Nizar K. Wehbi

Quantitative Fluorescence Imaging Analysis for Cancer Biomarker Discovery: Application to β-Catenin in Archived Prostate Specimens

The surprising disparity between the number of protein-encoding genes (∼30,000) in the human genome and the number of proteins (∼300,000) in the human proteome has inspired the development of translational proteomics aimed at protein expression profiling of disease states. Translational proteomics, which offers the promise of early disease detection and individualized therapy, requires new methods for the analysis of clinical specimens. We have developed quantitative flourescence imaging analysis (QFIA) for accurate, reproducible quantification of proteins in slide-mounted tissues. The method has been validated for the analysis of β-catenin in archived prostate specimens fixed in formalin. QFIA takes advantage of the linearity of fluorescence antibody signaling for tissue epitope content, a feature validated for β-catenin in methacarn-fixed prostate specimens analyzed by reverse-phase protein array analysis and QFIA (r = 0.97). QFIA of β-catenin in formaldehyde-fixed tissues correlated directly with β-catenin content (r = 0.86). Application of QFIA in a cross-sectional study of biopsies from 42 prostate cancer (PC) cases and 42 matched controls identified β-catenin as a potential field marker for PC. Receiver operating characteristic plots revealed that β-catenin expression in the normal-appearing acini of cancerous glands identified 42% (95% confidence intervals, 26-57%) of cancer cases, with 88% (95% confidence intervals, 80-96%) specificity. The marker may contribute to a PC biomarker panel. In conclusion, we report the development and validation of a new method for fluorescence quantification of proteins in archived tissues and its application to archived specimens for an evaluation of β-catenin expression as a biomarker for PC. (Cancer Epidemiol Biomarkers Prev 2007;16(7):1371–81)

Pan-cadherin as a high level phenotypic biomarker for prostate cancer.

PURPOSE High level phenotypic biomarkers such as cadherins are needed to identify individuals at risk for biologically active prostate cancer and determine which individuals with elevated prostate specific antigen or a prostate nodule are candidates for re-biopsy. Cadherins are a high level phenotypic biomarker associated with decreased cell adhesion, which is a cardinal event in carcinogenesis. Recently we reported that G-actin and tissue transglutaminase type II are potential biomarkers for prostate cancer. In this study we present cadherins as a potential third component of the biomarker profile. MATERIALS AND METHODS Prostate tissues from 38 patients with cancer and 33 controls with a 10-year prostate cancer-free followup were labeled for pan-cadherin by immunohistochemical testing. Immunoreactivity was quantified using a Pathology Workstation (Autocyte Inc., Elon College, North Carolina). RESULTS Visually benign glands from controls generally expressed cadherins, whereas regions of adenocarcinoma were generally negative. On quantitative immunohistochemistry 36 of 38 prostate cancer cases expressed a lower mean percent area positive for cadherin than the 19 benign prostatic hyperplasia and 14 prostatitis cases (odds ratio 978, 95% confidence interval 45 to 21,140, relative risk 18, 95% confidence interval 5 to 67, p <0.0001). Receiver operating characteristics analysis of immunohistochemical testing data showed that an optimal threshold of 7 produced 95% sensitivity and 100% specificity. CONCLUSIONS Quantitative down-regulation of cadherin expression in prostate cancer tissue sections is a strong biomarker for prostate cancer. Analysis of cadherin and other high level phenotypic biomarker expression in the premalignant field may provide additional diagnostic information to decide which patients need re-biopsy, more intensive monitoring or chemoprevention.

The joint relationship between organizational design factors and Hr practice factors on direct care workers’ job satisfaction and turnover intent

Background: Human resource (HR) practices, such as training and communication, have been linked to positive employee job commitment and lower turnover intent for direct care workers (DCWs). Not many studies have looked at the combined interaction of HR practices and organizational structure. Purpose: The aim of this study is to examine the relationship between organizational structure (centralization, formalization, and span of control) and HR practices (training, horizontal communication, and vertical communication) on DCW’s job satisfaction and turnover intent. Methodology: Data were collected from 58 long-term care facilities in five states. We used latent class analysis to group facility characteristics into three sets of combinations: “organic,” “mechanistic,” and “minimalist.” We used multivariate regression to test the relationship of each of these groups on DCW’s job satisfaction and turnover intent. Findings: After controlling for state, organizational, and individual covariates, the organic group, which represents decentralized and less formalized structures and high levels of job training and communication, was positively related to job satisfaction and negatively related to intent to leave. On the other hand, the minimalist group, which is characterized by low levels of job-related training and communication, showed no significant differences from the mechanistic group (referent) on job satisfaction and intent to leave. Practice Implications: These findings imply that managers in long-term care facilities may want to consider adopting organic, decentralized structures and HR practices to retain DCWs.

Epidemiologic and Clinical Profiles of Breast Diseases in Niger

This study aimed at characterizing epidemiologic and clinical profiles of breast diseases in Niger during the period of 2010–2013 at the National Hospital of Niamey. Medical records were abstracted for demographic, reproductive, clinical, and treatment information. A process map of patient navigation and barriers to seeking medical care was developed after interviewing 26 local health professionals who encounter and/or manage breast diseases. We identified 245 breast cancers and 122 other breast diseases. Mean age of breast cancer patients was 45.4 (±13.26 years) and that of breast diseases was 31(±12.5 years) with 1/3 of cancers under age 44. Infection-related diseases represented 24% of non-cancers. Male breast diseases represented 4.75% of diseases and 2.05% of cancers. Only 37.1% of cancers had histopathologic confirmation and 90% of cancer patients presented at advanced stages and mastectomy was performed for 66% of breast cancers. Patient and system barriers to care were common in diagnosing and treating breast diseases. Women in Niger have double burden of infectious breast diseases and emerging breast cancer. Younger age and late diagnosis are common features. Reducing barriers to access to care, down-staging of cancer, implementation of clinical guidelines for managing advanced cases are important needs for reducing breast cancer morbidity and mortality in Niger.

Longitudinal associations between body mass index, physical activity, and healthy dietary behaviors in adults: A parallel latent growth curve modeling approach

Background Physical activity (PA) and healthy dietary behaviors (HDB) are two well-documented lifestyle factors influencing body mass index (BMI). This study examined 7-year longitudinal associations between changes in PA, HDB, and BMI among adults using a parallel latent growth curve modeling (LGCM). Methods We used prospective cohort data collected by a private company (SimplyWell LLC, Omaha, NE, USA) implementing a workplace health screening program. Data from a total of 2,579 adults who provided valid BMI, PA, and HDB information for at least 5 out of 7 follow-up years from the time they entered the program were analyzed. PA and HDB were subjectively measured during an annual online health survey. Height and weight measured during an annual onsite health screening were used to calculate BMI (kg·m2). The parallel LGCMs stratified by gender and baseline weight status (normal: BMI<25, overweight BMI 25–29.9, and obese: BMI>30) were fitted to examine the longitudinal associations of changes in PA and HDB with change in BMI over years. Results On average, BMI gradually increased over years, at rates ranging from 0.06 to 0.20 kg·m2·year, with larger increases observed among those of normal baseline weight status across genders. The increases in PA and HDB were independently associated with a smaller increase in BMI for obese males (b = -1.70 and -1.98, respectively), and overweight females (b = -1.85 and -2.46, respectively) and obese females (b = -2.78 and -3.08, respectively). However, no significant associations of baseline PA and HDB with changes in BMI were observed. Conclusions Our study suggests that gradual increases in PA and HDB are independently associated with smaller increases in BMI in overweight and obese adults, but not in normal weight individuals. Further study is warranted to address factors that check increases in BMI in normal weight adults.

1717: Quantitative Fluorescence Imaging Analysis for Cancer Biomarker Discovery: Application to B-Catenin in Archived Prostate Specimens

The surprising disparity between the number of protein-encoding genes ( approximately 30,000) in the human genome and the number of proteins ( approximately 300,000) in the human proteome has inspired the development of translational proteomics aimed at protein expression profiling of disease states. Translational proteomics, which offers the promise of early disease detection and individualized therapy, requires new methods for the analysis of clinical specimens. We have developed quantitative fluorescence imaging analysis (QFIA) for accurate, reproducible quantification of proteins in slide-mounted tissues. The method has been validated for the analysis of beta-catenin in archived prostate specimens fixed in formalin. QFIA takes advantage of the linearity of fluorescence antibody signaling for tissue epitope content, a feature validated for beta-catenin in methacarn-fixed prostate specimens analyzed by reverse-phase protein array analysis and QFIA (r = 0.97). QFIA of beta-catenin in formaldehyde-fixed tissues correlated directly with beta-catenin content (r = 0.86). Application of QFIA in a cross-sectional study of biopsies from 42 prostate cancer (PC) cases and 42 matched controls identified beta-catenin as a potential field marker for PC. Receiver operating characteristic plots revealed that beta-catenin expression in the normal-appearing acini of cancerous glands identified 42% (95% confidence intervals, 26-57%) of cancer cases, with 88% (95% confidence intervals, 80-96%) specificity. The marker may contribute to a PC biomarker panel. In conclusion, we report the development and validation of a new method for fluorescence quantification of proteins in archived tissues and its application to archived specimens for an evaluation of beta-catenin expression as a biomarker for PC.