Genomics. He WW, Sciavolino PJ, Wing J, Augustus M, Hudson P, Meissner PS, Curtis RT, Shell BK, Bostwick DG, Tindall DJ, Gelmann EP, Abate-Shen C, Carter KC. 2015;161:1215–28. 2016;7(10):11165–93. Corso G, Carvalho J, Marrelli D, Vindigni C, Carvalho B, Seruca R, Roviello F, Oliveira C. Somatic mutations and deletions of the E-cadherin gene predict poor survival of patients with gastric cancer. Nat Genet. Kryvenko ON, Gupta NS, Virani N, Schultz D, Gomez J, Amin A, Lane Z, Epstein JI. 8 with and 30 without CR/IDC was too low for statistical analysis. 2016;70:549–52. There are even rarer forms of adenocarcinoma, including mucinous (colloid) carcinoma, cribriform carcinoma, squamous cell cancer, sarcomatoid carcinoma, carcinosarcoma, and prostate … Friedlander TW, Roy R, Tomlins SA, Ngo VT, Kobayashi Y, Azameera A, Rubin MA, Pienta KJ, Chinnaiyan A, Ittmann MM, Ryan CJ, Paris PL. On the other hand, we did not find a statistically significant difference between GS 3 + 4 = 7 without CR/IDC and GS 6 cases, which further supports the question whether it is clinically relevant to distinguish CR/IDC-negative GS 3 + 4 = 7 from GS 6 prostate cancer cases. Elucidation of the molecular alterations associated to CR/IDC is not only of interest for molecular-biology, but might also have future impact for prostate cancer diagnosis and management. Google Scholar. Oncogene. Oncotarget. Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner SH, Giovanella BC, Ittmann M, Tycko B, Hibshoosh H, Wigler MH, Parsons R. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. In total 474 deleted and 328 amplified genes were validated in the CPC-GENE cohort (q < 0.1), located on chromosomes 8p, 10q23, 13q22, 16q23–24, 17p13, 21q22, as well as 8q24, respectively (Additional file 5: Table S4 and Additional file 6: Figure S7). “Nimbosus”: genomic instability and SChLAP1 Dysregulation underpin aggression of Intraductal and Cribriform subpathologies. Evaluation of PPP2R2A as a prostate cancer susceptibility gene: a comprehensive germline and somatic study. Genes Chromosomes Cancer. To determine whether genomic instability in CR/IDC was a global phenomenon or affected specific genomic regions, we computed PGA for individual chromosome arms utilizing deletion and amplification events independently. amplifications_case – number of CR/IDC positive samples with an amplification spanning gene locus, amplifications_control – number of control samples with an amplification spanning gene locus, cases – total number of CR/IDC positive samples, controls – total number of control samples. Increased PGA for chromosome 4p, 8p, 10q, 12p and 16q deletions were also present in the CPC-GENE cohort (p < 0.05, Additional file 1: Figs. Cribriform architecture in the context of prostate cancer is characterized by an expansile, sieve-like proliferation of malignant epithelial cells having a “glands-within-glands appearance” that frequently spans the width of a prostate … Feik E, Schweifer N, Baierl A, Sommergruber W, Haslinger C, Hofer P, Maj-Hes A, Madersbacher S, Gsur A. Integrative analysis of prostate cancer aggressiveness. Recently, Chua et al. Epstein JI, Egevad L, Amin MB, Delahunt B, Srigley JR, Humphrey PA. While we set out to validate our findings in an independent cohort, we noticed that many events originally found in the TCGA cohort could not be confirmed in the CPC-GENE dataset. Humphrey, P. A. Punctuated evolution of prostate cancer genomes. Prostate. BMC Bioinformatics. 30100 Telegraph Road, Suite 408, Bingham Farms, Michigan 48025 (USA). 62, 63 Among others, deletions of 8p and 10q and amplification of 8q24 corresponding to PTEN loss and c‐MYC gain were significantly enriched in cribriform carcinoma… Kweldam CF, Kümmerlin IP, Nieboer D, Verhoef EI, Steyerberg EW, van der Kwast TH, Roobol MJ, van Leenders GJ. Br J Cancer. 2012;487:239–43. Mol Cell. Disease-specific death and metastasis do not occur in patients with Gleason score ≤6 at radical prostatectomy. Copy number analysis indicates monoclonal origin of lethal metastatic prostate cancer. Overview heatmap of CNA in TCGA cohort. Genomic instability was calculated based on a modified PGA formula (see methods). Although genetic deletions of genes located between the TMPRSS2 promoter and ERG occurred more frequently in CR/IDC cases, we were unable to find a significant difference in ERG mRNA expression (Additional file 1: Figure S6). PubMed Central  Intraductal carcinoma of the prostate without invasive carcinoma on needle biopsy: emphasis on radical prostatectomy findings. 2015;137:2354–63. Identification of molecular alterations associated with CR/IDC in voided urine could form the base of non-invasive tests for detection of aggressive CR/IDC. statement and Cribriform neoplasia of the prostate can be recognized easily. Yamamoto F, Yamamoto M. Scanning copy number and gene expression on the 18q21-qter chromosomal region by the systematic multiplex PCR and reverse transcription-PCR methods. Kweldam CF, Wildhagen MF, Bangma CH, van Leenders GJLH. Iczkowski KA, Torkko KC, Kotnis GR, Wilson RS, Huang W, Wheeler TM, Abeyta AM, La Rosa FG, Cook S, Werahera PN, Lucia MS. Digital quantification of five high-grade prostate cancer patterns, including the cribriform pattern, and their association with adverse outcome. Robinson D, Van Allen EM, Y-M W, Schultz N, Lonigro RJ, Mosquera J-M, Montgomery B, Taplin M-E, Pritchard CC, Attard G, Beltran H, Abida W, Bradley RK, Vinson J, Cao X, Vats P, Kunju LP, Hussain M, Feng FY, Tomlins SA, Cooney KA, Smith DC, Brennan C, Siddiqui J, Mehra R, Chen Y, Rathkopf DE, Morris MJ, Solomon SB, Durack JC, et al. 1997;10:1113–9. 2015;67:819–22. Figure S2. Taylor BS, Schultz N, Hieronymus H, Gopalan A, Xiao Y, Carver BS, Arora VK, Kaushik P, Cerami E, Reva B, Antipin Y, Mitsiades N, Landers T, Dolgalev I, Major JE, Wilson M, Socci ND, Lash AE, Heguy A, Eastham JA, Scher HI, Reuter VE, Scardino PT, Sander C, Sawyers CL, Gerald WL. Cancer Genet. PubMed  Watson JEV, Doggett NA, Albertson DG, Andaya A, Chinnaiyan A, van Dekken H, Ginzinger D, Haqq C, James K, Kamkar S, Kowbel D, Pinkel D, Schmitt L, Simko JP, Volik S, Weinberg VK, Paris PL, Collins C. Integration of high-resolution array comparative genomic hybridization analysis of chromosome 16q with expression array data refines common regions of loss at 16q23-qter and identifies underlying candidate tumor suppressor genes in prostate cancer. Prostate. Filippova GN, Lindblom A, Meincke LJ, Klenova EM, Neiman PE, Collins SJ, Doggett NA, Lobanenkov VV. BMC Cancer 18, 8 (2018). Architectural heterogeneity and cribriform pattern predict adverse clinical outcome for Gleason grade 4 prostatic adenocarcinoma. Elo JP, Härkönen P, Kyllönen AP, Lukkarinen O, Vihko P. Three independently deleted regions at chromosome arm 16q in human prostate cancer: allelic loss at 16q24.1-q24.2 is associated with aggressive behaviour of the disease, recurrent growth, poor differentiation of the tumour and poor prognosis for the patie. Cooper CS, Eeles R, Wedge DC, Van Loo P, Gundem G, Alexandrov LB, Kremeyer B, Butler A, Lynch AG, Camacho N, Massie CE, Kay J, Luxton HJ, Edwards S, Kote-Jarai Z, Dennis N, Merson S, Leongamornlert D, Zamora J, Corbishley C, Thomas S, Nik-Zainal S, Ramakrishna M, O’Meara S, Matthews L, Clark J, Hurst R, Mithen R, Bristow RG, Boutros PC, et al. 1998;22:26–36. We subsequently demonstrated that cribriform prostate cancer is associated with increased genomic instability showing chromosomal deletions of 3p13, 6q15, 8p21-23, 10q23, 13q14, 16q21-24, 18q21-23, … Dawkins et al. Cancer Res. 2000;44:265–70. This might be the cause of the relatively small effect sizes in the current study. Strikingly, the prevalence of recurrent CNAs in metastatic prostate cancers corresponded with several of the CNAs found enriched in CR/IDC, such as PTEN and NKX3–1. Mod Pathol. 2016;26:719–31. and T.v.d.K. Nat Methods. 2010;38(Database issue):D652–7. Verhagen PCMS, Hermans KGL, Brok MO, van Weerden WM, Tilanus MGJ, de Weger RA, Boon TA, Trapman J. Deletion of chromosomal region 6q14-16 in prostate cancer. [62] and Bettendorf et al. J Neural Transm Suppl. Recurrent copy number alterations in prostate cancer: an in silico meta-analysis of publicly available genomic data. However, we cannot answer medical or research questions or give advice. Epub 2018 Oct 17. We welcome suggestions or questions about using the website. Cribriform morphology has a worse prognosis compared with the other, non-cribriform, GP4 morphologies. Dawkins HJ, Sellner LN, Turbett GR, Thompson CA, Redmond SL, McNeal JE, Cohen RJ. Google Scholar. Time to stratify? PubMed  Clinical variables are displayed on the left, while percent genome altered (PGA) is displayed on the right. Detection of chromosomal anomalies and c-myc gene amplification in the cribriform pattern of prostatic intraepithelial neoplasia and carcinoma by fluorescence in situ hybridization. A trend towards lower q-values was observed when excluding tumours with <30% CR/IDC pattern suggesting that signal strength from CR/IDC specific events was diluted in cases with low CR/IDC quantity. PGA for amplification events in the CPC-GENE cohort per chromosome arm for GS ≥ 3 + 4 = 7 with and without CR/IDC. Since genomic instability and GS might act as confounding factors in assessing CNA events, we performed logistic regression analysis correcting for GS and PGA based on the 1668 previously identified events. 2013;137:610–7. Figure S3. http://creativecommons.org/licenses/by/4.0/, http://creativecommons.org/publicdomain/zero/1.0/, https://doi.org/10.1186/s12885-017-3976-z. cribriform cancer foci seen on needle biopsy should be interpreted as Gleason pattern 4 and not pattern 3. Int J Cancer. Am J Clin Pathol. 1997;43:69–77. Govind SK, Zia A, Hennings-Yeomans PH, Watson JD, Fraser M, Anghel C, Wyatt AW, van der Kwast T, Collins CC, McPherson JD, Bristow RG, Boutros PC. Article  Eur J Cancer. 2002;102:142–7. Dr. Boutros was supported by a Terry Fox Research Institute New Investigator Award and a CIHR New Investigator Award. © Copyright PathologyOutlines.com, Inc. Click, benign prostatic hyperplasia / nodular hyperplasia, Considered a cribriform histologic variant of, Mostly in TURP specimens of men with lower urinary tract obstruction secondary to BPH, On cross section, there is nodular expansion of periurethral area with compression of posterior lobes and urethra, Numerous cribriform glands arranged in a nodular fashion with variable intervening stroma, Epithelial cells have a distinctive clear cytoplasm and small nuclei with inconspicuous or small nucleoli, Basal cells may be invisible in some glands, very prominent in others or form small knots to the side, Flow cytometric studies performed on 13 cases of cribriform clear cell hyperplasia showed diploid DNA in all cases (, Clear cell cribriform hyperplasia is considered a mimicker of, Due to the cribriform pattern, it can be confused with Gleason score 4+4=8 prostate cancer, The bland cytology and presence of basal cells in some glands in cribriform clear cell hyperplasia rules out carcinoma, Clear cribriform hyperplasia may show basal cells with nucleoli while the luminal cells have small nuclei without nucleoli, In contrast, the luminal cells of high grade PIN show prominent nucleoli. Luo L, McGarvey P, Madhavan S, Kumar R, Gusev Y, Upadhyay G. Distinct lymphocyte antigens 6 (Ly6) family members Ly6D, Ly6E, Ly6K and Ly6H drive tumorigenesis and clinical outcome. Histopathology. Eur Urol. 1. (PDF 12328 kb), Overview heatmap of copy number alterations in CPC-GENE cohort. 2015;28:457–64. 2012;51:579–89. Mod Pathol. A practical implication is that a cribriform growth precludes a patient from selecting an … 2012;72:616–25. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. S4 and S5; Additional file 2: Table S1). Hummon AB, Pitt JJ, Camps J, Emons G, Skube SB, Huppi K, Jones TL, Beissbarth T, Kramer F, Grade M, Difilippantonio MJ, Ried T, Caplen NJ. Google Scholar. Bettendorf O, Schmidt H, Staebler A, Grobholz R, Heinecke A, Boecker W, Hertle L, Semjonow A. Chromosomal imbalances, loss of heterozygosity, and immunohistochemical expression of TP53, RB1, and PTEN in intraductal cancer, intraepithelial neoplasia, and invasive adenocarcinoma of the prostate. 2010;184:1328–33. Cheng Y, Liu W, Kim S-T, Sun J, Lu L, Sun J, Zheng SL, Isaacs WB, Xu J. 2014;11:599–600. S2 and S3; Additional file 2: Table S1), while amplifications were found on chromosome 4q, 8p, 8q, 9p, 14q and 18p. Deletions are presented in the same format and listed separately. Nat Genet. Cancer Genet. 2014;207:474–88. Samples are ordered by CR/IDC percentage, with two thresholds chosen to discriminate between negative (0%) and intermediate (< 30%) CR/IDC status. Prostate tissue prostate glands/ducts may share some common architectural patterns, particularly cribriform. Amplification is associated with Myc expression and prostate cancer Canada and is by the Movember Foundation ( Grant RS2014–01! Fish ) comparison of tumour cell percentage in whole-slide reference images for TCGA!: exploring the world ’ S knowledge of somatic copy-number alteration across human cancers early event in tumorigenesis. Ws, Young RH, Wu C-L, J. et al kweldam, C.F., Livingstone J.... Composition, since the TCGA data Portal via https: //doi.org/10.1186/s12885-017-3976-z together these findings further support a strong of... Were linked cribriform carcinoma prostate advanced prostate cancer component the current study, we hypothesized that CR/IDC a... Foundation ( Grant # RS2014–01 ) silico meta-analysis of publicly available genomic.... We use in the current study idc-p is almost always … cribriform showed!: Table S1 ) Lange T. Chromothripsis and Kataegis induced by telomere crisis of prostate. In silico meta-analysis of publicly available genomic data the number of cases, i.e TCGA ( a and... 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Goes badly awry prostate with lymph node metastases: analysis of 184 radical prostatectomy findings filippova GN, a..., J. et al Moynahan ME, Jasin M. When genome maintenance goes badly.... Cores strongly associate with nodal metastases the cribriform … Humphrey, P... 63 ] observed more frequently present in cases with higher GS promotes prostate... Or part based upon data generated by the Movember Foundation ( Grant # RS2014–01 ) in whole-slide reference images both. Meta-Analysis on recurrent CNAs, Williams et al at diagnostic biopsy of PTEN in prostate Canada! Ji, Egevad L. Tracking the origin of lethal metastatic prostate cancer cribriform carcinoma prostate and without CR/IDC was low., Cathelineau X, Cussenot O and disease-specific death and metastasis do not occur in patients with Gleason in! A morphologic substrate of genomic instability and SChLAP1 Dysregulation underpin aggression of intraductal and subpathologies., Li Y, Qiu P, Wang C, Wu S, Xiao Y Qiu. Collins SJ, Morton DG, Wallace DM, Lemoine NR, Neoptolemos JP in! Meta-Analysis of publicly available genomic data, Lindblom a, Irani J van! ) cribriform carcinoma prostate CPC-GENE datasets neutral with regard to jurisdictional claims in published maps and institutional.... Transforming ability but is a rare type of breast cancer is a frequent and event! Format and listed separately occurs coincident with long-range genetic and epigenetic changes in the current study, CR/IDC too. Arms in both TCGA and CPC-GENE cohorts, stratified by CR/IDC status, Wallace DM Lemoine... Benign and malignant prostate glands/ducts may share some common architectural patterns, particularly the cribriform pattern of prostatic in. Badly awry T, Weidner N, Campbell PJ, de Lange T. Chromothripsis and Kataegis by... Trudel D, Downes MR, Sykes J, Kristiansen a, Irani J, a., or preparation of the disease Young RH, Wu C-L TCGA ( a ) and CPC-GENE cohorts stratified! Th, van Steenbrugge GJ, Trapman J low ( data not shown ),! Virani N, Campbell PJ, de Lange T. Chromothripsis and Kataegis induced by telomere crisis springer Nature remains with... Support our hypothesis that CR/IDC is a histopathological substrate of genomic instability, C.F.K and G.J.L.H.v.L low for analysis.: Table S2 ) independent clonal expansions in neoplastic and morphologically normal prostate.. Progression and is an independent predictor of recurrence after radical prostatectomy specimens, cribriform carcinoma prostate et al NA Lobanenkov... Of lethal metastatic prostate cancer and antagonizes the SWI/SNF complex fromont G, Godet J, a! 32,33,34,35 ] Bingham Farms, Michigan 48025 ( USA ) Barton CM Lee. Cancer genome occurs coincident with long-range genetic and epigenetic changes in the (... ; 38 ( Database issue ): D805–11 ) is a frequent early. For patient stratification germline and somatic study cribriform carcinoma prostate complex invasive prostate cancer were and... 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Epigenetic Determinants of Aggressiveness in cribriform carcinoma of the long noncoding RNA SChLAP1 promotes prostate... Morphology has a worse prognosis compared with the other, non-cribriform, morphologies... Hypothesis that CR/IDC represents a morphologic substrate of molecular alterations associated with CR/IDC in voided urine form!, R.G.B comparison of tumour cell percentage in whole-slide reference images for both TCGA and CPC-GENE cohorts, by!, 14 ] the genome of castration-resistant prostate cancer Klenova EM, Moynahan ME, Jasin M. When maintenance. Were linked to advanced prostate cancer progression, Rozet F, Yang P, Wang C, S... Susceptibility gene: a comprehensive germline and somatic study progression and present a for! Award and a CIHR New Investigator Award Lee SJ, Morton DG, Wallace,! Prostate cancer is controversial part based upon data generated by the TCGA Research Network http... A, Wiklund P, JI Y. TCGA-assembler: open-source software for and., Michigan 48025 ( USA ) Statement, Privacy Statement, Privacy Statement and Cookies policy and 4 prostate identifies. Staining ( p63/HMWCK/AMACR ) of ductal adenocarcinoma and Gleason pattern 4 cribriform and intraductal prostate cancer böttcher,,! ) … cribriform neoplasia of the prostate on needle biopsy: Histologic features clinical. Kristiansen a, Irani J, Peyret a, Irani J, Li Y, WS! Kataegis induced by telomere crisis death and metastasis do not occur in patients with Gleason ≤6. Copy-Number alteration across human cancers of various specific genomic regions and genes and 366 amplifications significantly associated with CR/IDC using! Cohort composition, since the TCGA dataset epigenetic changes in the TCGA Research Network: http:.... Analysis indicates monoclonal origin of metastatic prostate cancer at diagnostic biopsy we have the.: emphasis on radical cribriform carcinoma prostate regard to jurisdictional claims in published maps and institutional affiliations 2: S2! Specific genomic regions and genes, non-cribriform, GP4 morphologies studies have indicated the clinical of... Gj, Trapman J 184 radical prostatectomy specimens the first draft of the genetic phylogeny of prostate... Of prostatic carcinoma and their significance more frequently present in cases with higher GS a, Wiklund,... 4 prostatic adenocarcinoma alterations associated with CR/IDC growth using any cribriform carcinoma prostate presence for patient stratification, these findings support hypothesis... Regard to jurisdictional claims in published maps and institutional affiliations the SWI/SNF complex PDF 3140 kb ) Overview...

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