Measurement of Glut-1 Expression Using Tissue Microarrays to Determine a Race Specific Prognostic Marker for Breast Cancer

2005 ◽  
Vol 93 (3) ◽  
pp. 247-253 ◽  
Author(s):  
Bodiford Lee Stackhouse ◽  
Holly Williams ◽  
Paul Berry ◽  
Greg Russell ◽  
Pamela Thompson ◽  
...  
2007 ◽  
Vol 131 (5) ◽  
pp. 767-772
Author(s):  
Jerald Luke Winter ◽  
Bodiford L. Stackhouse ◽  
Gregory B. Russell ◽  
Timothy E. Kute

Abstract Context.—African American women with breast cancer have worse prognoses than non–African Americans and might benefit with a race-specific prognostic marker such as PTEN (phosphatase and tensin homologue), a tumor suppressor protein. Reduced PTEN expression is associated with worse outcomes and resistance to trastuzumab in human epidermal growth factor receptor 2–positive breast cancers. Standardized PTEN evaluation is therefore needed. Objective.—To assess PTEN as a race-specific prognostic marker in breast cancer by using a novel semiquantitative score and a percent staining assessment. Design.—Between 1991 and 1996, 146 patients with invasive ductal adenocarcinoma were grouped by race and recurrence; there was a median follow-up of 7.2 years with 63 recurrences. Immunostaining of PTEN in tissue microarrays was correlated with race, recurrence, node positivity, stage, size, age, estrogen/progesterone receptor status, grade, and DNA ploidy. Results.—No significant racial difference was detected in mean PTEN values using either the semiquantitative score (P = .46) or the percent staining (P = .54). Unrelated to race, the percentage of tumor cells with positive PTEN expression correlated with longer time to recurrence (P = .047), positive estrogen receptor status (P = .009), and lower tumor grade (P = .005). The semiquantitative score correlated with positive estrogen receptor status (P = .01) and lower tumor grade (P = .001). Conclusions.—PTEN expression is not a race-specific biologic prognostic marker for invasive ductal adenocarcinoma. Increased PTEN expression correlates with longer time to recurrence, positive estrogen receptor status, and lower tumor grade. The novel semiquantitative score may be used to evaluate PTEN expression, but the approximate percentage of tumor cells with any PTEN staining may be the most useful measure of PTEN expression.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12552-e12552
Author(s):  
Katsuhiro Yoshikawa ◽  
Mitsuaki Ishida ◽  
Hirotsugu Yanai ◽  
Koji Tsuta ◽  
Mitsugu Sekimoto ◽  
...  

e12552 Background: Adipophilin (ADP) is a lipid-regulating protein of the perilipin/adipophilin/tail interacting protein of 47 kDa (PAT) family that coats the surfaces of cytoplasmic lipid droplets. Lipids are essential for cellular proliferation in tumor cells, and ADP, which increases the efficiency of lipid use, may contribute to cancer growth. Some previous studies suggest that ADP expression can act as a prognostic marker for specific cancers. The aim of this study is to investigate the clinicopathological significance of ADP expression in patients with triple-negative breast cancer (TNBC). Methods: Using immunohistochemical staining and tissue microarrays, we analyzed the expression profiles of ADP, glutaminase, and glutamate dehydrogenase (key enzymes in glutamine metabolism) in 61 TNBC patients who underwent operation from January 2006–December 2018. Relapse-free survival (RFS) was compared based on ADP expression and the risk factors for RFS were analyzed. Results: Fourteen (23.0%) patients were ADP-positive. As compared to ADP-negative TNBC patients, ADP-positive TNBC patients correlated with poor RFS ( p = 0.032). Among the TNBC patients with high Ki-67 labeling index, those negative for ADP exhibited better RFS than those positive for ADP ( p = 0.049). Moreover, among the patients without adjuvant chemotherapy, those negative for ADP exhibited better RFS than those positive for ADP ( p = 0.080). ADP-positive patients correlated with a significantly higher recurrence based on multivariate analyses (hazard ratio, 4.89; 95% confidence interval, 1.04–23.0; p = 0.044). Moreover, ADP expression significantly correlated with the expression of glutaminase and glutaminate dehydrogenase ( p < 0.001 and p = 0.029, respectively). Conclusions: ADP expression is a novel marker for poor prognosis of patients with TNBC and might be superior to Ki-67 as a prognostic marker. ADP expression may be related to upregulation of glutamine metabolism in cancer cells of TNBC.


Author(s):  
Amal Ramadan ◽  
Maha Hashim ◽  
Amr Abouzid ◽  
Menha Swellam

Abstract Background Aberrant DNA methylation of phosphatase and tensin homolog (PTEN) gene has been found in many cancers. The object of this study was to evaluate the clinical impact of PTEN methylation as a prognostic marker in breast cancer. The study includes 153 newly diagnosed females, and they were divided according to their clinical diagnosis into breast cancer patients (n = 112) and females with benign breast lesion (n = 41). A group of healthy individuals (n = 25) were recruited as control individuals. Breast cancer patients were categorized into early stage (0–I, n = 48) and late stage (II–III, n = 64), and graded into low grade (I–II, n = 42) and high grade (III, n = 70). Their pathological types were invasive duct carcinoma (IDC) (n = 66) and duct carcinoma in situ (DCI) (n = 46). Tumor markers (CEA and CA15.3) were detected using ELISA. DNA was taken away from the blood, and the PTEN promoter methylation level was evaluated using the EpiTect Methyl II PCR method. Results The findings revealed the superiority of PTEN methylation status as a good discriminator of the cancer group from the other two groups (benign and control) with its highest AUC and increased sensitivity (96.4%) and specificity (100%) over tumor markers (50% and 84% for CEA and 49.1% and 86.4% for CA15.3), respectively. The frequency of PTEN methylation was 96.4% of breast cancer patients and none of the benign and controls showed PTEN methylation and the means of PTEN methylation (87 ± 0.6) were significantly increased in blood samples of breast cancer group as compared to both benign and control groups (25 ± 0.7 and 12.6 ± 0.3), respectively. Methylation levels of PTEN were higher in the blood of patients with ER-positive than in patients with ER-negative cancers (P = 0.007) and in HER2 positive vs. HER2 negative tumors (P = 0.001). The Kaplan-Meier analysis recognizes PTEN methylation status as a significant forecaster of bad progression-free survival (PFS) and overall survival (OS), after 40 months follow-up. Conclusions PETN methylation could be supposed as one of the epigenetic aspects influencing the breast cancer prognosis that might foretell more aggressive actions and worse results in breast cancer patients.


2019 ◽  
Vol 121 (3) ◽  
pp. 2643-2654 ◽  
Author(s):  
Peian Cai ◽  
Zhenhui Lu ◽  
Jianjun Wu ◽  
Xiong Qin ◽  
Zetao Wang ◽  
...  

2017 ◽  
Vol 141 (10) ◽  
pp. 1402-1412 ◽  
Author(s):  
Megan L. Troxell ◽  
Thomas Long ◽  
Jason L. Hornick ◽  
Abiy B. Ambaye ◽  
Kristin C. Jensen

Context.— Immunohistochemical analysis of estrogen receptor (ER) and progesterone receptor (PgR) expression in breast cancer is the current standard of care and directly determines therapy. In 2010 the American Society of Clinical Oncology and the College of American Pathologists (ASCO/CAP) published guidelines for ER and PgR predictive testing, encompassing preanalytic, analytic, postanalytic factors; antibody validation; and proficiency testing. Objective.— To compare the performance of different antibody reagents for ER and PgR immunohistochemical analysis by using CAP proficiency testing data. Design.— The CAP PM2 survey uses tissue microarrays of ten 2-mm cores per slide. We analyzed survey data from 80 ER and 80 PgR cores by antibody clone from more than 1200 laboratories. Results.— Laboratories used the ER antibodies SP1 (72%), 6F11 (17%), 1D5 (3%), and the PgR antibodies 1E2 (61%), 16 (12%), PgR-636 (13%), PgR-1294 (8%) in 2015. While 63 of 80 ER cores (79%) were scored similarly using each of the 3 antibodies, there were significant differences for others, with SP1 yielding more positive interpretations. Four cores were scored as ER negative by more than half of the laboratories using 1D5 or 6F11, while SP1 produced positive results in more than 70% of laboratories using that antibody. Despite the greater variety of PgR antibody reagents and greater PgR tumor heterogeneity, 61 of 80 cores (76%) were scored similarly across the 4 PgR antibodies. Conclusions.— Accurate ER and PgR testing in breast cancer is crucial for appropriate treatment. The CAP proficiency testing data demonstrate differences in staining results by ER clone, with SP1 yielding more positive results.


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