Blinded review of archival radical prostatectomy specimens supports that contemporary Gleason score 6 prostate cancer lacks metastatic potential

Bragayrac, Luciano A. Núñez; Murekeyisoni, Christine; Vacchio, Michael; Attwood, Kristopher; Mehedint, Diana; Mohler, James L.; Azabdaftari, Gissou; Xu, Bo; Kauffman, Eric

doi:10.1002/pros.23364

Cited by 9 publications

(9 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TMA demonstrated that the general expression of CEMIP in PCa tissue was substantially higher compared with that in their pericarcinous counterparts. Surprisingly, in the present work, the expression of CEMIP did not seem to be positively statistically correlated with GS, and some reports also observed that the current GS system might occasionally fail to represent-as an indicator-PCa progression and expression of certain oncogenes (31)(32)(33). Of note, CEMIP was indeed more intensively expressed in intermediate-and high-risk patients compared with their low-risk counterparts (data not shown).…”

Section: Discussioncontrasting

confidence: 79%

AMPK/GSK3β/β‐catenin cascade‐triggered overexpression of CEMIP promotes migration and invasion in anoikis‐resistant prostate cancer cells by enhancing metabolic reprogramming

et al. 2018

View full text Add to dashboard Cite

Prostate cancer (PCa) represents one of the most common solid neoplasms, and metastasis is the second leading cause of death in adult males. Anoikis is a programmed cell death that is induced upon cell detachment from the extracellular matrix (ECM), which behaves as a critical protective mechanism for anchorage-independent cell growth and metastasis formation. However, in the absence of ECM attachment, shift of metabolic pattern and tolerance to anoikis facilitate the survival of aggressive cancer cells in the circulatory system as well as their metastasis to distant sites. Few molecular targets in PCa have thus far been reported to prevent anoikis resistance, metabolic reprogramming, and metastasis simultaneously. In the present study, elevated migration, invasion, pyruvate production, lactate generation, ATP level, and impaired detachment-induced apoptosis were found in anoikis-resistant PCa cells, and genome microarray analysis demonstrated that the cell migration-inducing protein (CEMIP) was a potential molecular target for the regulation of the aforementioned malignant behaviors. Additional investigation revealed that the AMPK/glycogen synthase kinase 3β (GSK3β)/β-catenin cascade-triggered CEMIP overexpression in anoikis-resistant PCa cells might be implicated in local progression, metabolic shift, and cellular migration and invasion, whereas knockout of CEMIP by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 in anoikis-resistant PCa cells reversed the described bioeffects by reducing expressions of matrix metalloproteinase 2 (MMP2), VEGF, pyruvate dehydrogenase kinase isoform 4 (PDK4), and lactate dehydrogenase A. In addition, inhibition of glycolysis by CEMIP-mediated PDK4 down-regulation impaired the migration and invasion of anoikis-resistant PCa cells by attenuating MMP2 and VEGF expressions. Our findings establish that AMPK/GSK3β/β-catenin cascade-triggered CEMIP overexpression might promote migration and invasion in anoikis-resistant PCa cells by enhancing PDK4-associated metabolic reprogramming, which may provide a novel, promising therapeutic target for the treatment of advanced PCa.-Zhang, P., Song, Y., Sun, Y., Li, X., Chen, L., Yang, L., Xing, Y. AMPK/GSK3β/β-catenin cascade-triggered overexpression of CEMIP promotes migration and invasion in anoikis-resistant prostate cancer cells by enhancing metabolic reprogramming.

show abstract

Section: Discussioncontrasting

confidence: 79%

AMPK/GSK3β/β‐catenin cascade‐triggered overexpression of CEMIP promotes migration and invasion in anoikis‐resistant prostate cancer cells by enhancing metabolic reprogramming

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Evolving data have suggested that true Gleason score 6 prostate cancer does not have metastatic potential. 21 Although we did find men with Gleason score 6 prostate cancer at baseline in the metastatic disease cohort, we were not able to perform a contemporary pathologic review and many of these cases would likely be upgraded based on changes to Gleason scoring after the International Society of Urological Pathology report of 2005. 22 In addition, baseline risk in the current study was based on biopsy Gleason score and higher-grade tumors within the prostate may be missed after standard 12-needle core prostate biopsy.…”

Section: Discussionmentioning

confidence: 92%

Nine‐year prostate cancer survival differences between aggressive versus conservative therapy in men with advanced and metastatic prostate cancer

Dall′Era

Chen

et al. 2018

Cancer

View full text Add to dashboard Cite

The authors did not observe a survival advantage with local therapy in addition to standard androgen deprivation therapy for men with metastatic prostate cancer. However, the results of the current study did affirm advantages in the setting of locally advanced disease. Aggressive local therapy in the setting of metastatic disease needs to be studied carefully before clinical adoption. Cancer 2018;124:1921-8. © 2018 American Cancer Society.

show abstract

“…22 Beginning with the fourth TRUS biopsy, PSA kinet- Importantly, a review of Gleason score 6 radical prostatectomy (RP) specimens confirmed the absence of metastatic potential in these lesions. 25 1,3,9 Only 30% of men on AS in the PRIAS (Prostate Cancer Research International Active Surveillance) series followed for more than 4 years had undergone all of the biopsies recommended by study protocol. 26 In the future, genomic testing and MRI will play greater roles in patient selection and follow-up.…”

Section: Discussionmentioning

confidence: 99%

“…Tosoian et al reported that in favorable risk prostate cancer, the risk of progression to a lethal phenotype is low (0.4%) in the decade following diagnosis 9 . Importantly, a review of Gleason score 6 radical prostatectomy (RP) specimens confirmed the absence of metastatic potential in these lesions 25 . Following RP with Gleason score 6 histology a 0.2% cancer death rate was reported.…”

Section: Discussionmentioning

confidence: 99%

The impact of age on prostate cancer progression and quality of life in active surveillance patients

et al. 2020

View full text Add to dashboard Cite

Active surveillance (AS) represents a paradigm change in the management of low-risk prostate cancer. In appropriately selected patients, AS has been demonstrated to reduce the over-treatment of indolent prostate cancers with improvement in quality of life (QOL) with the caveat that the diagnosis of lethal malignancies remain feasible while the cancer remains curable. 1,2 Multiple AS studies have documented prostate cancer specific survival rates of 94-99.9% at 15 years with non-prostate cancer deaths being 9-24 times more likely. 3,4 AS protocols are hampered by a lack of consensus regarding standardized criteria for inclusion, follow-up, and the initiation of therapeutic intervention. 3-5 In particular, definitive local therapy is often recommended to healthy younger men with low-risk features due to a

show abstract

Blinded review of archival radical prostatectomy specimens supports that contemporary Gleason score 6 prostate cancer lacks metastatic potential

Abstract: Unbiased pathologist review of archival RP specimens supports absent metastatic potential for contemporarily defined GS6 CaP. Reduced postoperative monitoring is appropriate for pGS6, but may require pathology review to confirm absent Gleason pattern 4.

Cited by 9 publications

References 36 publications

AMPK/GSK3β/β‐catenin cascade‐triggered overexpression of CEMIP promotes migration and invasion in anoikis‐resistant prostate cancer cells by enhancing metabolic reprogramming

AMPK/GSK3β/β‐catenin cascade‐triggered overexpression of CEMIP promotes migration and invasion in anoikis‐resistant prostate cancer cells by enhancing metabolic reprogramming

Nine‐year prostate cancer survival differences between aggressive versus conservative therapy in men with advanced and metastatic prostate cancer

The impact of age on prostate cancer progression and quality of life in active surveillance patients

Contact Info

Product

Resources

About