Differential Immunohistochemical Profiles for Distinguishing Prostate Carcinoma and Urothelial Carcinoma

Oh, Woo Jin; Chung, Arthur Minwoo; Kim, Jee Soon; Han, Ji Heun; Hong, Sung Hoo; Lee, Ji Yeol; Choi, Yeong Jin

doi:10.4132/jptm.2016.06.14

Cited by 38 publications

(53 citation statements)

References 27 publications

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“…Follow-up prostate-specific diagnostic tests including biopsy were recommended for all men with ICC-PSA-positive-CTC (80%, n = 20/25). This group included a man of Asian background with ICC-PSA-negative-CTC, as the specificity of the PSA-marker is lower (90%) in an Asian population compared to 97% in Caucasians (45).…”

Section: Early Detection Of Cancer In Screened Patients (Group Ed)mentioning

confidence: 99%

New Screening Test Improves Detection of Prostate Cancer Using Circulating Tumor Cells and Prostate-Specific Markers

et al. 2020

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The current screening-test for prostate cancer, affecting 10% of men worldwide, has a high false negative rate and a low true positive rate. A more reliable screening test is needed. Circulating-Tumor-Cells (CTC) provide a biomarker for early carcinogenesis, cancer progression and treatment effectiveness. The cytology-based ISET ® -CTC Test is a clinically validated blood test with high sensitivity and specificity. This study aimed to evaluate the ISET ® -CTC test combined with prostate-specific-marker staining as a screening test for the detection of prostate cancer. We selected a group of 47 men from our ongoing CTC screening study involving 2,000 patient-tests from Sep-2014 to July-2019, who also underwent standard diagnostic cancer testing before or after CTC testing. While 20 of the 47 men were diagnosed with prostate cancer before the ISET ® -CTC test, 27 men underwent screening. We studied the CTC identified in 45 CTC-positive men by Immuno-Cyto-Chemistry (ICC) assays with the prostate-specific-marker PSA. CTC were ICC-PSA-marker positive in all men diagnosed with primary prostate cancer (n = 20). Secondary cancers were detected in 63% (n = 7/11) of men with mixed CTC-population (ICC-PSA-positive/ICC-PSA-negative). Of the 27 men screened, 25 had CTC, and 84% of those (n = 20) were positive for the prostate-specific-PSA-marker. Follow-up testing suggested suspected prostate cancer in 20/20 men by a positive PSMA-PET scan, and biopsies performed in 45% (n = 9/20) men confirmed the diagnosis of early prostate cancer. Kidney cancer or B-cell lymphoma were detected in two men with ICC-PSA-marker negative CTC. Our study suggests that the combination of ISET ® -CTC and ICC-PSA-marker-testing has an estimated positive-predictive-value (PPV) of 99% and a negative-predictive-value (NPV) of 97%, providing a more reliable screening test for prostate cancer than the standard PSA-blood-test (PPV = 25%; NPV = 15.5%). Our findings warrant further studies to evaluate the new test's potential for prostate cancer screening on a population level.

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Section: Early Detection Of Cancer In Screened Patients (Group Ed)mentioning

confidence: 99%

New Screening Test Improves Detection of Prostate Cancer Using Circulating Tumor Cells and Prostate-Specific Markers

et al. 2020

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“…There is scarce literature describing Nkx3.1 expression specifically in the bladder. In fact, NKX3.1 positivity has been shown to be a useful adjunct marker in differentiating prostate and urothelial carcinomas (29,30). At baseline, we observed low levels of Nkx3.1 expression in the bladder and surprisingly an effect on Col7α1 expression in the knockout.…”

Section: Discussionmentioning

confidence: 60%

The Homeodomain Transcription Factor NKX3.1 Modulates Bladder Outlet Obstruction Induced Fibrosis in Mice

et al. 2019

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Fibrosis is an irreversible remodeling process characterized by the deposition of collagen in the extracellular matrix of various organs through a variety of pathologies in children, leading to the stiffening of healthy tissues and organ dysfunction. Despite the prevalence of fibrotic disease in children, large gaps exist in our understanding of the mechanisms that lead to fibrosis, and there are currently no therapies to treat or reverse it. We previously observed that castration significantly reduces fibrosis in the bladders of male mice that have been partially obstructed. Here, we investigated if the expression of androgen response genes were altered in mouse bladders after partial bladder outlet obstruction (PO). Using a QPCR microarray and QRTPCR we found that PO was sufficient to increase expression of the androgen response gene Nkx3.1. Consistent with this was an increase in the expression of NKX3.1 protein. Immunofluorescent antibody localization demonstrated nuclear NKX3.1 in most bladder cells after PO. We tested if genetic deletion of Nkx3.1 alters remodeling of the bladder wall after PO. After PO, Nkx3.1KO/KO bladders underwent remodeling, demonstrating smaller bladder area, thickness, and bladder: body weight ratios than obstructed, wild type controls. Remarkably, Nkx3.1KO/KO specifically affected histological parameters of fibrosis, including reduced collagen to muscle ratio. Loss of Nkx3.1 altered collagen and smooth muscle cytoskeletal gene expression following PO which supported our histologic findings. Together these findings indicated that after PO, Nkx3.1 expression is induced in the bladder and that it mediates important pathways that lead to tissue fibrosis. As Nkx3.1 is an androgen response gene, our data suggest a possible mechanism by which fibrosis is mediated in male mice and opens the possibility of a molecular pathway mediated by NKX3.1 that could explain sexual dimorphism in bladder fibrosis.

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“…In the current study, GATA3 had high sensitivity in urothelial carcinoma among all published studies, where it was 96% (49/51) that was close to Clark et al [19] study 95% (21/22), Miettinen et al [23] study 90% (49/54), and Leivo et al [20] study 99% (88/89), who used the same source of primary antibody (Bio SB, Clone L50-823) of our study. This differs from GATA3 sensitivity in two larger studies, Higgins et al [21] found 67% of 308 cases and Oh et al [17] found 84.8% of 138 cases. The difference may be excused due to larger study groups, different primary antibody source, and inherent nature of tissue blocks.…”

Section: Discussionmentioning

confidence: 65%

“…In reviewing previous studies, most analyzed GATA3 expression using different scoring methods. Oh et al [17] depended on more than 10% of cells stained to be positive regardless intensity. Liu et al [18] considered <5% of cells stained to be a negative result.…”

Section: Discussionmentioning

confidence: 99%

Applying Gata3 in Differentiating Urothelial Carcinoma From Prostatic Adenocarcinoma: An Immunohistochemical Study

Abdullah

Kerbel

Husseini

2018

Asian J Pharm Clin Res

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Objectives: Urothelial carcinoma and prostatic adenocarcinoma are the most common tumors of genitourinary system. Both tumors can demonstrate a broad morphology or present as poorly differentiated carcinoma occurring in urinary bladder or prostate or both organs that raise the suspicion of a locally extending or metastatic carcinoma from either organs. Accurate distinction between these tumors is mandatory because of different tumor biology and therapeutic protocols. In equivocal tumor morphology, the primary option is to use immunohistochemical panel in surgical pathology that includes differentiation markers that will assist pathologists to avoid misdiagnosis. The aim of this study is immunohistochemical evaluation of GATA3 in urothelial carcinoma and prostatic adenocarcinoma with correlation to different clinicopathological parameters.Methods: We used formalin-fixed paraffin-embedded tissue blocks from 51 patients of urothelial carcinoma and 15 patients of prostatic adenocarcinoma including different grades, stages, and types. Monoclonal antibody for GATA3 was used for immunohistochemical staining of tissue sections, and GATA3 expression was semi-quantitatively scored using H-score method.Results: Of 51 urothelial carcinomas, 96% were GATA3 positive with a mean H-score = 212. No correlation between GATA3 expression and clinicopathological parameters includes grade and stage. Lower GATA3 expression was noted in urothelial carcinoma variants. All of prostatic adenocarcinoma cases did not show GATA3 reactivity.Conclusion: GATA3 reactivity is a reliable factor to confirm diagnosis of urothelial carcinoma and exclude prostatic adenocarcinoma. The routine use of GATA3 as differentiation marker for urothelial carcinoma may be advocated based on the results of this study.

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Differential Immunohistochemical Profiles for Distinguishing Prostate Carcinoma and Urothelial Carcinoma

Cited by 38 publications

References 27 publications

New Screening Test Improves Detection of Prostate Cancer Using Circulating Tumor Cells and Prostate-Specific Markers

New Screening Test Improves Detection of Prostate Cancer Using Circulating Tumor Cells and Prostate-Specific Markers

The Homeodomain Transcription Factor NKX3.1 Modulates Bladder Outlet Obstruction Induced Fibrosis in Mice

Applying Gata3 in Differentiating Urothelial Carcinoma From Prostatic Adenocarcinoma: An Immunohistochemical Study

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