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      Concordance of cribriform architecture in matched prostate cancer biopsy and radical prostatectomy specimens

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          Abstract

          Aims

          Invasive cribriform and/or intraductal carcinoma have been identified as independent adverse parameters for prostate cancer outcome. Little is known on biopsy undersampling of cribriform architecture. Our aim was to determine the extent of cribriform architecture undersampling and to find predictive factors for identifying false cribriform‐negative cases.

          Methods and results

          We reviewed 186 matched prostate biopsies and radical prostatectomy specimens. Of 97 biopsy grade group 2 (Gleason score 3 + 4 = 7) patients, 22 (23%) had true cribriform‐negative (TN), 39 (40%) false‐negative (FN) and 36 (37%) true‐positive (TP) biopsies. Patients with FN biopsies had higher, although not statistically significant ( P = 0.06), median PSA levels than patients with TP biopsies (12 versus 8 ng/ml). A PI‐RADS 5 lesion was present in nine of 16 (54%) FN and three of 11 (27%) TN biopsies ( P = 0.05). Positive biopsy rate ( P = 0.47), percentage Gleason pattern 4 ( P = 0.55) and glomeruloid architecture ( P = 1.0) were not different. Logistic regression identified PSA as an independent predictor (odds ratio = 3.5; 95% confidence interval = 1.2–9.4, P = 0.02) for cribriform architecture on radical prostatectomy, but not PI‐RADS score. The FN rate for large cribriform architecture at radical prostatectomy was 27%, which was lower than for any cribriform architecture ( P = 0.01). During follow‐up (median 27 months), biochemical recurrence‐free survival of patients with TP biopsies was significantly shorter than that of those with FN biopsies ( P = 0.03).

          Conclusion

          In conclusion, 40% of grade group 2 prostate cancer biopsies were FN for cribriform architecture. These patients had higher PSA levels and more frequent PI‐RADS score 5 lesions than men with TN biopsies.

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          Most cited references20

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          Upgrading and downgrading of prostate cancer from biopsy to radical prostatectomy: incidence and predictive factors using the modified Gleason grading system and factoring in tertiary grades.

          Prior studies assessing the correlation of Gleason score (GS) at needle biopsy and corresponding radical prostatectomy (RP) predated the use of the modified Gleason scoring system and did not factor in tertiary grade patterns. To assess the relation of biopsy and RP grade in the largest study to date. A total of 7643 totally embedded RP and corresponding needle biopsies (2004-2010) were analyzed according to the updated Gleason system. All patients underwent prostate biopsy prior to RP. The relation of upgrading or downgrading to patient and cancer characteristics was compared using the chi-square test, Student t test, and multivariable logistic regression. A total of 36.3% of cases were upgraded from a needle biopsy GS 5-6 to a higher grade at RP (11.2% with GS 6 plus tertiary). Half of the cases had matching GS 3+4=7 at biopsy and RP with an approximately equal number of cases downgraded and upgraded at RP. With biopsy GS 4+3=7, RP GS was almost equally 3+4=7 and 4+3=7. Biopsy GS 8 led to an almost equal distribution between RP GS 4+3=7, 8, and 9-10. A total of 58% of the cases had matching GS 9-10 at biopsy and RP. In multivariable analysis, increasing age (p<0.0001), increasing serum prostate-specific antigen level (p<0.0001), decreasing RP weight (p<0.0001), and increasing maximum percentage cancer/core (p<0.0001) predicted the upgrade from biopsy GS 5-6 to higher at RP. Despite factoring in multiple variables including the number of positive cores and the maximum percentage of cancer per core, the concordance indexes were not sufficiently high to justify the use of nomograms for predicting upgrading and downgrading for the individual patient. Almost 20% of RP cases have tertiary patterns. A needle biopsy can sample a tertiary higher Gleason pattern in the RP, which is then not recorded in the standard GS reporting, resulting in an apparent overgrading on the needle biopsy. Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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            Clinical Utility of Quantitative Gleason Grading in Prostate Biopsies and Prostatectomy Specimens.

            Gleason grading is the strongest prognostic parameter in prostate cancer. Gleason grading is categorized as Gleason ≤ 6, 3 + 4, 4 + 3, 8, and 9-10, but there is variability within these subgroups. For example, Gleason 4 components may range from 5-45% in a Gleason 3 + 4 = 7 cancer.
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              Cribriform growth is highly predictive for postoperative metastasis and disease-specific death in Gleason score 7 prostate cancer.

              Patients with Gleason score 7 prostate cancer on radical prostatectomy demonstrate a wide range in clinical outcome. Gleason grade 4 prostate cancer encompasses a heterogeneous group of tumor growth patterns including fused, ill-defined, cribriform, and glomeruloid glandular structures. Our objective was to determine the prognostic value of different Gleason grade 4 growth patterns. We performed a nested case-control study among 535 patients with Gleason score 7 prostate cancer at radical prostatectomy, treated between March 1985 and July 2013 at a university hospital in the Netherlands. We analyzed 52 cases (with metastasis, disease-specific mortality or both) and 109 controls, matched for age, PSA level, and pT stage. Presence of the following Gleason grade 4 patterns was recorded: fused, ill-defined, cribriform, and glomeruloid. Intraductal carcinoma of the prostate and tertiary Gleason grade 5 were additionally assessed. Outcomes were metastasis-free survival and disease-specific survival. We used Cox proportional hazards regression to determine the predictive value of Gleason grade 4 patterns for survival time. The overall prevalence of Gleason grade 4 patterns was as follows: fused 75% (n=121), ill-defined 64% (n=102), cribriform 48% (n=83), and glomeruloid 25% (n=40). Cribriform pattern was the only pattern with an unequal distribution between cases and controls. Forty-two out of 52 cases (81%) had cribriform growth pattern versus 41/109 controls (38%). In multivariate analysis, presence of cribriform growth was an adverse independent predictor for distant metastasis-free survival (HR 8.0, 95% CI 3.0-21; P<0.001) and disease-specific survival (HR 5.4, 95% CI 2.0-15, P=0.001). In conclusion, cribriform growth in Gleason grade 4 is a strong prognostic marker for distant metastasis and disease-specific death in patients with Gleason score 7 prostate cancer at radical prostatectomy.
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                Author and article information

                Contributors
                e.hollemans@erasmusmc.nl
                Journal
                Histopathology
                Histopathology
                10.1111/(ISSN)1365-2559
                HIS
                Histopathology
                John Wiley and Sons Inc. (Hoboken )
                0309-0167
                1365-2559
                02 August 2019
                September 2019
                : 75
                : 3 ( doiID: 10.1111/his.v75.3 )
                : 338-345
                Affiliations
                [ 1 ] Department of Pathology Erasmus MC University Medical Center Rotterdam the Netherlands
                [ 2 ] Department of Urology Erasmus MC University Medical Center Rotterdam the Netherlands
                [ 3 ] Department of Radiology Erasmus MC University Medical Center Rotterdam the Netherlands
                [ 4 ] Department of Urology Franciscus Gasthuis and Vlietland Rotterdam the Netherlands
                Author notes
                [*] [* ] Address for correspondence: E Hollemans, Department of Pathology, Erasmus MC University Medical Center, PO Box 2040, 3000 CA Rotterdam, the Netherlands. e‐mail: e.hollemans@ 123456erasmusmc.nl

                [†]

                These authors contributed equally to this study.

                Author information
                https://orcid.org/0000-0003-2406-5370
                https://orcid.org/0000-0002-2734-0254
                https://orcid.org/0000-0003-2176-9102
                Article
                HIS13893
                10.1111/his.13893
                6851781
                31045262
                9443e352-b1c5-43fb-8b91-23435477b218
                © 2019 The Authors. Histopathology Published by John Wiley & Sons Ltd

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 March 2019
                : 29 April 2019
                Page count
                Figures: 1, Tables: 3, Pages: 8, Words: 5294
                Funding
                Funded by: Jaap Schouten Foundation
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                September 2019
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.1 mode:remove_FC converted:13.11.2019

                Pathology
                biopsy,cribriform,outcome,prostate cancer,radical prostatectomy
                Pathology
                biopsy, cribriform, outcome, prostate cancer, radical prostatectomy

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