scholarly journals Evaluation of E-cadherin, β-catenin and vimentin protein expression using quantitative immunohistochemistry in nasopharyngeal carcinoma patients

2014 ◽  
Vol 37 (5) ◽  
pp. 320 ◽  
Author(s):  
Desirée Hao ◽  
Tien Phan ◽  
Amanda Jagdis ◽  
Jodi E Siever ◽  
Alexander C Klimowicz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Protein Expression ◽  
Disease Free Survival ◽  
Aberrant Expression ◽  
Free Survival ◽  
Mesenchymal Transition ◽  
Quantitative Immunohistochemistry ◽  
Increased Risk ◽  
Disease Free ◽  
E Cadherin

Purpose: Aberrant expression of proteins involved in epithelial-to-mesenchymal transition have been described in various cancers. In this retrospective study, we sought to evaluate E-cadherin, β-catenin and vimentin protein expression in non-metastatic nasopharyngeal (NPC) patients treated with curative intent, examine their relationship with each other, and with clinical outcome measures. Methods: Pre-treatment formalin-fixed paraffin-embedded biopsies of 140 patients treated between January 2000 and December 2007 were assembled into a tissue microarray (TMA). Automated quantitative immunohistochemistry (AQUA®) was performed on sequential TMA sections stained with fluorescent-labeled antibodies against E-cadherin, β-catenin and vimentin. Cox proportional hazards regression was used to estimate the effect of cytoplasmic vimentin, cytoplasmic E-cadherin, β-catenin nuclear/cytoplasmic ratio expression on overall survival and disease-free survival. Results: The average age of the patients was 51.7 years (SD=12.1; range 18-85), 66% were male, 71% had a KPS ≥ 90% at the start of treatment and 65% had stage III/IV disease. After adjusting for performance status, WHO and stage, high E-cadherin levels over the 75th percentile were found to produce a significantly increased risk for both a worse overall survival (HR = 2.53, 95% CI 1.21, 5.27) and disease free survival (DFS; HR = 2.14, 95%CI 1.28, 3.59). Vimentin levels over the first quartile produced an increased risk for a worse DFS (HR = 2.21, 95% CI 1.11, 4.38). No association was seen between β-catenin and survival. Conclusion: In this cohort of NPC patients, higher levels of E-cadherin and higher levels of vimentin were associated with worse outcomes. Further work is needed to understand the role of these epithelial mesenchymal transition proteins in NPC.

Nonmyeloablative Conditioning and Hematopoietic Cell Transplantation (HCT) from HLA-Matched Related or Unrelated Donors for Chemotherapy-Refractory Chronic Lymphocytic Leukemia (CLL).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2323-2323
Author(s):  
Mohamed Sorror ◽  
Michael Maris ◽  
Barry Storer ◽  
Brenda Sandmaier ◽  
Monic Stuart ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Gvhd ◽  
Disease Free Survival ◽  
Cerebral Stroke ◽  
Phase Ii Trials ◽  
Free Survival ◽  
Increased Risk ◽  
Unrelated Donors ◽  
Disease Free

Abstract Sixty-four patients (pts) with chemotherapy-refractory CLL who were ineligible for ablative allogeneic HCT due to age and/or comorbidities were given nonablative-HCT from related (n=44) or unrelated donors (n=20) between 1997-2003 (Table). Median pt age was 56 (range 44–69) years, interval from diagnosis to HCT was 4.4 (3–25) years, and number of prior regimens was 4 (range 1–12). Sixty-one pts were refractory to at least 1 regimen, 56 to fludarabine (FLU), 19 to alkylating agents, 14 to rituxumab and 4 to CAMPATH, and 2 had failed autologous HCT. Twenty-three pts (36%) had disease responsive to last chemotherapy [28% partial (PR) and 8% complete remission (CR)] while 34 were nonresponsive and 7 had untested relapse. Conditioning for HCT consisted of 2 Gy TBI alone (n=11) or combined with FLU (n=53), 90 mg/m2. Postgrafting immunosuppression consisted of mycophenolate mofetil and cyclosporine. Pts received G-CSF mobilized peripheral blood mononuclear cells. After HCT, pts became neutropenic for a median of 11 days. Forty-four percent of pts had thrombocytopenia (<20,000 cells/ul). Three pts had graft rejection; 1 died with aplasia and 2 are alive with disease relapse. Incidences of grades II, III, and IV acute GVHD were 39%, 14%, and 2% respectively, and chronic GVHD was 50% at 2-years. With median follow up of 24 (range 2.8–62.8) months, the overall response rate was 67% (50% in CR). URD-pts had significantly higher CR rate than MRD-pts. All 11 responding patients tested had molecular eradication of their disease. Overall, 39 patients are alive; 25 in CR, 5 in PR, 2 with stable disease, and 7 with relapse/progression. Twenty-five pts died, 10 from progression, 10 from infections ± GVHD, 2 from cardiac causes, 1 from metastatic lung cancer, 1 from cerebral stroke and 1 from rejection and aplasia. Estimated 2-year rates of non-relapse mortality, disease free survival, and overall survival were 22%, 52%, and 60% respectively. In multivariate analysis, high pretransplant comorbidity scores predicted higher non-relapse mortality and worse survival while bulky lymphadenopathy predicted increased risk of progression. CLL appears susceptible to graft-versus-leukemia effects particularly after URD grafts and nonablative-HCT should be explored in phase II trials in pts with FLU-refractory CLL. Table: Results Related (n = 44) Unrelated (n = 20) P Acute GVHD grade II, III, and IV 39%, 11%, and 2% 40%, 20%, and 0% 0.41 2-year chronic extensive GVHD 44% 69% 0.56 Median follow up (range) 31 (3–63) months 12 (3–39) months CR at 2-years 42% 78% 0.005 Relapse/progression at 2 years 34% 5% 0.08 Surviving pts 13 CR, 3 PR, 2 stable, 5 progression, 1 relapse 12 CR, 2 PR, 1 relapse 2-year non-relapse mortality 22% 20% 0.75 2-year disease free survival 44% 75% 0.15 2-year overall survival 56% 74% 0.33

scholarly journals Automated Quantification of CD44, c-MET, EGFR, MTOR, and GLUT1 Expression in Head and Neck Squamous Cell Carcinoma: The Impact of p16 Status and Response to Chemoradiation

2020 ◽  
pp. 1-10
Author(s):  
George Wilson ◽  
Jessica D. Arden ◽  
Thomas J. Quinn ◽  
Thomas G. Wilson ◽  
Alaa Hanna ◽  
...  
Keyword(s):  
Overall Survival ◽  
Protein Expression ◽  
Head And Neck ◽  
Squamous Cell ◽  
Disease Free Survival ◽  
Locoregional Control ◽  
Free Survival ◽  
Automated Quantification ◽  
Control Disease ◽  
Disease Free

This study assessed automated quantification of CD44, c-MET, MTOR, EGFR, and GLUT1 protein expression in a tissue microarray of 109 Stage II-IV p16 positive and negative head and neck squamous cell carcinomas (HNSCC) treated with definitive chemoradiation. Immunohistochemistry-based protein expression was quantified in an automated manner using digitally scanned images processed with Definiens Tissue Studio software to generate a histologic score (H-score, range 0-300) which was normalized for each biomarker. Biomarker expression levels were correlated with one another and with p16 status. Effects of biomarker and p16 status on locoregional control, disease-free survival, and overall survival were analyzed using Kaplan Meier and Cox proportional hazard modelling. There was a significant negative correlation between CD44 and p16 expression and significant positive correlations between CD44 and MTOR, CD44 and GLUT1, c-MET and MTOR, and MTOR and GLUT1. When patients were stratified by p16 status, the significant positive correlation between CD44 expression and MTOR remained for both the p16 positive and negative subsets, while correlations between CD44 and GLUT1 and c-MET and MTOR were seen in the p16 negative subset only. A significant correlation between MTOR and GLUT was seen overall and for the p16 positive subset. When the effects of biomarker expression on clinical endpoints were examined, histologic scores below the defined cut-points for CD44 and c-MET were each associated with improved locoregional control. Higher expressions of CD44, c-MET, EGFR, and GLUT1 were associated with inferior disease-free and overall survival. On multivariable analysis, p16 positivity remained independently associated with improved locoregional control, disease-free survival, and overall survival, high CD44 remained independently associated with inferior locoregional control, disease-free survival, and overall survival, and EGFR with inferior disease-free and overall survival. In conclusion, the use of an automated system to quantify IHC expression allowed objective correlation between biomarkers and stratification of patients, revealing that higher expressions of CD44, c-MET, EGFR, and GLUT1 were associated with poorer disease-free and overall survival.

scholarly journals Programmed death ligand-1 protein expression difference in basal like and non-basal like triple negative breast cancer and its association with disease free survival and overall survival: A systematic review

2021 ◽  
Vol 15 (2) ◽  
Author(s):  
Freda Halim ◽  
Hasrayati Agustina ◽  
Yohana Azhar ◽  
Bethy Hernowo
Keyword(s):  
Overall Survival ◽  
Protein Expression ◽  
Disease Free Survival ◽  
Risk Of Bias ◽  
Secondary Outcome ◽  
Original Research ◽  
Free Survival ◽  
Expression Difference ◽  
Disease Free

The study aims to summarize the literature and explore the strength of evidence for PD-L1 expression difference in basal like TNBC and non-basal like TNBC, and association of PD-L1 expression with disease free survival and overall survival in each group. A systematic search of the original research literature through November 29th, 2020, reported according to PRISMA guideline. Eligible studies investigated must have a primary outcome and at least one secondary outcome. Two reviewers independently searched, selected, and assessed quality of studies and risk of bias. Any discrepancies will be resolved by consensus or by consulting a third and fourth author. A total of 6813 articles were screened from which five articles were selected and assessed for quality of studies and risk of bias. Of 5 articles, no similar findings are found regarding the level of PD-L1 expression and its correlation with recurrence and overall survival. There is not enough substantial evidence to support the difference PD-L1 protein expression level in basal and non-basal like TNBC and its association with recurrence and overall survival. Hence, further studies are needed specifically to focus on this problem.

Diabetes as a predictor of colon cancer prognosis: A single institution based retrospective data analysis.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14709-e14709
Author(s):  
Nischala Ammannagari ◽  
Anush V. Patel ◽  
Eric N. Bravin ◽  
Melissa Scribani ◽  
Jennifer Victory
Keyword(s):  
Diabetes Mellitus ◽  
Colon Cancer ◽  
Overall Survival ◽  
Disease Free Survival ◽  
Small Sample ◽  
Diabetic Patients ◽  
Free Survival ◽  
Cancer Management ◽  
Increased Risk ◽  
Disease Free

e14709 Background: Prevalence of Diabetes mellitus (DM) has increased in dramatic proportions globally over last few decades. Several observational epidemiological studies have shown increased risk of colorectal malignancies in patients with DM. However, it is not yet clearly understood if DM can impact the prognosis of colon cancer. Methods: The hospital’s cancer registry was used to identify advanced (stage III or IV) colon cancer cases diagnosed from January 2007 to December 2009. To be included in the study, the patient must have been treated with a 5-Fluoro Uracil based chemotherapy regimen. Retrospective chart review of electronic medical records was used to collect patient characteristics, including diabetes mellitus (DM) status. Kaplan-Meier curves were constructed for disease free survival and overall survival time. These survival curves were compared between diabetics and non-diabetics using the log rank test. Results: A total of 40 subjects met inclusion criteria, with a mean age of 64.6 years. Compared to non-diabetic patients, patients with diabetes had significantly poorer disease free survival (p=0.03). There was no difference in overall survival when comparing diabetic patients to non-diabetics (p=0.47). Conclusions: While taking into consideration that the study was under powered due to the small sample size, this study does raise the possibility that diabetes mellitus might be an important prognostic indicator of colon cancer. Management of diabetes must be emphasized as an integral part of care of colon cancer.

High Expression of Ubiquitin C-terminal Hydrolase L1 Is Associated With Poor Prognosis in Endometrial Cancer Patients

2018 ◽  
Vol 28 (4) ◽  
pp. 675-683 ◽  
Author(s):  
Kohshiro Nakao ◽  
Takashi Hirakawa ◽  
Hiroto Suwa ◽  
Kayoko Kogure ◽  
Sadatomo Ikeda ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
Protein Expression ◽  
Messenger Rna ◽  
Poor Prognosis ◽  
Disease Free Survival ◽  
Rna Expression ◽  
Free Survival ◽  
Metastatic Lesions ◽  
Disease Free

ObjectiveThe ubiquitin C-terminal hydrolase L1 (UCHL1) plays a key role in tumor invasion and metastasis. Ubiquitin C-terminal hydrolase L1 is overexpressed in various cancers and reported to be correlated with a poor prognosis. The objective of this study was to determine the prognostic significance of UCHL1 in endometrial cancer.MethodsThe expression of UCHL1 in endometrial cancer was assessed using quantitative reverse transcription polymerase chain reaction and immunohistochemistry in 56 and 215 resected tumor specimens, respectively.ResultsThe 4-year survival rates of the high UCHL1 messenger RNA expression group and high UCHL1 protein expression group were 78% and 71%, respectively, compared with 96% and 95% for the low UCHL1 messenger RNA expression group and low UCHL1 protein expression group, respectively. Kaplan-Meier and log-rank tests indicated a significant correlation between expression of UCHL1 and disease-free survival and overall survival. Moreover, multivariate stepwise Cox proportional hazard regression model analysis showed that UCHL1 was a significant independent marker for predicting a poor disease-free survival and overall survival. In 43 patients with metastatic lesions, immunohistochemical analysis of metastatic lesions revealed that the recurrence rate and mortality rate were 62% and 41%, respectively, in 29 UCHL1-positive patients and 36% and 29%, respectively, in 14 UCHL1-negative patients.ConclusionsThe results of this study suggest that high UCHL1 expression is a strong marker of poor prognosis of endometrial cancer. Furthermore, we suggest that UCHL1 may be involved in the development of distant metastasis in endometrial cancer.

Comparison of clinical outcomes between enucleation and regular pancreatectomy in patients with non-functional pancreatic neuroendocrine tumors: a retrospective multicenter and propensity score-matched study

2021 ◽  
Author(s):  
Zhen Yang ◽  
Hengjun Gao ◽  
Jun Lu ◽  
Zheyu Niu ◽  
Huaqiang Zhu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Postoperative Complications ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Neuroendocrine Tumors ◽  
Disease Free Survival ◽  
Pancreatic Neuroendocrine Tumors ◽  
Free Survival ◽  
Estimated Blood Loss ◽  
Disease Free

Abstract Objective There are limited data from retrospective studies on whether therapeutic outcomes after regular pancreatectomy are superior to those after enucleation in patients with small, peripheral and well-differentiated non-functional pancreatic neuroendocrine tumors. This study aimed to compare the short- and long-term outcomes of regular pancreatectomy and enucleation in patients with non-functional pancreatic neuroendocrine tumors. Methods Between January 2007 and July 2020, 227 patients with non-functional pancreatic neuroendocrine tumors who underwent either enucleation (n = 89) or regular pancreatectomy (n = 138) were included. Perioperative complications, disease-free survival, and overall survival probabilities were compared. Propensity score matching was performed to balance the baseline differences between the two groups. Results The median follow-up period was 60.76 months in the enucleation group and 43.29 months in the regular pancreatectomy group. In total, 34 paired patients were identified after propensity score matching. The average operative duration in the enucleation group was significantly shorter than that in the regular pancreatectomy group (147.94 ± 42.39 min versus 217.94 ± 74.60 min, P < 0.001), and the estimated blood loss was also significantly lesser (P < 0.001). The matched patients who underwent enucleation displayed a similar overall incidence of postoperative complications (P = 0.765), and a comparable length of hospital stay (11.12 ± 3.90 days versus 9.94 ± 2.62 days, P = 0.084) compared with those who underwent regular pancreatectomy. There were no statistically significant differences between the two groups in disease-free survival and overall survival after propensity score matching. Conclusion Enucleation in patients with non-functional pancreatic neuroendocrine tumors was associated with shorter operative time, lesser intraoperative bleeding, similar overall morbidity of postoperative complications, and comparable 5-year disease-free survival and overall survival when compared with regular pancreatectomy.

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