Adenocarcinoma of the Prostate with Gleason Score 9-10 on Core Biopsy: Correlation with Findings at Radical Prostatectomy and Prognosis

Ellis, Carla LaShannon; Partin, Alan W.; Han, Misop; Epstein, Jonathan I.

doi:10.1016/j.juro.2013.05.056

Cited by 15 publications

(10 citation statements)

References 15 publications

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“…Because the postoperative determination of a tumors Gleason grade is "better" than the preoperatively determined Gleason grade (subjected to sampling errors and consequently undergrading in more than one third of cases; ref. 25), another multivariate analysis was added. In scenario 4, the preoperative Gleason grade obtained on the original biopsy was combined with preoperative PSA, cT stage, and p62 expression.…”

Section: Multivariate Analysismentioning

confidence: 99%

Cytoplasmic Accumulation of Sequestosome 1 (p62) Is a Predictor of Biochemical Recurrence, Rapid Tumor Cell Proliferation, and Genomic Instability in Prostate Cancer

Burdelski

Reiswich

Hube‐Magg

et al. 2015

Clinical Cancer Research

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Purpose: Sequestosome 1 (p62) is a multifunctional adapter protein accumulating in autophagy-defective cells.Experimental Design: To evaluate the clinical impact and relationship with key genomic alterations in prostate cancer, p62 protein levels were analyzed by immunohistochemistry on a tissue microarray containing 12,427 prostate cancers. Data on ERG status and deletions of PTEN, 3p13, 5q21, and 6q15 were available from earlier studies.Results: p62 immunostaining was absent in benign prostatic glands but present in 73% of 7,822 interpretable prostate cancers. Strong cytoplasmic p62 staining was tightly linked to high Gleason grade, advanced pathologic tumor (pT) stage, positive nodal status, positive resection margin, and early PSA recurrence (P < 0.0001 each). Increased levels of p62 were significantly linked to TMPRSS2-ERG fusions, both by FISH and immunohistochemical analysis (P < 0.0001 each). For example, moderate or strong p62 immunostaining was seen in 28.5% of cancers with TMPRSS2-ERG fusion detected by FISH and in 23.1% of cancers without such rearrangements (P < 0.0001). Strong p62 staining was significantly linked to the presence of all tested deletions, including PTEN (P < 0.0001), 6q15 (P < 0.0001), 5q21 (P ¼ 0.0002), 3p13 (P ¼ 0.0088), and 6q15 (P < 0.0001), suggesting a link between p62 accumulation and loss of genomic stability. The prognostic role of p62 protein accumulation was striking and independent of Gleason grade, pT stage, pN stage, surgical margin status, and preoperative PSA, regardless of whether preoperative or postoperative parameters were used for modeling.Conclusions: Our study identifies cytoplasmic accumulation of p62 as a strong predictor of an adverse prognostic behavior of prostate cancer independently from established clinicopathologic findings.

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Section: Multivariate Analysismentioning

confidence: 99%

Cytoplasmic Accumulation of Sequestosome 1 (p62) Is a Predictor of Biochemical Recurrence, Rapid Tumor Cell Proliferation, and Genomic Instability in Prostate Cancer

Burdelski

Reiswich

Hube‐Magg

et al. 2015

Clinical Cancer Research

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“…[1][2][3][4][5] Of particular significance is the accurate identification of high-grade Gleason pattern 5 (GP5), as it indicates the most aggressive and potentially lethal PCa. [6][7][8][9][10][11] The presence of GP5 in NBX essentially classifies the PCa into Gleason score 8 to 10, a group that has traditionally been defined in a high-grade category for patient management. Recent studies have further demonstrated prognostic value of stratifying Gleason score 8 from 9 to 10 PCa.…”

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confidence: 99%

Diagnosis of Gleason Pattern 5 Prostate Adenocarcinoma on Core Needle Biopsy

Shah¹,

Liu

et al. 2015

American Journal of Surgical Pathology

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Accurate recognition of Gleason pattern 5 (GP5) prostate adenocarcinoma on needle biopsy is critical as it is associated with disease progression and adverse clinical outcome. Despite important implications of this diagnosis, interobserver variation in the diagnosis of GP5 has not been adequately studied. Digital images of 66 prostate adenocarcinoma cases that potentially contained a GP5 component were distributed to 16 urologic pathologists who were asked to classify whether GP5 was present. Each image was initially classified into 1 of 4 morphologic subpatterns by 2 coauthors (R.B.S. and M.Z.): solid nests (15), comedocarcinoma (8), single cells and/or cords (35), and variant morphology (8). Additional features captured included: size (large: >20 cells, medium: 10 to 20 cells, and small: <10 cells) and distribution of nuclei (uniform vs. nonuniform) for nests pattern; intraluminal coagulative tumor necrosis, karyorrhectic debris, and amorphous material for comedocarcinoma pattern; and quantity (≤5, 6 to 10, and >10) and distribution (clustered vs. intermixed with adjacent well-formed glands) for single cells/cords pattern. Interobserver reproducibility of a diagnosis of GP5 was assessed and the morphologic subpatterns and features were correlated with the consensus diagnosis (defined as 75% agreement). Interobserver reproducibility for overall diagnostic agreement was fair (κ=0.376). Among subpatterns, comedocarcinoma had highest reproducibility (κ=0.499), followed by variant morphology (κ=0.443), single cells/cords (κ=0.369), and nests (κ=0.347). All cases with the following features achieved consensus for GP5: large nests regardless of nuclear distribution; coagulative necrosis with or without karyorrhectic debris; single cells/cords >10 or 6 to 10 in a cluster; and signet ring-like cells in single cells or within nests pattern. A majority of cases with the following features achieved consensus against GP5: medium-size nests; exclusive intraluminal amorphous material; single cells/cords ≤5; and Paneth cell change. Remaining morphologic features did not reach consensus for or against GP5. A majority (86%) of participants would diagnose a small focus of GP5 only when it is present in >1 level. The diagnostic reproducibility of GP5 within certain morphologies was only fair among urologic pathologists. However, the diagnosis of GP5 was more reproducible when certain restrictive morphologic and quantitative criteria were applied. These findings suggest that additional studies are needed to find highly reproducible features of GP5 associated with documented aggressive clinical outcome.

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“…9 In our study, the patients with GS ≥ 8 had tendency to be in clinical T2c-T3b stage compared to be in clinical T1-2a stage. In GS ≥ 8 group, the percentage of the patients with PSA > 20 ng/ml and with PSA ≤ 10 ng/ml were 45% and 23%, respectively.…”

Section: Discussionmentioning

confidence: 47%

Three Dimensional Conformal Radiotherapy and Androgen Deprivation Therapy in Patients with Clinically Localized Prostate Cancer; Hacettepe University Experience

Özdemir¹,

Akyol²,

Özyiğit³

et al. 2015

UHOD

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The aim of this study is to evaluate the treatment results of three dimensional conformal radiotherapy (3DCRT) and androgen deprivation therapy (ADT) in patients with clinically localized prostate cancer (CLPC). Between June 1998 and December 2011, 577 patients with the diagnosis of CLPC were treated. ADT was started 3 months prior to radiotherapy (RT). 3DCRT was delivered to prostate and the seminal vesicles (SV) to a total dose of 70Gy. Additionally, patients with lymph node (LN) positivity received 50.4Gy RT to pelvic LN's. Median follow up time was 65 months. Five-ten years overall survival (OS), cause specific survival (CSS), PSA relapse-free survival (PSA-RFS) and distant metastasis-free survival (DMFS) rates were 92-74%, 97-91%, 77-55% and 94-88%, respectively. OS was negatively affected from LN positivity (p< 0.001). In the subgroup of patients with GS≥ 8, there was no significant difference between < 1 years and ≥ 1 years of ADT in terms of CSS, PSA-RFS and DMFS. OS was better in patients with < 1 years of ADT (p= 0.01). Five year OS (p= 0.02), CSS (p= 0.05), PSA-RFS (p= 0.01) and DMFS (p= 0.07) rates were inferior in the high risk group patients that used ADT ≥ 1 year. Acute and late RTOG grade III/IV gastrointestinal system toxicity rates were 1.7% and 5% and acute and chronic RTOG grade III/IV genitourinary system toxicity rates were 1.4% and 5%, respectively. 3DCRT and ADT combination is an effective treatment modality with acceptable toxicities in patients with clinically localized prostate cancer. Keywords: Prostate cancer, Conformal radiotherapy, Androgen deprivation therapy ÖZET Lokalize Prostat Kanserli Olgularda Üç Boyutlu Konformal Radyoterapi ve Total Androjen Blokajı; Hacettepe Üniversi-tesi DeneyimiBu çalışmanın amacı, üç boyutlu konformal radyoterapi (3BKRT) ve total androjen blokajı (TAB) Lokalize prostat kanserli olgularımızdaki tedavi sonuçlarımızı değerlendirmek. Haziran 1998 ve Aralık 2011 tarihleri arasında lokalize prostat kanseri tanısıyla 577 olgu tedavi edildi. TAB tedavisine radyoterapiden (RT) 3 ay sonar başlandı. 3BKRT olarak prostat ve seminal veziküllere toplam 70 Gy uygulandı. Ek olarak lenf nodu (LN) tutulumu olan olgularda pelvic LN'larına 50.4 Gy uygulandı. Ortanca izlem süresi 65 aydır. Beş-on yıllık genel sağkalım (GS), hastalığa özgü sağkalım (HSS), PSA-relapssız sağkalım (PSA-RFS) ve uzak metastazsız sağkalım (DMFS) oranları sırasıyla %92-74, %97-91, %77-55 ve %94-88 bulundu. LN tutulumu GS'ı olumsuz etkilemiştir (p< 0.001). Gleason skoru ≥ 8 olan olgularda <1 yıl ile ≥ 1yıl TAB kullanımı arasında HSS, PSA-RFS ve DMFS açısından fark yoktu. Ancak <1 yıl TAB kullananlarda GS daha iyiydi (p= 0.01). Yüksek riskli grupta olup ≥ 1yıl TAB kullanan hastalarda 5 yıllık GS (p= 0.02), HSS (p= 0.05), PSA-RFS (p= 0.01) ve DMFS (p= 0.07) daha düşük bulundu. Erken ve geç dönem RTOG grad III/IV gastrointestinal sistem toksisite oranları %1.7 ve %5 bulundu. Erken ve geç dönem RTOG grad III/IV genitoüriner sistem toksisite oranları %1.4 ve %5 bulundu. Lokalize prostat kanseri...

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Adenocarcinoma of the Prostate with Gleason Score 9-10 on Core Biopsy: Correlation with Findings at Radical Prostatectomy and Prognosis

Abstract: In the highly select subset of patients who are good surgical candidates and have the appropriate combination of preoperative variables postoperative findings are sufficiently favorable to justify radical prostatectomy.

Cited by 15 publications

References 15 publications

Cytoplasmic Accumulation of Sequestosome 1 (p62) Is a Predictor of Biochemical Recurrence, Rapid Tumor Cell Proliferation, and Genomic Instability in Prostate Cancer

Cytoplasmic Accumulation of Sequestosome 1 (p62) Is a Predictor of Biochemical Recurrence, Rapid Tumor Cell Proliferation, and Genomic Instability in Prostate Cancer

Diagnosis of Gleason Pattern 5 Prostate Adenocarcinoma on Core Needle Biopsy

Three Dimensional Conformal Radiotherapy and Androgen Deprivation Therapy in Patients with Clinically Localized Prostate Cancer; Hacettepe University Experience

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