. These encouraging results deserve further investigation to determine their impact on overall survival in patients with advanced or recurrent uterine serous carcinoma who overexpress HER2/neu.

scholarly journals High expression of the p53 isoform γ is associated with reduced progression-free survival in uterine serous carcinoma

BMC Cancer ◽  
2018 ◽  
Vol 18 (1) ◽  
Author(s):  
Katharina Bischof ◽  
Stian Knappskog ◽  
Ingunn Stefansson ◽  
Emmet Martin McCormack ◽  
Jone Trovik ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
High Expression ◽  
Serous Carcinoma ◽  
Free Survival ◽  
Uterine Serous Carcinoma

scholarly journals Carboplatin and vincristine chemotherapy for children with newly diagnosed progressive low-grade gliomas

1997 ◽  
Vol 2 (3) ◽  
pp. E1
Author(s):  
Roger J. Packer ◽  
Joanne Ater ◽  
Jeffrey Allen ◽  
Peter Phillips ◽  
Russell Geyer ◽  
...  
Keyword(s):  
Objective Response ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Response To Treatment ◽  
Low Grade ◽  
Significant Prognostic Factor ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Low Grade Gliomas ◽  
Response To Chemotherapy

The optimum treatment of nonresectable low-grade gliomas of childhood remains undecided. There has been increased interest in the use of chemotherapy for young children, but little information concerning the long-term efficacy of such treatment. Seventy-eight children with a mean age of 3 years (range 3 months-16 years) who had newly diagnosed, progressive low-grade gliomas were treated with combined carboplatin and vincristine chemotherapy. The patients were followed for a median of 30 months from diagnosis, with 31 patients followed for more than 3 years. Fifty-eight children had diencephalic tumors, 12 had brainstem gliomas, and three had diffuse leptomeningeal gliomas. Forty-four (56%) of 78 patients showed an objective response to treatment. Progression-free survival rates were 75 ± 6% at 2 years and 68 ± 7% at 3 years. There was no statistical difference in progression-free survival rates between children with neurofibromatosis Type 1 and those without the disease (2-year, progression-free survival 79 ± 11% vs. 75 ± 6%, respectively). The histological subtype of the tumor, its location, and its maximum response to chemotherapy did not have an impact on the duration of disease control. The only significant prognostic factor was age: children 5 years old or younger at the time of treatment had a 3-year progression-free survival rate of 74 ± 7% compared with a rate of 39 ± 21% in older children (p < 0.01). Treatment with carboplatin and vincristine is effective, especially in younger children, in controlling newly diagnosed progressive low-grade gliomas.

scholarly journals Protein kinase C isozymes; predictors of progression free survival in NSCLC patients

2019 ◽  
Author(s):  
Ann Rita Halvorsen ◽  
Mads Haugland Haugen ◽  
Åsa Kristina Öjlert ◽  
Marius Lund-Iversen ◽  
Lars Jørgensen ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Protein Expression ◽  
Molecular Subtypes ◽  
Progression Free Survival ◽  
Free Survival ◽  
Kinase C ◽  
Pkc Isozymes ◽  
Pkc Β ◽  
Low Expression

Abstract Background Protein expression is deregulated in cancer, and the proteomic changes observed in lung cancer may be a consequence of mutations in essential genes. The purpose of this study was to identify protein expression associated with prognosis in lung cancers stratified by smoking status, molecular subtypes, and EGFR-, TP53- and KRAS-mutations. Methods We performed profiling of 295 cancer-relevant phosphorylated and non-phosphorylated proteins, using reverse phase protein arrays. Biopsies from 80 patients with operable lung adenocarcinomas were analyzed for protein expression and association with progression free survival (PFS) were studied. Results Spearman rank correlation analysis identified 56 proteins with significant association to PFS (p<0.05). High expression of protein kinase C (PKC)-α and the phosporylated state of PKC-α, PKC-β and PKC-δ, showed the strongest positive correlation to PFS, especially in the wild type samples. This was confirmed in gene expression data from 186 samples. Based on protein expression, unsupervised hierarchical clustering separated the samples into four subclusters enriched with the molecular subtypes TRU, PI or PP (p=0.0001). Subcluster 2 contained a smaller cluster (2a) enriched with samples of the subtype PP, low expression of the PKC isozymes, and associated with poor PFS (p=0.003) compared to the other samples. Subcluster 2a revealed increased expression of neuroendocrine markers, supporting the aggressive behavior. Low expression of the PKC isozymes in the subtype PP and a reduced relapse free survival was confirmed with the TCGA LUAD samples. Conclusion This study identified different proteins associated with PFS depending on molecular subtype, smoking- and mutational-status, with PKC-α, PKC-β and PKC-δ showing the strongest correlation. Cluster analysis detected a subgroup of samples enriched for samples of the PP subtype and poor PFS, which may benefit from a more aggressive treatment regimen.

scholarly journals Correlation of PKM2 and CD44 Protein Expression with Poor Prognosis in Platinum-Treated Epithelial Ovarian Cancer: A Retrospective Study

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1013
Author(s):  
Chara Papadaki ◽  
Stavroula Manolakou ◽  
Eleni Lagoudaki ◽  
Spyros Pontikakis ◽  
Despo Ierodiakonou ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Prognostic Factor ◽  
Protein Expression ◽  
Epithelial Ovarian Cancer ◽  
Cancer Cells ◽  
Progression Free Survival ◽  
Free Survival ◽  
Protein Levels ◽  
Low Expression

CD44, a surface marker for cancer stem cells, interacts with PKM2, a key regulator of aerobic glycolysis, and enhances the glycolytic phenotype of cancer cells leading to antioxidant protection and macromolecules’ synthesis. To clarify the clinical importance of this “cross-talk” as a mechanism of drug resistance, we assessed the expression both of PKM2 and of CD44 in cancer cells of patients with epithelial ovarian cancer (EOC) treated with platinum-based treatment. One hundred and seventy-one patients with EOC were assessed for PKM2mRNA expression and PKM2 and CD44 proteins detection. Associations with progression-free survival (PFS) and overall survival (OS) were assessed with Kaplan–Meier and adjusted Cox regression models. PKM2mRNA and protein as well as CD44 protein were detectable in the majority of patients. Positive correlation between PKM2 and CD44 protein expression was observed (Spearman rho = 0.2, p = 0.015). When we used the median to group patients into high versus low expression, high PKM2mRNA and protein levels were significantly associated with lower progression-free survival (PFS; p = 0.003 and p = 0.002, respectively) and shorter overall survival (OS; p ≤ 0.001 and p = 0.001, respectively). However, high CD44 protein expression was significantly correlated only with shorter OS (p = 0.004). Moreover, patients with both high PKM2 and CD44 protein levels experienced shorter PFS and OS (p = 0.007 and p = 0.003, respectively) compared to patients with low expression of both proteins. Finally, higher PKM2mRNA and protein expression as well as CD44 protein expression (HR: 2.16; HR: 1.82; HR: 1.01, respectively) were independent prognostic factors for decreased median OS (mOS), whereas only PKM2 protein expression (HR: 1.95) was an independent prognostic factor for decreased median PFS (mPFS). In conclusion, PKM2 expression is a negative prognostic factor in EOC patients, but the interaction between CD44 and PKM2 that may be implicated in EOC platinum-resistance needs further investigation.

scholarly journals Expression of the cancer stem cell marker SSEA1 is associated with poor survival in metastatic high-grade serous carcinoma

2020 ◽  
Vol 477 (5) ◽  
pp. 677-685
Author(s):  
Ben Davidson ◽  
Arild Holth ◽  
Hiep Phuc Dong
Keyword(s):  
Stem Cell ◽  
Survival Analysis ◽  
Cancer Stem Cell ◽  
Ovarian Carcinoma ◽  
Progression Free Survival ◽  
Stem Cell Marker ◽  
Serous Carcinoma ◽  
High Grade ◽  
Poor Survival ◽  
Free Survival

Abstract The objective of the present study was to perform a quantitative analysis of cancer stem cell (CSC) marker expression in ovarian carcinoma effusions. The clinical role of SSEA1 in metastatic high-grade serous carcinoma (HGSC) was additionally analyzed. CD133, Nanog, SOX2, Oct3/4, SSEA1, and SSEA4 protein expressions were quantitatively analyzed using flow cytometry (FCM) in 24 effusions. SSEA1 expression by immunohistochemistry was analyzed in 384 HGSC effusions. Highly variable expression of CSC markers by FCM was observed, ranging from 0 to 78% of Ber-EP4-positive cells in the case of CD133, with the largest number of negative specimens seen for SSEA4. SSEA1 expression by immunohistochemistry was found in HGSC cells in 336/384 (89%) effusions, most commonly focally (< 5% of cells). SSEA1 was overexpressed in post-chemotherapy disease recurrence specimens compared with chemo-naïve HGSC effusions tapped at diagnosis (p = 0.029). In univariate survival analysis, higher SSEA1 expression was significantly associated with poor overall survival (p = 0.047) and progression-free survival (p = 0.018), though it failed to retain its prognostic role in Cox multivariate survival analysis in which it was analyzed with clinical parameters (p = 0.059 and p = 0.111 for overall and progression-free survival, respectively). In conclusion, CSC markers are variably expressed in ovarian carcinoma effusions. SSEA1 expression is associated with disease progression and poor survival in metastatic HGSC. Silencing this molecule may have therapeutic relevance in this cancer.

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