Lack of MMP-9 expression is a marker for poor prognosis in Dukes’ B colorectal cancer

Background

Matrix metalloproteinases (MMPs) play a role in cancer progression by degrading extracellular matrix and basement membranes, assisting in tumour neovascularization and in supporting immune response in cancer.

Methods

We studied the prognostic value of immunohistochemical expression of MMP-2, MMP-8, and MMP-9 in a series of 619 colorectal cancer patients using tissue microarray specimens.

Results

Of the samples, 56% were positive for MMP-2, 78% for MMP-8, and 60% for MMP-9. MMP-9 associated with low WHO grade (p?<?0.001). In univariate analysis of Dukes’ B tumours, MMP-9 negativity associated with poor survival (p?=?0.018), and MMP-9 positivity was an independent prognostic marker in multivariate analysis of these tumours (p?=?0.034).

Conclusion

Negative MMP-9 expression can predict poor prognosis in Dukes’ B colorectal tumours and may prove useful for identifying patients, who should be offered adjuvant treatment.

     

Normative Reference Values of Joint Space Width Estimated by Computer-aided Joint Space Analysis (CAJSA): The Distal Interphalangeal Joint

Purpose

The study introduces reference data for a computer-aided analysis. The semiautomated computer-aided diagnostic system provides the estimation of joint space width at the distal interphalangeal joints, considering gender-specific and age-related changes.

Patients and methods

869 subjects (351 female/518 male) with hand x-rays were included and underwent measurements of joint space distances at the distal interphalangeal articulation (JSD-DIP) of the second to the fifth finger using computer-aided joint space analysis (CAJSA).

Results

Data showed a notable age-related decrease of CAJSA parameters, and an accentuated age-related joint space narrowing in women. Males showed a significantly wider JSD-DIP (+ 16.7%) compared to the female cohort for all age groups. Both men and women revealed an accentuated decrease of JSD-DIP (total) in the age group from 10 to 15 years (for men ?10.5% and for women ?17.6%). After the age of 21 years a continuous decline of the JSD-DIP (total) is observed.

Conclusion

Our data present gender-specific and age-related normative reference data for computer-aided joint space analysis, which provide a valid and reliable differentiation between disease-related joint space narrowing and age-related joint space narrowing, particularly in patients with osteoarthritis of the fingers.

     

New Strategies of ARV: the Road to Simplification

Purpose of Review

Simplification of antiretroviral therapy is a strategy aiming to reduce pill burden, drug interactions, and toxicity. This review focuses on the most recent and important studies evaluating a reduction on the number of drugs for HIV treatment, both in naive and virologically suppressed patients.

Recent Findings

Interesting studies have been performed in the past years testing dual therapy and monotherapy, with variable rates of virological control. Novel therapeutics like immunotherapy or long-acting antiretrovirals can also be considered for simplification.

Summary

Reducing the number of drugs for HIV treatment can be an option for selected patients. Current available evidence favors dual therapy over monotherapy. Future research should seek to identify the best candidates for simplification.

     

Modelling Comparative Efficacy of Drugs with Different Survival Profiles: Ipilimumab,Vemurafenib and Dacarbazine in Advanced Melanoma

Background

In the absence of head-to-head data, a common method for modelling comparative survival for cost-effectiveness analysis is estimating hazard ratios from trial publications. This assumes that the hazards of mortality are proportional between treatments and that outcomes are not polluted by subsequent therapy use. Newer techniques that compare treatments where the proportional hazards assumption is violated and adjust for use of subsequent therapies often require patient-level data, which are rarely available for all treatments.

Objective

The objective of this study was to provide a comparison of overall survival data for ipilimumab, vemurafenib and dacarbazine using data from three trials lacking a common comparator arm and confounded by the use of subsequent treatment.

Methods

We compared three estimated overall survival curves for vemurafenib and the difference compared to ipilimumab and dacarbazine. We performed a naïve comparison and adjusted it for heterogeneity between the ipilimumab and vemurafenib trials, including differences in prognostic characteristics and subsequent therapy using a published hazard function for the impact of prognostic characteristics in melanoma and trial data on the impact of second-line use of ipilimumab.

Results

The mean incremental life-years gained for patients receiving ipilimumab compared with vemurafenib were 0.34 (95 % confidence interval [CI] ?0.24 to 0.84) using the naïve comparison and 0.51 (95 % CI ?0.08 to 0.99) using the covariate-adjusted survival curve.

Conclusions

The analyses estimated the comparative efficacy of ipilimumab and vemurafenib in the absence of head-to-head patient-level data for all trials and proportional hazards in overall survival.

     

P53 nuclear stabilization is associated with <Emphasis Type="Italic">FHIT</Emphasis> loss and younger age of onset in squamous cell carcinoma of oral tongue

Background

Squamous cell carcinoma of tongue (SCCT) is expected to harbor unique clinico-pathological and molecular genetic features since a significant proportion of patients are young and exhibit no association with tobacco or alcohol.

Methods

We determined P53, epidermal growth factor receptor, microsatellite instability, human papilloma virus infection and loss of heterozygosity status at several tumor suppressor loci in one hundred and twenty one oral SCCT (SSCOT) samples and analyzed their association with clinico-pathological features and patient survival.

Results

Our results revealed a significantly higher incidence of p53 nuclear stabilization in early (as against late) onset SCCOT. FHIT loss was significantly associated with p53 nuclear stabilization and the association was stronger in patients with no history of tobacco use. Samples harboring mutation in p53 DNA binding domain or exhibiting p53 nuclear stabilization, were significantly associated with poor survival.

Conclusion

Our study has therefore identified distinct features in SCCOT tumorigenesis with respect to age and tobacco exposure and revealed possible prognostic utility of p53.

     

Trop-2 protein overexpression is an independent marker for predicting disease recurrence in endometrioid endometrial carcinoma

Background

Endometrial cancer is the most common gynecologic malignancy in developed countries. Trop-2 is a glycoprotein involved in cellular signal transduction and is differentially overexpressed relative to normal tissue in a variety of human adenocarcinomas, including endometrioid endometrial carcinomas (EEC). Trop-2 overexpression has been proposed as a marker for biologically aggressive tumor phenotypes.

Methods

Trop-2 protein expression was quantified using tissue microarrays consisting of formalin-fixed paraffin-embedded specimens from 118 patients who underwent surgical staging from 2001–9 by laparotomy for EEC. Clinicopathologic characteristics including age, stage, grade, lymphovascular space invasion, and medical comorbidities were correlated with immunostaining score. Univariate and multivariate analyses were performed for overall survival, disease-free survival, and progression-free survival in relation to clinical parameters and Trop-2 protein expression.

Results

Clinical outcome data were available for 103 patients. Strong Trop-2 immunostaining was significantly associated with higher tumor grade (p=0.02) and cervical involvement (p<0.01). Univariate analyses showed a significant association with reduced disease-free survival (DFS) (p=0.01), and a trend towards significance for overall and progression-free survival (p=0.06 and p=0.05, respectively). Multivariate analyses revealed Trop-2 overexpression and advanced FIGO stage to be independent prognostic factors for poor DFS (p=0.04 and p <0.001, respectively).

Conclusions

Trop-2 protein overexpression is significantly associated with higher tumor grade and serves as an independent prognostic factor for DFS in endometrioid endometrial cancer.

     

FGFR1 expression defines clinically distinct subtypes in pancreatic cancer

Background

The clinical significance of fibroblast growth factor receptor 1 (FGFR1) protein expression in pancreatic cancer is largely unknown. In this study, we aimed investigate the clinical significance of FGFR1 expression in pancreatic cancer.

Methods

First, we investigated the relationship between FGFR pathway gene expression and clinicopathological data in three pancreatic cancer cohorts containing 313 cases. Subsequently, to confirm the findings from the discovery cohorts, we performed immunohistochemistry (IHC) of FGFR1 protein in a validation cohort of 205 pancreatic cancer cases.

Results

In discovery cohort 1, FGFR1 and Klotho beta (KLB) overexpression was associated with low tumor stage (P?<?0.05), low tumor grade (P?<?0.05), and better overall survival. Multivariate analysis predicted FGFR1 (P?<?0.05) as a prognostic factor for better overall survival. In discovery cohorts 2 and 3, only FGFR1 overexpression was associated with better overall survival (P?<?0.05). In the validation cohort, there were 15.7% and 61% strong and weak/moderate FGFR1-positive cases, respectively. FGFR1-positive cases showed better overall survival than FGFR1-negative cases (P?<?0.05). Furthermore, multivariate analysis revealed FGFR1 positivity as an independent prognostic factor for better overall survival in pancreatic cancer patients (hazard ratio 0.677, 95% confidence interval 0.471–0.972, P?=?0.035).

Conclusions

FGFR1 expression, as estimated by IHC, may be used to define clinically distinct subtypes in pancreatic cancer. Moreover, FGFR1-based subclassification of pancreatic cancer may lead to new therapeutic approaches for the FGFR1-positive subtype.

     

Membranous CD24 expression as detected by the monoclonal antibody SWA11 is a prognostic marker in non-small cell lung cancer patients

Background

Lung cancer is one of the most common malignant neoplasms worldwide and has a high mortality rate. To enable individualized therapy regimens, a better understanding of the molecular tumor biology has still to be elucidated. The expression of the cell surface protein CD24 has already been claimed to be associated with shorter patient survival in non-small cell lung cancer (NSCLC), however, the prognostic value and applicability of CD24 immunostaining in paraffin embedded tissue specimens has been questioned due to the recent acknowledgement of restricted epitope specificity of the commonly used antibody SN3b.

Methods

A cohort of 137 primary NSCLC cases was immunostained with a novel CD24 antibody (clone SWA11), which specifically recognizes the CD24 protein core and the resulting expression data were compared with expression profiles based on the monoclonal antibody SN3b. Furthermore, expression data were correlated to clinico-pathological parameters. Univariate and multivariate survival analyses were conducted with Kaplan Meier estimates and Cox regression, respectively.

Results

CD24 positivity was found in 34 % resp. 21 % (SN3b) of NSCLC with a membranous and/or cytoplasmic staining pattern. Kaplan-Meier analyses revealed that membranous, but not cytoplasmic CD24 expression (clone SWA11) was associated with lympho-nodular spread and shorter overall survival times (both p?<?0.05). CD24 expression established by SN3b antibodies did not reveal significant clinicopathological correlations with overall survival, neither for cytoplasmic nor membranous CD24 staining.

Conclusions

Membranous CD24 immunoreactivity, as detected with antibody clone SWA11 may serve as a prognostic factor for lymphonodular spread and poorer overall survival. Furthermore, these results corroborate the importance of a careful distinction between membranous and cytoplasmic localisation, if CD24 is to be considered as a potential prognostic biomarker.

     

Prognostic value of the MicroRNA regulators Dicer and Drosha in non-small-cell lung cancer: co-expression of Drosha and miR-126 predicts poor survival

Background

Dicer and Drosha are important enzymes for processing microRNAs. Recent studies have exhibited possible links between expression of different miRNAs, levels of miRNA processing enzymes, and cancer prognosis. We have investigated the prognostic impact of Dicer and Drosha and their correlation with miR-126 expression in a large cohort of non-small cell lung cancer (NSCLC) patients. We aimed to find patient groups within the cohort that might have an advantage of receiving adjunctive therapies.

Methods

Dicer expression in the cytoplasm and Drosha expression in the nucleus were evaluated by manual immunohistochemistry of tissue microarrays (TMAs), including tumor tissue samples from 335 patients with resected stages I to IIIA NSCLC. In addition, in situ hybridizations of TMAs for visualization of miR-126 were performed. Kaplan–Meier analysis was performed, and the log-rank test via SPSS v.22 was used for estimating significance levels.

Results

In patients with normal performance status (ECOG?=?0, n?=?197), high Dicer expression entailed a significantly better prognosis than low Dicer expression (P?=?0.024). Dicer had no significant prognostic value in patients with reduced performance status (ECOG?=?1–2, n?=?138). High Drosha expression was significantly correlated with high levels of the microRNA 126 (miR-126) (P?=?0.004). Drosha/miR-126 co-expression had a significant negative impact on the disease-specific survival (DSS) rate (P?<?0.001). Multivariate analyses revealed that the interaction Dicer*Histology (P?=?0.049) and Drosha/miR-126 co-expression (P?=?0.033) were independent prognostic factors.

Conclusions

In NSCLC patients with normal performance status, Dicer is a positive prognostic factor. The importance of Drosha as a prognostic factor in our material seems to be related to miR-126 and possibly other microRNAs.

     

<Emphasis Type="Italic">Helicobacter bilis</Emphasis>-Associated Suppurative Cholangitis in a Patient with X-Linked Agammaglobulinemia

?

Helicobacter bilis is a commensal bacterium causing chronic hepatitis and colitis in mice. In humans, enterohepatic Helicobacter spp. are associated with chronic hepatobiliary diseases.

Purpose

We aimed at understanding the microbial etiology in a patient with X-linked agammaglobulinemia presenting with suppurative cholangitis.

Methods

16S rDNA PCR directly performed on a liver biopsy retrieved DNA of H. bilis.

Results

Clinical outcome resulted in the normalization of clinical and biological parameters under antibiotic treatment by a combination of ceftriaxone, metronidazole, and doxycyclin followed by a 2-week treatment with moxifloxacin and a 2-month treatment with azithromycin.

Conclusion

In conclusion, these data suggest a specific clinical and microbiological approach in patients with humoral deficiency in order to detect H. bilis hepatobiliary diseases.

     

Glücklich als Paar – glücklicher Schlaf?

Background

Millions of people share a bed with their partner. Sleep und relationship could possibly influence each other.

Objectives

To identify and discuss connections between relationship and sleep quality.

Methods

Review of the literature in electronic databases.

Results

Conflict and violence in relationships lead to decreases in both partners’ sleep quality. Constructive approaches to resolving conflicts is necessary for good sleep, and vice versa. Women prefer partners with sleep-wake rhythms matching their own and report higher relationship satisfactions when the couple’s chronotypes are compatible.

Conclusions

Sleep and circadian rhythms play important roles in relationships. When treating insomnia, the relationship and the partner’s sleep should be taken into account.

     

EphA4 is a prognostic factor in gastric cancer

Background

Erythropoietin-producing hepatocellular (Eph) receptor, consisting of a family of receptor tyrosine kinases, plays critical roles in tumour development and is considered an attractive target for cancer therapy.

Methods

Tumour samples were obtained from 222 patients with gastric adenocarcinoma who underwent gastrectomy. The expressions of EphA2, EphA4, and ephrinA1 were evaluated immunohistochemically.

Results

High expressions of EphA2, EphA4, and ephrinA1 significantly correlated with variables related to tumour progression, including the depth of invasion, metastatic lymph nodes, pathological stage, and distant metastasis or recurrent disease. High expressions of EphA2, EphA4, and ephrinA1 were significantly associated with poorer disease-specific survival (DSS; p?<?0.001, p?<?0.001, p?=?0.026). On multivariate analysis, EphA4 was an independent prognostic factor of DSS (hazard ratio [HR], 2.3; 95% confidence interval [CI], 1.1-4.8; p?=?0.028), and EphA2 tended to be a prognostic factor (HR, 2.4; 95% CI, 1.0-5.8; p?=?0.050). In stage II and III cancer, EphA4 and EphA2 were both significantly associated with shorter survival (p?=?0.007 and 0.019), but only EphA2 was an independent prognostic factor (HR, 2.6; 95% CI, 1.1-6.3; p?=?0.039).

Conclusion

EphA4 may play important roles in tumor progression and outcomes in patients with gastric cancer.

     

Ethical Assessment of Human Embryonic Stem Cell Research According to Turkish Muslim Scholars: First Critical Analysis and Some Reflections

Background

Turkey, with a Muslim population of officially over 99 %, is one of the few secular states in the Muslim world. Although state institutions are not based on Islamic juridical and ethical norms, the latter play a significant role in defining people’s attitudes towards controversial issues in the modern world, especially when backed by opinions of Muslim scholars living in Turkey. Accordingly, opinions of Muslim scholars undoubtedly have an important effect on bioethical decisions made by institutions and individuals.

Objective(s)

To explore the ethical positions of Muslim scholars living in Turkey and their arguments used in the ethical assessment of embryonic stem cell research; to discuss the biological-moral tensions arising in medical research on human embryos.

Design

Qualitative study.

Setting

Muslim scholars located in different parts of Turkey.

Methods

Qualitative method, involving the collection of opinions of various scholars, by means of 15 individual semi-structured interviews, evaluated using thematic qualitative analysis.

Results

Positions regarding embryonic stem cell research differ among Muslim scholars in Turkey. On the other hand, even where positions are similar, they are often supported by different arguments.

Conclusion

Despite the heterogeneity of the arguments presented, the dominant position considers embryonic stem cell research as morally acceptable.

     

Use of predicted vital status to improve survival analysis of multidrug-resistant tuberculosis cohorts

Background

Multidrug-resistant tuberculosis (MDR-TB) cohorts often lack long-term survival data, and are summarized instead by initial treatment outcomes. When using Cox proportional hazards models to analyze these cohorts, this leads to censoring subjects at the time of the initial treatment outcome, instead of them providing full survival data. This may violate the non-informative censoring assumption of the model and may produce biased effect estimates. To address this problem, we develop a tool to predict vital status at the end of a cohort period using the initial treatment outcome and assess its ability to reduce bias in treatment effect estimates.

Methods

We derive and apply a logistic regression model to predict vital status at the end of the cohort period and modify the unobserved survival outcomes to better match the predicted survival experience of study subjects. We compare hazard ratio estimates for effect of an aggressive treatment regimen from Cox proportional hazards models using time to initial treatment outcome, predicted vital status, and true vital status at the end of the cohort period.

Results

Models fit from initial treatment outcomes underestimate treatment effects by up to 22.1%, while using predicted vital status reduced this bias by 5.4%. Models utilizing the predicted vital status produce effect estimates consistently stronger and closer to the true treatment effect than estimates produced by models using the initial treatment outcome.

Conclusions

Although studies often use initial treatment outcomes to estimate treatment effects, this may violate the non-informative censoring assumption of the Cox proportional hazards model and result in biased treatment effect estimates. Using predicted vital status at the end of the cohort period may reduce this bias in the analyses of MDR-TB treatment cohorts, yielding more accurate, and likely larger, treatment effect estimates. Further, these larger effect sizes can have downstream impacts on future study design by increasing power and reducing sample size needs.

     

Multiple Score Comparison: a network meta-analysis approach to comparison and external validation of prognostic scores

Background

Prediction models and prognostic scores have been increasingly popular in both clinical practice and clinical research settings, for example to aid in risk-based decision making or control for confounding. In many medical fields, a large number of prognostic scores are available, but practitioners may find it difficult to choose between them due to lack of external validation as well as lack of comparisons between them.

Methods

Borrowing methodology from network meta-analysis, we describe an approach to Multiple Score Comparison meta-analysis (MSC) which permits concurrent external validation and comparisons of prognostic scores using individual patient data (IPD) arising from a large-scale international collaboration. We describe the challenges in adapting network meta-analysis to the MSC setting, for instance the need to explicitly include correlations between the scores on a cohort level, and how to deal with many multi-score studies. We propose first using IPD to make cohort-level aggregate discrimination or calibration scores, comparing all to a common comparator. Then, standard network meta-analysis techniques can be applied, taking care to consider correlation structures in cohorts with multiple scores. Transitivity, consistency and heterogeneity are also examined.

Results

We provide a clinical application, comparing prognostic scores for 3-year mortality in patients with chronic obstructive pulmonary disease using data from a large-scale collaborative initiative. We focus on the discriminative properties of the prognostic scores. Our results show clear differences in performance, with ADO and eBODE showing higher discrimination with respect to mortality than other considered scores. The assumptions of transitivity and local and global consistency were not violated. Heterogeneity was small.

Conclusions

We applied a network meta-analytic methodology to externally validate and concurrently compare the prognostic properties of clinical scores. Our large-scale external validation indicates that the scores with the best discriminative properties to predict 3 year mortality in patients with COPD are ADO and eBODE.

     

Picture perfect—how seeking perfection influences sleep and romantic relationships

Background

Studies have shown that sleep quality is negatively affected by perfectionism. Moreover, partner- or relationship-oriented perfectionism negatively influences relationship quality.

Objective

This paper aims to investigate the association of general perfectionism with sleep quality and relationship quality.

Materials and methods

A study assessing perfectionism, sleep quality, and relationship quality was performed via analyzing online questionnaires completed by 489 German adults from the general population.

Results

Participants with impaired sleep showed a higher level of maladaptive perfectionism (concern over mistakes and doubts, parental expectations, and criticism) than participants with good sleep, whereby the severity of sleep problems was not determining. Relationship quality is affected by perfectionism. However, this association is mediated by sleep quality.

Conclusion

Perfectionism is associated with worse sleep quality but not with worse relationship quality when sleep quality is integrated into the model as a mediator.

     

Micronized palmitoylethanolamide reduces joint pain and glial cell activation

Objective and design

Temporomandibular disorder (TMD) is a common painful condition in the temporomandibular joint (TMJ). Joint inflammation is believed to be a chief cause of pain in patients with TMD, through the release of pro-inflammatory cytokines that induce peripheral sensitization of nerve terminals followed by microglial stimulation.

Materials and subject

TMJ was induced in rats with the injection of complete Freund’s adjuvant (CFA) emulsion into the left TMJ capsule.

Treatment

The present study would assess the effects of micronized palmitoylethanolamide (m-PEA) on glial activation and trigeminal hypersensitivity.

Methods

Ten mg/kg m-PEA or corresponding vehicle was administered 1 h after CFA and mechanical allodynia and edema were evaluated at 24 and 72 h after CFA injection.

Results

CFA-injected animals showed TMJ edema and ipsilateral mechanical allodynia accompanied by a robust growth in GFAP protein-positive satellite glial cells and activation of resident macrophages in the TG. Moreover, m-PEA administration significantly reduced the degree of TMJ damage and pain, macrophage activation in TG and up-regulation of Iba1.

Conclusions

The results confirm that m-PEA could represent a novel approach for monitoring pain during trigeminal nerve sensitization.

     

Expression of podocalyxin-like protein is an independent prognostic biomarker in resected esophageal and gastric adenocarcinoma

Background

Podocalyxin-like protein (PODXL) is a cell surface transmembrane glycoprotein, the expression of which has been associated with poor prognosis in a range of malignancies. The aim of this study was to investigate the impact of PODXL expression on survival in esophageal and gastric adenocarcinoma.

Methods

The study cohort consists of a consecutive series of 174 patients with esophageal (including the gastroesophageal junction) or gastric adenocarcinoma, surgically treated between 2006 and 2010 and not subjected to neoadjuvant treatment. Immunohistochemical expression of PODXL was assessed in tissue microarrays with cores from primary tumors, lymph node metastases, intestinal metaplasia and adjacent normal epithelium. Survival analyses were performed on patients with no distant metastases and no macroscopic residual tumor.

Results

In the majority of cases, expression of PODXL was significantly higher in cancer cells compared to normal epithelial cells and was significantly associated with lymph node metastases and high grade tumors. In esophageal adenocarcinoma, Kaplan-Meier analyses revealed that patients with PODXL negative tumors had a superior time to recurrence (TTR) and overall survival (OS) compared to patients with PODXL positive tumors. In gastric adenocarcinoma, patients with PODXL negative tumors had a superior TTR and a trend towards an improved OS. In esophageal and gastric adenocarcinoma combined, the prognostic significance of PODXL expression on TTR was confirmed in unadjusted Cox regression analysis (HR?=?5.36, 95 % CI 1.68-17.06, p?=?0.005) and remained significant in the adjusted model (HR?=?3.39, 95 % CI 1.01-11.35, p?=?0.048). Moreover, the impact of PODXL expression on OS was also confirmed in unadjusted analysis (HR?=?2.52, 95 % CI 1.31-4.85, p?=?0.006) and remained significant in the adjusted model (HR?=?2.03, 95 % CI 1.04-3.98, p?=?0.039).

Conclusions

In esophageal and gastric adenocarcinoma, PODXL expression is an independent prognostic biomarker for reduced time to recurrence and poor overall survival. This is the first report on the prognostic role of PODXL in esophageal adenocarcinoma and validates recent findings in gastric cancer.

     

Deficiencies in elements involved in TLR4-receptor signalling in RBL-2H3 cells

Objective

RBL-2H3 cells express Toll-like receptors, including TLR4. This study aims to assess various aspects of the TLR4 pathway.

Methods

RBL-2H3 cells were indirectly stained for cell surface TLR4, 25 CD14 and intracellular MyD88 proteins and analysed through flow cytometry for single-colour staining.

Results

While TLR4-receptors are expressed in RBL-2H3 cells, associated elements involved in the signaling pathway, CD14 and MyD88, are not.

Conclusion

Care should be taken if RBL-2H3 cells are used to study aspects of the innate immune system in mast cells.

     

Expression of a-Tocopherol-Associated protein (TAP) is associated with clinical outcome in breast cancer patients

Background

The role of vitamin E in breast cancer prevention and treatment has been widely investigated, and the different tocopherols that comprise this nutrient have been shown to have divergent associations with cancer outcome. Our previous studies have shown that α-Tocopherol-associated protein (TAP), a vitamin E binding protein, may function as a tumor suppressor-like factor in breast carcinogenesis. The current study addresses the association of TAP expression with breast cancer clinical outcomes.

Methods

Immunohistochemical stain for TAP was applied to a tissue microarray from a breast cancer cohort consisting of 271 patients with a median follow-up time of 5.2 years. The expression of TAP in tumor cells was compared with patient’s clinical outcome at 5 years after diagnosis. The potential role of TAP in predicting outcome was also assessed in clinically relevant subsets of the cohort. In addition, we compared TAP expression and Oncotype DX scores in an independent breast cancer cohort consisting of 71 cases.

Results

We demonstrate that the expression of TAP was differentially expressed within the breast cancer cohort, and that ER+/PR?±?tumors were more likely to exhibit TAP expression. TAP expression was associated with an overall lower recurrence rate and a better 5-year survival rate. This association was primarily in patients with ER+ tumors; exploratory analysis showed that this association was strongest in patients with node-positive tumors and was independent of stage and treatment with chemotherapy. TAP expression in ER/PR negative or triple negative tumors had no association with clinical outcome. In addition, we did not observe an association between TAP expression and Oncotype DX recurrence score.

Conclusions

The significant positive association we found for α-Tocopherol-associated protein with outcome in breast cancer may help to better define and explain studies addressing α-tocopherol’s association with cancer risk and outcome. Additionally, further studies to validate and extend these findings may allow TAP to serve as a breast-specific prognostic marker in breast cancer patients, especially in those patients with ER+ tumors.