HAGE (DDX43) protein expression as an independent biomarker of poor clinical outcome of breast cancer (BC) and potential as a therapeutic target for ER-negative BC.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1013-1013 ◽  
Author(s):  
Stephen Chan ◽  
Tarek M. A. Abdel-Fatah ◽  
Stephanie McArdle ◽  
Paul Moseley ◽  
Catherine Johnson ◽  
...  
Keyword(s):  
High Risk ◽  
Clinical Outcome ◽  
Protein Expression ◽  
Cox Regression ◽  
Positive Impact ◽  
Prospective Trial ◽  
Fold Increase ◽  
Distant Metastases ◽  
Poor Clinical Outcome ◽  
Risk Of Death

1013 Background: Recently, we have confirmed that HAGE is involved in promoting proliferation as assessed by increased thymidine incorporation and our preliminary results using shRNA to permanently knockdown HAGE expression also suggests the involvement of HAGE in tumor motility and metastasis. In this study we aimed to analyze the expression of HAGE in large well-characterized BC cohorts to determine its relationship with other clinico-pathological parameters and to investigate its prognostic value. Methods: HAGE protein expression was assessed in: a) 40 normal breast tissue (NBT), b) 60 invasive BCs and their matching NBT, c) BC cell lines, d) A series of 1650 consecutive cases of primary BC who treated with adjuvant CMF and/or endocrine therapies. Further validation was performed in 2 independent series of high risk ER- BC: a) 300 ER –BC who did not received any CT and b) 396 ER- BC treated with adjuvant anthracycline (ATC) based CT. Results: The NBT showed negative HAGE expression (HAGE-) throughout. HAGE overexpression (HAGE+) was observed in 10% of BC and was significantly associated with aggressive clinico-pathological features including: ER-, high grade and triple negative phenotypes. Moreover, HAGE+ expression showed an adverse outcome with a 2-4 fold increase in the risk of death, recurrence and metastases (ps<0.00001) compared to HAGE-; ps<0.0001. Using a multivariate Cox regression model including ER status, grade, size and tumour stage, HAGE expression was confirmed as a powerful independent prognostic factor (p<0.0001). The poor clinical outcome of HAGE+ was further confirmed in high risk (NPI>3.4) ER- patients who did not received any CT (p<0.0001). While, adjuvant CT either CMF or ATC had a positive impact on HAGE+/high risk ER- BC as HAGE+ had a similar risk of death, recurrence and distant metastases to HAGE- expression. Conclusions: This is the first report which shows HAGE to be a potential predictor for poor prognosis in BC patients, and may be an attractive novel target for molecular and vaccine therapy for those patients. A prospective trial of adjuvant chemotherapy/vaccine to confirm this finding is warranted.

scholarly journals c-Flip protein expression in Burkitt's lymphomas is associated with a poor clinical outcome

2005 ◽  
Vol 128 (6) ◽  
pp. 767-773 ◽  
Author(s):  
Marie-Blanche Valnet-Rabier ◽  
Bruno Challier ◽  
Sylvie Thiebault ◽  
Regis Angonin ◽  
Genevieve Margueritte ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Protein Expression ◽  
Poor Clinical Outcome

Postoperative PET/CT for detection of early recurrence (ER) after surgery for squamous cell carcinomas (SCC) of the oral cavity (OC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6060-6060
Author(s):  
Yao Yu ◽  
Heiko Schöder ◽  
Jung Kang ◽  
Sean Matthew McBride ◽  
C. Jillian Tsai ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
High Risk ◽  
Postoperative Radiotherapy ◽  
Prospective Trial ◽  
Disease Free Survival ◽  
Distant Metastases ◽  
Risk Groups ◽  
Free Survival ◽  
Pet Ct

6060 Background: Patients with ER after surgery and prior to postoperative radiation (RT) for SCC of the OC have aggressive biology and poor prognosis. After the introduction of a PET/CT simulator in our department, we incorporated post-operative PET/CT as part of RT planning. We hypothesized PET/CT would improve detection of macroscopic disease before postoperative RT. Methods: We reviewed the medical records of patients treated with postoperative radiotherapy between 2005 and 2019 for OC SCC. Clinicopathologic risk factors were recorded. Intermediate risk factors (IRFs) included pT3-4 disease, nodal disease, perineural invasion (PNI), lymphovascular invasion (LVI), and close ( < 5mm) surgical margins (SM); extranodal extension (ENE) and positive SM were considered high-risk factors (HRF). Patients were stratified into risk groups based upon the number and type of risk factors: 0-1 IRFs, 2 IRFs, ≥3 IRFs, and any HRF. Patients were considered to have ER if they had biopsy confirmed recurrence, or if the imaging or exam was sufficiently suspicious, after discussion with the head and neck team, to warrant treatment to definitive doses of RT (70 Gy). Results: Our cohort included 391 patients with SCC of the OCC who were treated with postoperative radiotherapy. 61% of patients were male, 35% had pT3-4 disease, 36% had pN2a-3 disease, 53% had PNI, 20% had LVI, 30% had ENE, and 14% had positive SM. The most common sites were oral tongue (46%), alveolar ridge (18%), and buccal mucosa (13%). 237 (61%) patients underwent postoperative PET/CT planning, and 165 patients (41%) were planned with CT only. Patients screened with post-operative PET/CT were more likely to be diagnosed with ER (46/237, 19.4%) than those simulated with CT only (6/154, 3.9%, p < 0.0001). Among patients simulated with PET/CT, 7%, 9%, 14%, and 35% of patients were diagnosed with ER for patients with 0-1 IRFs, 2 IRFs, ≥3 IRFs, and any HRF, respectively. Median follow-up was 4.1 years (95% CI 3.6 – 4.5). Among 52 patients with ER, 24 (49.0%) had local, 41 (83.7%) had regional, and 5 (10.2%) had distant recurrence. 17 (33%) of ER were biopsy proven. For patients with ER, 3-year freedom from locoregional recurrence, distant-metastasis free survival, and overall survival were 45.2% (95% CI 32% - 64%), 55% (95% CI 42% – 72%), and 43% (95% CI 30% - 61%), respectively. For patients without ER, use of postoperative PET/CT was associated with improved disease-free survival (HR 0.68, 95% CI 0.46 – 0.98, p = 0.041) and overall survival (HR 0.59, 95% CI 0.38 – 0.91, p = 0.019). Conclusions: Postoperative PET/CT may increase detection ER compared to CT simulation alone and improve risk stratification. Patients with ER are at high risk of locoregional failure, distant metastases, and mortality, despite salvage therapy. A prospective trial is underway at our institution to systemically study the role of PET/CT for detection of ER.

Study of genotypic variations and protein expression of the xCT subunit of cystine/glutamate transporter in pancreatic cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 210-210
Author(s):  
T. J. Huang ◽  
D. Li ◽  
Y. Li ◽  
S. P. Kar ◽  
S. Krishnan ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Protein Expression ◽  
Cox Regression ◽  
Performance Status ◽  
Glutamate Transporter ◽  
Supporting Evidence ◽  
Cox Regression Analysis ◽  
Risk Of Death ◽  
Increased Risk

210 Background: The plasma membrane xCT cystine-specific subunit of the cystine/glutamate transporter contributes to chemotherapy resistance in pancreatic cancer by regulating intracellular glutathione levels and protecting cancer cells against oxidative stress. We previously noted that the rs7674870 single nucleotide polymorphism (SNP) of xCT correlated with overall survival in pancreatic cancer and may be predictive of platinum resistance. There are no data regarding xCT protein expression in pancreatic cancer or the functional significance of this SNP. Methods: Paraffin-embedded core and surgical biopsy tumor specimens from 49 patients with metastatic pancreatic adenocarcinoma were analyzed by immunohistochemistry (IHC) using an xCT specific antibody (Novus Biologicals). xCT protein IHC expression scores (product of intensity and percentage of staining cells) were analyzed in relation to overall survival and genotype of the patients using the one factor ANOVA test, Kaplan-Meier plot, log-rank test, and Cox regression analysis. Overall survival was measured from the date of diagnosis to the date of death or last follow-up. Results: Positive xCT expression was detected in 38 (78%) of the 49 samples, and 9 (18%) patients had high levels of expression. High xCT expression was associated with lower overall survival as compared with low expression (5.1 months versus 8.8 months; p = 0.119). In a multivariate Cox regression model with adjustment for prognostic parameters of age, sex, performance status and CA19-9 level, high xCT expression was associated with a 2.1-fold increased risk of death (p = 0.096). Performance status also correlated with overall survival (p = 0.027). Preliminary analysis on the genotype-phenotype association (n = 12) indicated that xCT expression was higher with the TT genotype than the TC/CC genotype (p = 0.115), which is consistent with the previous observation that the TT genotype was associated with reduced survival. Conclusions: These data provide supporting evidence for a possible role of cystine/glutamate transporter xCT subunit in pancreatic cancer progression and survival. Further pharmacogenomic and clinicopathologic studies are ongoing. No significant financial relationships to disclose.

scholarly journals Renal dysfunction in patients with pulmonary embolism: data from the SIRENA register

2021 ◽  
Vol 26 (2S) ◽  
pp. 4422
Author(s):  
M. V. Menzorov ◽  
V. V. Filimonova ◽  
A. D. Erlikh ◽  
O. L. Barbarash ◽  
S. A. Berns ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
High Risk ◽  
Risk Stratification ◽  
Hospital Mortality ◽  
Renal Dysfunction ◽  
Cox Regression ◽  
Russian Population ◽  
Hospital Death ◽  
Death Risk ◽  
Risk Of Death

Aim. To assess the prevalence, severity and prognostic value of renal dysfunction (RD) in patients with pulmonary embolism (PE) of the Russian population, as well as to determine the RD significance as a marker that improves the predictive ability of current risk stratification systems.Material and methods. From April 2018 to April 2019, patients hospitalized due to PE were sequentially included in the Russian multicenter observational prospective registry SIRENA. RD was diagnosed at a glomerular filtration rate (GFR) <60 ml/ min/1,73 m2. Risk of early (hospital or 30-day) death was stratified in accordance with the current 2019 ESC Clinical Guidelines. During the study, we analyzed inpatient mortality and complication rate.Results. A total of 604 patients (men, 293 (49%); women, 311 (51%)) were in the study. RD was detected in 320 (53%) patients, while severe dysfunction — in 63 (10%) ones. In addition, 71 (12%) patients had high death risk, 364 (61%) — intermediate, 164 (27%) — low. During hospitalization, 107 (18%) patients died, including 32% from the high-risk group, 20% — moderate, and 7% — low. RD in the deceased patients was diagnosed more often, while GFR <50 ml/min/1,73 m2 reliably predicted hospital mortality (sensitivity, 67%; specificity, 72%; AUC=0,72; p<0,001). In patients with simplified Pulmonary Embolism Severity Index (sPESI) of 0 and ≥ 1, the presence of RD led to at least a 2-fold increase in mortality. Multivariate Cox regression revealed that RD is a predictor of in-hospital mortality (hazard ratio (HR), 3,41; 95% confidence interval (CI): 2,15-5,41; p<0,001), regardless of the presence of death risk reclassifies, such as high troponin (HR, 1,31; 95% CI: 0,80-2,14; p=0,28) and right ventricular dysfunction (HR, 1,23; 95% CI: 0,74-2,04; p=0,42).Conclusion. In patients with PE of the Russian population, there is a high incidence of RD, which is diagnosed in every second patient and is severe in 10% of cases. The presence of RD is associated with a significant increase in in-hospital mortality, while the risk of death increases with a decrease in GFR. The addition of RD, considered as a decrease in the estimated GFR <60 ml/min/1,73 m2, to the sPESI improves risk stratification and allows identification of patients at high risk of in-hospital death.

scholarly journals Prognostic value of Ki-67 in patients with hypertension and prostate cancer: A real-world study in a Chinese population

2020 ◽  
Author(s):  
Zhijun Cao ◽  
Mengqi Xiang ◽  
Zhiyu Zhang ◽  
Jianglei Zhang ◽  
Minjun Jiang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prognostic Value ◽  
Cox Regression ◽  
Cox Model ◽  
Prognostic Nutritional Index ◽  
Fold Increase ◽  
Lasso Regression ◽  
Ki 67 ◽  
Risk Of Death ◽  
Risk Of Progression

Abstract Background Prostate cancer is the second most common malignancy in males worldwide, with high mortality, especially when combined with hypertension. Ki-67 is one of the most reliable markers of growth for neoplastic human cell populations. However, the prognostic value of Ki-67 in patients with hypertension and prostate cancer remains unclear.Methods We retrospectively analyzed 296 patients with hypertension and prostate cancer from May 1, 2012, to October 1, 2015. The overall survival was evaluated by Cox regression models and Kaplan-Meier analysis. In addition, a nomogram was established, and the accuracy of the model was assessed by a calibration curve.Results A total of 101 (34.1%) patients died. In the multivariate analysis, being Ki-67(+) was associated with a >5-fold increase in the risk of death (hazard ratio [HR] 5.83, 95% confidence interval [CI] 3.35-10.14, p<0.001) and a 2-fold increase in the risk of progression (HR 2.06, 95% CI 1.37-3.10, p<0.001). Multivariate Lasso regression showed that smoking, heart failure, ACS, Ki-67 expression, serum albumin, prognostic nutritional index, surgery, Gealson score, and stage were positively associated with prognosis in patients with prostate cancer. To quantify the contribution of each covariate to the prognosis, a nomogram of the Cox model was generated. The nomogram demonstrated excellent accuracy in estimating the risk of death, with a bootstrap-corrected C index of 0.829. There was also a suitable calibration curve for risk estimation.Conclusions The presence of Ki-67 predicts worsened outcomes for overall mortality. A cross-validated multivariate score including Ki-67 had excellent concordance and efficacy for predicting prostate cancer.

scholarly journals Prognostic Value of Nodal Response After Preoperative Treatment of Gastric Adenocarcinoma

2019 ◽  
Vol 17 (2) ◽  
pp. 161-168 ◽  
Author(s):  
Yvonne H. Sada ◽  
Brandon G. Smaglo ◽  
Joy C. Tan ◽  
Hop S. Tran Cao ◽  
Benjamin L. Musher ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adjuvant Therapy ◽  
Cox Regression ◽  
Fold Increase ◽  
Preoperative Therapy ◽  
Preoperative Treatment ◽  
Disease Response ◽  
Risk Of Death ◽  
Postoperative Therapy ◽  
Node Positive

Background: Pathologically positive lymph nodes (ypN+) after preoperative chemotherapy are associated with poor survival in patients with gastric cancer. Little is known about the association between response to preoperative therapy and the benefit of postoperative therapy. Methods: This retrospective cohort study of the National Cancer Database included patients with clinically node-positive (cN+) gastric cancer treated with preoperative therapy followed by surgery (2006–2014). Preoperative treatment modality was categorized as the inclusion of radiation therapy (RT) or chemotherapy alone. Pretreatment clinical and pathologic stages were used to determine pathologic treatment response rates. The association between overall risk of death and preoperative treatment, disease response, and adjuvant therapy use was evaluated using multivariable Cox regression. Results: Preoperative RT was used in 53.6% of 1,976 patients with cN+ gastric cancer, (74.3% cardia and 10.1% noncardia). The nodal response rate was 38.9% and was higher with RT than with chemotherapy alone (cardia, 46.0% vs 29.1%; P<.001; noncardia, 43.8% vs 31.9%; P=.06). Preoperative RT was associated with an approximate 2-fold increase in the odds of pathologic response compared with chemotherapy. Overall, use of adjuvant therapy was not associated with a decreased risk of death. A primary tumor response with residual nodal disease was not associated with survival (hazard ratio [HR], 1.03; 95% CI, 0.66–1.60). However, a nodal response with residual primary disease was significantly associated with survival (HR, 0.54; 95% CI, 0.44–0.65). Conclusions: More than one-third of node-positive gastric cancers showed pathologic nodal response with preoperative treatment. RT is associated with a higher response than chemotherapy. Patients with ypN+ disease have worse survival, regardless of whether they receive postoperative therapy. Future gastric cancer trials should evaluate the role of preoperative RT and individualize postoperative therapy use.

Immunohistochemical Analysis of p18INK4C and p14ARF Protein Expression in 117 Oligodendrogliomas

2002 ◽  
Vol 126 (1) ◽  
pp. 42-48
Author(s):  
Andrey Korshunov ◽  
Andrey Golanov
Keyword(s):  
Clinical Outcome ◽  
Protein Expression ◽  
Color Image ◽  
Tumor Grade ◽  
World Health ◽  
Low Grade ◽  
Image Analyzer ◽  
Survival Times ◽  
Who Grade ◽  
Risk Of Death

Abstract Objective.—To investigate immunoexpression of 2 cyclin-dependent kinase inhibitors, p18INK4C (p18) and p14ARF (p14), in oligodendrogliomas and to evaluate the possible association with tumor grade and clinical outcome. Design.—One hundred seventeen specially selected cases of cerebral oligodendrogliomas were studied retrospectively. Tumor specimens were immunohistochemically examined with antibodies to p18INK4C (118.2) and p14ARF (FL-132) proteins. A computerized color image analyzer was used to count immunostained nuclei. Results.—p18 nuclear immunoexpression was found in 57 (49%) of the oligodendrogliomas we studied. p18 immunoreactivity exhibited a clear tendency to elevate with increasing tumor grade, and the mean p18 labeling index was 9.7% for low-grade (World Health Organization [WHO] grade II) and 19.2% for high-grade (WHO III) tumors. p14-immunopositive nuclei were found in 87 (74%) tumors, and p14 immunoreactivity showed no correlation with oligodendroglioma histological malignancy. Survival times were significantly reduced for p18-positive tumors, and risk of death was independently associated with p18 expression (hazard ratio = 2.48; P = .01). There was no difference in survival times in patients with or without p14 immunoreactivity. Conclusions.—p18 protein expression is closely associated with malignant oligodendrogliomas and worse clinical outcome. It seems unlikely that p14 immunohistochemistry will be of value in assessing individual prognosis for these tumors.

Abstract 12812: Leg Muscle Strength Independently Predicts Clinical Outcome In Patients With Acute Decompensated Heart Failure

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Je-Wook Park ◽  
Jong-Chan Youn ◽  
Jaewon Oh ◽  
Sungha Park ◽  
Sang-Hak Lee ◽  
...  
Keyword(s):  
Heart Failure ◽  
Muscle Strength ◽  
Clinical Outcome ◽  
Cox Regression ◽  
Acute Decompensated Heart Failure ◽  
Surrogate Marker ◽  
Decompensated Heart Failure ◽  
Poor Clinical Outcome ◽  
Cox Regression Analysis ◽  
Leg Muscle

Introduction: Leg muscle strength (LMS) could be an index of frailty in patients with heart failure. However, its prognostic value in patients with acute decompensated heart failure (ADHF) is not well investigated. Hypothesis: We hypothesized that impaired LMS was independently associated with poor clinical outcome in patients with ADHF. Methods: We measured LMS in 110 prospectively and consecutively enrolled ADHF patients (75 male, mean age 60 ± 14 years, mean ejection fraction 29.9 ± 14.6%) at predischarge period. Primary endpoint was cardiovascular (CV) events defined as CV mortality, cardiac transplantation or rehospitalization due to HF aggravation. Results: The CV events occurred in 28 (25.5%) patients (5 cardiovascular deaths and 6 cardiac transplantations) during follow up period (median 246 days, 11-888 days). When the patients with ADHF were divided by LMS according to Contal and O’Quigley's method, impaired LMS was shown to be associated with poor clinical outcome (P<0.001). Multivariate Cox regression analysis revealed that LMS was found to be an independent predictor of CV events (P=0.017) when controlled for age, gender, BMI, types of heart failure, hemoglobin, NT-proBNP and beta-blocker use. Conclusions: LMS independently predicts clinical outcome in patients with ADHF and might be used as a surrogate marker of frailty. Further studies are needed to evaluate the prognostic role of leg muscle strengthening exercise in these patients.

Clonal Involvement of the CD34+CD33− Progenitor Population by Leukemic Cells Harboring FLT3/ITD Correlates with High Risk of Relapse in Pediatric Acute Myeloid Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 227-227
Author(s):  
Jessica A. Wright ◽  
Todd A. Alonzo ◽  
Robert B. Gerbing ◽  
William G. Woods ◽  
Beverly J. Lange ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Clinical Outcome ◽  
Myeloid Leukemia ◽  
Poor Clinical Outcome ◽  
Free Survival ◽  
Allelic Ratio ◽  
Risk Of Relapse ◽  
Acute Myeloid

Abstract Internal tandem duplication of the FLT3 gene (FLT3/ITD) has been associated with high risk of relapse in acute myeloid leukemia (AML) yet nearly 25–30% of the patients with FLT3/ITD have long-term disease free survival with conventional chemotherapy. We hypothesized that FLT3/ITD AML patients with poor clinical outcome may have disease that involves less mature hematopoietic precursors than patients with favorable outcome. To test this hypothesis, we isolated less mature, CD34+CD33− and more mature, CD34+CD33+ precursor cells from 24 pediatric AML patients enrolled on Children’s Cancer Group clinical trials CCG-2891 and 2961 previously identified as having a FLT3/ITD. Granulocyte/monocyte colonies (CFU-GM) were grown in methylcellulose, harvested, and analyzed for the presence of FLT3/ITD after 14 days of growth. Twenty patients yielded sufficient cells and growth of CFU-GM colonies for analysis. FLT3/ITD was detected in CFU-GM colonies derived from CD34+CD33+ cells in all patient samples (median 80% of colonies tested per patient, range 6–100%). In contrast, FLT3/ITD was detected in CFU-GM colonies derived from CD34+/CD33− cells in only 11 of the 20 patient samples (median 46% of colonies tested per patient, range 6–100%). Of the 9 patient samples without FLT3/ITD involvement of CD34+CD33− colonies, 8 achieved a CR, 6 of whom are long-term survivors, and one patient died of non-leukemic causes. In contrast, of the 11 patients with CD34+CD33− cell involvement, 9 either failed to achieve CR or relapsed after achieving CR, and 2 died of non-leukemic causes. Actuarial progression-free survival at 4 years from diagnosis for the patients with and without FLT3/ITD in the CD34+CD33− population was 0% vs. 68% respectively (p=0.017). As allelic ratio of the FLT3/ITD has been used to define high-risk patients within the FLT3/ITD cohort, we determined the FLT3/ITD allelic ratio in our study population and correlated it with the presence of FLT3/ITD in the CD34+CD33− population. Ten of the 11 (91%) of the patient samples with FLT3/ITD involvement of the progenitor cells had high allelic ratio compared to 5 of 9 (56%) of the patients without early cell involvement. Together these data suggest that clonal dominance of FLT3/ITD containing leukemia cells at the CD34+CD33− stage of hematopoietic development is correlated with a high risk of relapse. Further studies are required to determine whether clonal dominance at this hematopoietic stage is a variable that, independent of high allelic ratio, accounts for the poor clinical outcome seen in a subset of FLT3/ITD positive AML patients.

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