Immunohistochemical analysis of Bin1/Amphiphysin II in human tissues: Diverse sites of nuclear expression and losses in prostate cancer

2003 ◽  
Vol 88 (3) ◽  
pp. 635-642 ◽  
Author(s):  
James B. DuHadaway ◽  
Frank J. Lynch ◽  
Shawn Brisbay ◽  
Carlos Bueso-Ramos ◽  
Patricia Troncoso ◽  
...  
2020 ◽  
Author(s):  
Azadeh khalvandi ◽  
Maryam Abolhasani ◽  
Zahra Madjd ◽  
Mehdi Shekarabi ◽  
Masoumeh Kourosh Arami ◽  
...  

Abstract Melanoma antigen gene A3 (MAGE-A3) is one of the most immunogenic cancer- testis antigens and is common in various types of cancers. Due to its high immunogenicity and oncogenicity, it has been a candidate for cancer immunotherapy and used as a cancer vaccine in clinical trials of various types of cancers. In this study, for the first time, we performed immunohistochemical analysis to evaluate the expression of MAGE-A3 in 153 formalin-fixed paraffin-embedded prostate tissue samples including 112 cases of prostate cancer (PCa), 22 cases of benign prostatic hyperplasia (BPH) and 19 cases of high-grade prostatic intraepithelial neoplasia (HPIN). Both nuclear and cytoplasmic expressions of MAGE-A3 with different staining intensities were observed among the tissues. Increased expression of MAGE-A3 was significantly found in PCa tissues compared to both HPIN and BPH tissues (nuclear expression at P = 0.011, and cytoplasmic expression at p = 0.034; for both comparisons P < 0.0001, respectively). A significant correlation was observed between higher nuclear and cytoplasmic expressions of MAGE-A3 with Gleason score (P < 0.0001 and 0.006, respectively). Increased expression of MAGE-A3 was associated with shorter biochemical recurrence-free survival (BCR-FS) and disease-free survival (DFS) of patients (P = 0.042 and P = 0.0001, respectively). In multivariate analysis, nuclear expression of MAGE-A3 and Gleason score (≤ 7 vs > 7) were independent predictors of the DFS (both; P = 0.019). Nuclear expression of MAGE-A3 was also significantly related to BCR-FS (P = 0.015). MAGE-A3 can be considered as a valuable predictor for poor prognosis and an attractive option for vaccine immunotherapy in patients with PCa.


2020 ◽  
Author(s):  
Lungwani Muungo

The androgen receptor (AR) plays a critical role in the development and the progression of prostate cancer. Alterations in theexpression of AR coregulators lead to AR hypersensitivity, which is one of the mechanisms underlying the progression ofprostate cancer into a castrate-resistant state. Octamer transcription factor 1 (Oct1) is a ubiquitous member of the POUhomeodomainfamily that functions as a coregulator of AR. In our study, the contribution of Oct1 to prostate cancerdevelopment was examined. Immunocytochemistry analysis showed that Oct1 is expressed in the nuclei of LNCaP cells.siRNA-mediated silencing of Oct1 expression inhibited LNCaP cell proliferation. Immunohistochemical analysis of Oct1expression in tumor specimens obtained from 102 patients with prostate cancer showed a positive correlation of Oct1immunoreactivity with a high Gleason score and AR immunoreactivity (p 5 0.0042 and p &lt; 0.0001, respectively). Moreover,patients with high immunoreactivity of Oct1 showed a low cancer-specific survival rate, and those patients with highimmunoreactivities of both Oct1 and AR exhibited poorer cancer-specific prognosis. Multivariate hazard analysis revealed asignificant correlation between high Oct1 immunoreactivity and poor cancer-specific survival (p 5 0.012). These resultsdemonstrate that Oct1 can be a prognostic factor in prostate cancer as a coregulator of AR and may lead to the developmentof a new therapeutic intervention for prostate cancer.


Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3608
Author(s):  
Liliana Rounds ◽  
Ray B. Nagle ◽  
Andrea Muranyi ◽  
Jana Jandova ◽  
Scott Gill ◽  
...  

Glyoxalase 1 (GLO1) is an enzyme involved in the detoxification of methylglyoxal (MG), a reactive oncometabolite formed in the context of energy metabolism as a result of high glycolytic flux. Prior clinical evidence has documented GLO1 upregulation in various tumor types including prostate cancer (PCa). However, GLO1 expression has not been explored in the context of PCa progression with a focus on high-grade prostatic intraepithelial neoplasia (HGPIN), a frequent precursor to invasive cancer. Here, we have evaluated GLO1 expression by immunohistochemistry in archival tumor samples from 187 PCa patients (stage 2 and 3). Immunohistochemical analysis revealed GLO1 upregulation during tumor progression, observable in HGPIN and PCa versus normal prostatic tissue. GLO1 upregulation was identified as a novel hallmark of HGPIN lesions, displaying the highest staining intensity in all clinical patient specimens. GLO1 expression correlated with intermediate–high risk Gleason grade but not with patient age, biochemical recurrence, or pathological stage. Our data identify upregulated GLO1 expression as a molecular hallmark of HGPIN lesions detectable by immunohistochemical analysis. Since current pathological assessment of HGPIN status solely depends on morphological features, GLO1 may serve as a novel diagnostic marker that identifies this precancerous lesion.


The Prostate ◽  
2021 ◽  
Author(s):  
Giuseppe Broggi ◽  
Arturo Lo Giudice ◽  
Marina Di Mauro ◽  
Maria Giovanna Asmundo ◽  
Elisabetta Pricoco ◽  
...  

2015 ◽  
Vol 22 (4) ◽  
pp. 519-530 ◽  
Author(s):  
Rodrigo B de Alexandre ◽  
Anelia D Horvath ◽  
Eva Szarek ◽  
Allison D Manning ◽  
Leticia F Leal ◽  
...  

We hypothesized that mutations that inactivate phosphodiesterase (PDE) activity and lead to increased cAMP and cyclic guanosine monophosphate levels may be associated with prostate cancer (PCa). We sequenced the entire PDE coding sequences in the DNA of 16 biopsy samples from PCa patients. Novel mutations were confirmed in the somatic or germline state by Sanger sequencing. Data were then compared to the 1000 Genome Project. PDE, CREB and pCREB protein expression was also studied in all samples, in both normal and abnormal tissue, by immunofluorescence. We identified three previously described PDE sequence variants that were significantly more frequent in PCa. Four novel sequence variations, one each in thePDE4B,PDE6C,PDE7BandPDE10Agenes, respectively, were also found in the PCa samples. Interestingly,PDE10AandPDE4Bnovel variants that were present in 19 and 6% of the patients were found in the tumor tissue only. In patients carrying PDE defects, there was pCREB accumulation (P<0.001), and an increase of the pCREB:CREB ratio (patients 0.97±0.03; controls 0.52±0.03;P-value <0.001) by immunohistochemical analysis. We conclude that PDE sequence variants may play a role in the predisposition and/or progression to PCa at the germline and/or somatic state respectively.


Author(s):  
Davide Vecchiotti ◽  
Daniela Verzella ◽  
Daria Capece ◽  
Jessica Cornice ◽  
Mauro Di Vito Nolfi ◽  
...  

2001 ◽  
Vol 171 (1) ◽  
pp. R1-R4 ◽  
Author(s):  
SK Peirce ◽  
WY Chen ◽  
WY Chen

Human prolactin (hPRL) has been reported to be involved in breast and prostate cancer development. The hPRL receptor (hPRLR) is expressed in a wide variety of tissues in at least three isoforms. In this study, a one-step real time reverse transcription PCR technique was used to determine relative expression levels of hPRLR mRNA in eleven human breast cancer cell lines, HeLa cells, three prostate cancer cell lines and nine normal human tissues. The housekeeping gene beta-actin was used for internal normalization. We demonstrate that hPRLR mRNA is up-regulated in six of the eleven breast cancer cell lines tested when compared with normal breast tissue. Of the cancer cell lines tested, we found that T-47D cells have the highest level of hPRLR mRNA, followed by MDA-MB-134, BT-483, BT-474, MCF-7 and MDA-MB-453 cells. In two breast cancer cell lines (MDA-MB-468 and BT-549), the hPRLR levels were found to be comparable to that of normal breast tissue. Three breast cancer cell lines (MDA-MB-436, MDA-MB-157 and MDA-MB-231) expressed hPRLR mRNA at levels lower than that of normal tissue. In contrast, in all three commonly used prostate cancer cell lines (LNCaP, PC-3 and DU 145), the levels of hPRLR mRNA were found to be down-regulated relative to that of normal prostate tissue. Of nine normal human tissues tested, we found that the uterus and the breast have the highest levels of hPRLR mRNA, followed by the kidney, the liver, the prostate and the ovary. The levels of hPRLR mRNA were the lowest among the trachea, the brain and the lung.


2001 ◽  
Vol 92 (6) ◽  
pp. 856-860 ◽  
Author(s):  
Achim A. Jungbluth ◽  
Yao-Tseng Chen ◽  
Elisabeth Stockert ◽  
Klaus J. Busam ◽  
Denise Kolb ◽  
...  

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 126-126 ◽  
Author(s):  
David James VanderWeele ◽  
Stephanie McCann ◽  
Xiaobing Fan ◽  
Tatjana Antic ◽  
Yulei Jiang ◽  
...  

126 Background: Better methods are needed to assess prior to prostatectomy the risk of aggressive prostate cancer. Radiogenomics is a promising new paradigm that aims to gain molecular and genomic insights from clinical images. Loss of PTEN expression correlates with clinically aggressive disease and is associated with a 7-fold increase in the risk of prostate cancer death. Methods: From 38 patients who had undergone multi-parametric prostate MRI prior to prostatectomy, a pathologist and a radiologist simultaneously identified 45 peripheral-zone cancer regions of interest (ROIs). Histologic sections of the cancer foci underwent immunohistochemical analysis and were scored according to percent of tumor cells expressing PTEN as: negative (0-20%), mixed (20-80%), or positive (80-100%). From the MRI ROIs, the average and 10th percentile ADC values, T2-weighted signal-intensity histogram skewness, and quantitative perfusion parameters were calculated. Both dynamic perfusion two-compartment model and an empirical mathematical model (EMM) were used to fit the average contrast concentration curves within the ROIs as a function of time. Associations between the quantitative image features and PTEN expression were analyzed with Pearson's correlation coefficient (r). Results: The PTEN scores were: positive (n = 21, 47%), mixed (n = 12, 27%), and negative (n = 12, 27%). Two perfusion imaging contrast uptake parameters obtained from EMM correlated with PTEN scores (r = 0.25, p < 0.1 and r = 0.43, p < 0.01), and T2-weighted signal-intensity skewness also showed some correlation tendency (r = −0.25, p < 0.1). No correlation was seen between mean ADC and 10th percentile ADC values and PTEN score. Conclusions: This preliminary study of radiogenomics of prostate cancer suggests that fast contrast uptake of cancer on DCE-MR imaging and a T2-weighted imaging feature are potentially associated with prostate cancer PTEN expression, which warrants further studies and validation.


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