Architectural Heterogeneity and Cribriform Pattern Predict Adverse Clinical Outcome for Gleason Grade 4 Prostatic Adenocarcinoma

Dong, Fei; Yang, Ping; Wang, Chaofu; Wu, Shulin; Xiao, Yu; McDougal, W. Scott; Young, Robert H.; Wu, Chin‐Lee

doi:10.1097/pas.0b013e3182a02169

Cited by 118 publications

(119 citation statements)

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“…Presence and prevalence of cribriform and/or IDC architecture was confirmed in prostate tumors, similar to previous studies on architectural patterns in PCa RPs (10)(11)(12)(13)(14)(15)(16)(17). Furthermore, a significant increase in APC, RASSF1 and TBX15 methylation in association with cribriform/IDC features was demonstrated.…”

Section: Median Pmr Values ------------------------------------------supporting

confidence: 73%

“…Studies have demonstrated that IDC in biopsy and/or RP tissues is indicative of a possible adverse clinical course and metastatic disease, warranting further aggressive treatment (10)(11)(12)(13). Similarly, cribriform architecture has been demonstrated to be a clinically significant independent prognosticator for PCa-specific mortality (14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

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Distinct DNA methylation alterations are associated with cribriform architecture and intraductal carcinoma in Gleason pattern 4 prostate tumors

et al. 2017

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Abstract. The aim of the present study was to explore DNA methylation aberrations in association with cribriform architecture and intraductal carcinoma (IDC) of the prostate, as there is robust evidence that these morphological features are associated with aggressive disease and have significant clinical implications. Herein, the associations of a panel of seven known prognostic DNA methylation biomarkers with cribriform and IDC features were examined in a series of 91 Gleason pattern (GP) 4 tumors derived from Gleason score 7 radical prostatectomies. Gene specific DNA methylation was compared between cribriform and/or IDC positive vs. negative cases, and in association with clinicopathological features, using Chi square and Mann-Whitney U tests. DNA methylation of the adenomatous polyposis coli, Ras association domain family member 1 and T-box 15 genes was significantly elevated in GP4 tumors with cribriform and/or IDC features compared with negative cases (P=0.045, P=0.007 and P=0.013, respectively). To the best of our knowledge, this provides the first evidence for an association between cribriform and/or IDC and methylation biomarkers, and warrants further investigation of additional DNA methylation events in association with various architectural patterns in prostate cancer. IntroductionProstate cancer (PCa) is the second most common type of cancer affecting men worldwide, with an incidence of 1.1 million new cases each year (1). The most widely accepted pathological grading of PCa is the Gleason Score (GS), which is based on architectural features of the gland and is comprised of the sum of two Gleason Patterns (GP) (2). The GS grading system is among the most effective predictors of clinical outcomes following radical prostatectomy (RP), and is universally used to guide PCa treatment (3). Within this system, GS6 PCas are low grade, whereas GS8 or higher are classified as high grade. GS7 prostate adenocarcinomas consisting of variable proportions of GP3 and GP4 are considered to be intermediate grade, and represent the most heterogeneous group of neoplasms with diverse clinical outcomes (4,5) Thus, GS7 PCa is the focus of the current study, as identifying specific prognostic factors that can provide additional information on disease progression and treatment outcomes for patients with GS7 PCa would be of marked clinical benefit. GP4 is assigned to adenocarcinomas when they contain any of the following architectural patterns: Small/large fused glands, poorly formed glands, glomeruloid and cribriform architecture (4-6). The cribriform pattern is commonly associated with intraductal carcinoma (IDC), a distinct histopathological entity characterized by malignant cells spanning the lumen of prostate ducts and acini (7-9). Although specific morphologies of PCa, including cribriform architecture and IDC, have been recognized for decades, their independent clinical significance is only now emerging (8). Studies have demonstrated that IDC in biopsy and/or RP tissues is indicative Distinct DNA methylation alteration...

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Section: Median Pmr Values ------------------------------------------supporting

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Distinct DNA methylation alterations are associated with cribriform architecture and intraductal carcinoma in Gleason pattern 4 prostate tumors

et al. 2017

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“…Dong et al 19 found that metastasis occurred five times more frequently in patients with cribriform pattern at radical prostatectomy (13% vs 2.6% when cribriform pattern is absent) in a consecutive series of 241 patients. These results are well in line with the findings of the current study.…”

Section: Discussionmentioning

confidence: 99%

Cribriform growth is highly predictive for postoperative metastasis and disease-specific death in Gleason score 7 prostate cancer

et al. 2015

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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, diseasespecific 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 ¼ 121), ill-defined 64% (n ¼ 102), cribriform 48% (n ¼ 83), and glomeruloid 25% (n ¼ 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; Po0.001) and disease-specific survival (HR 5.4, 95% CI 2.0-15, P ¼ 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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“…Nevertheless, recent data from several institutions have clearly demonstrated that cribriform adenocarcinoma is independently associated with biochemical failure after RP [25,26], with metastasis after RP [27], and with metastasis-free and disease-specific survival [27]. All cribriform adenocarcinomas should be assigned pattern 4.…”

Section: Immunophenotypementioning

confidence: 99%

The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs—Part B: Prostate and Bladder Tumours

et al. 2016

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It has been 12 yr since the publication of the last World Health Organization (WHO) classification of tumours of the prostate and bladder. During this time, significant new knowledge has been generated about the pathology and genetics of these tumours. Intraductal carcinoma of the prostate is a newly recognized entity in the 2016 WHO classification. In most cases, it represents intraductal spread of aggressive prostatic carcinoma and should be separated from high-grade prostatic intraepithelial neoplasia. New acinar adenocarcinoma variants are microcystic adenocarcinoma and pleomorphic giant cell adenocarcinoma. Modifications to the Gleason grading system are incorporated into the 2016 WHO section on grading of prostate cancer, and it is recommended that the percentage of pattern 4 should be reported for Gleason score 7. The new WHO classification further recommends the recently developed prostate cancer grade grouping with five grade groups. For bladder cancer, the 2016 WHO classification continues to recommend the 1997 International Society of Urological Pathology grading classification. Newly described or better defined noninvasive urothelial lesions include urothelial dysplasia and urothelial proliferation of uncertain malignant potential, which is frequently identified in patients with a prior history of urothelial carcinoma. Invasive urothelial carcinoma with divergent differentiation refers to tumours with some percentage of "usual type" urothelial carcinoma combined with other morphologies. Pathologists should mention the percentage of divergent histologies in the pathology report. PATIENT SUMMARY Intraductal carcinoma of the prostate is a newly recognized entity in the 2016 World Health Organization classification. Better defined noninvasive urothelial lesions include urothelial dysplasia and urothelial proliferation of uncertain malignant potential. v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j AbstractIt has been 12 yr since the publication of the last World Health Organization (WHO) classification of tumours of the prostate and bladder. During this time, significant new knowledge has been generated about the pathology and genetics of these tumours.

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Architectural Heterogeneity and Cribriform Pattern Predict Adverse Clinical Outcome for Gleason Grade 4 Prostatic Adenocarcinoma

Cited by 118 publications

References 6 publications

Distinct DNA methylation alterations are associated with cribriform architecture and intraductal carcinoma in Gleason pattern 4 prostate tumors

Distinct DNA methylation alterations are associated with cribriform architecture and intraductal carcinoma in Gleason pattern 4 prostate tumors

Cribriform growth is highly predictive for postoperative metastasis and disease-specific death in Gleason score 7 prostate cancer

The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs—Part B: Prostate and Bladder Tumours

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