A four-antibody immunohistochemical panel can distinguish clinico-pathological clusters of urothelial carcinoma and reveals high concordance between primary tumor and lymph node metastases.
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor
/ metabolism
Carcinoma, Transitional Cell
/ diagnosis
Case-Control Studies
Feasibility Studies
Female
Humans
Immunohistochemistry
Lymph Nodes
/ pathology
Lymphatic Metastasis
Male
Middle Aged
Prognosis
Retrospective Studies
Urinary Bladder Neoplasms
/ diagnosis
Bladder cancer
Immunohistochemistry
Lymph node metastases
Molecular classification
Subtype profiling
Urothelial carcinoma
Journal
Virchows Archiv : an international journal of pathology
ISSN: 1432-2307
Titre abrégé: Virchows Arch
Pays: Germany
ID NLM: 9423843
Informations de publication
Date de publication:
Apr 2021
Apr 2021
Historique:
received:
26
06
2020
accepted:
14
10
2020
revised:
08
10
2020
pubmed:
1
11
2020
medline:
7
4
2021
entrez:
31
10
2020
Statut:
ppublish
Résumé
Urothelial carcinoma of the bladder (UC) has a poor prognosis, partly because of chemotherapy resistance. Molecular classifications have shown their interest and can help to offer personalized treatment. In this study, we evaluated the feasibility of an immunohistochemical study to divide advanced UC into clinico-pathological-molecular subgroups and evaluate phenotypic correspondence between primary UC and matched lymph node metastases (LMN). An eight-antibody immunohistochemical panel was performed on UC and matched LMN from patients treated with radical cystectomy. One hundred eighty-seven UCs (100 pN0 tumor and 87 pN+ tumor) were tested. Multiple correspondence analysis showed that UC expressing GATA3 also expressed FOXA1 (p = 0.010) and did not stain for CK5/6 (p = 0.031) nor CK14 (p = 0.003). UC expressing CK14 coexpressed CK5/6 (p < 0.0001), had high Ki67 (p = 0.010) and no GATA3 (p = 0.003) nor FOXA1 (p = 0.011) expression. Loss of expression of STAG2 was associated with high Ki67 (p = 0.001). Sixty-seven percent of [CK5/6 CK14]+ [GATA3 FOAXA1]- patients had high Ki67 expression vs 37% of [GATA3 FOXA1]+ [CK5/6 CK14]- patients (p = 0.024). The majority of [CK5/6 CK14]+ [GATA3 FOAXA1]- patients (92%) had advanced disease (pT3-pT4) whilst 86% of pT1-T2 cases were [GATA3 FOXA1]+ [CK5/6 CK14]- (p = 0.041). Differential antigen expression between 63 pN+ primary tumors and their corresponding LNM showed the following concordance percentages: p53 (76%), p63 (75%), CK5/6 (65%), CK14 (89%), GATA3 (75%), FOXA1 (68%), STAG2 (65%), and Ki-67 (71%). These results support the interest of immunohistochemistry for subtype profiling in metastatic UC, using CK5/6, CK14, GATA3, and FOXA1, highlighting also few phenotypical modifications when tumor spreads to lymph nodes.
Identifiants
pubmed: 33128085
doi: 10.1007/s00428-020-02951-0
pii: 10.1007/s00428-020-02951-0
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
637-645Références
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424. https://doi.org/10.3322/caac.21492
doi: 10.3322/caac.21492
pubmed: 30207593
pmcid: 30207593
Sanli O, Dobruch J, Knowles MA, Burger M, Alemozaffar M, Nielsen ME, Lotan Y (2017) Bladder cancer. Nat Rev Dis Prim 3:1–19. https://doi.org/10.1038/nrdp.2017.22
doi: 10.1038/nrdp.2017.22
Griffiths G (2011) International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 trial. J Clin Oncol 29:2171–2177. https://doi.org/10.1200/JCO.2010.32.3139
doi: 10.1200/JCO.2010.32.3139
pubmed: 21502557
Sjödahl G, Lövgren K, Lauss M, Patschan O, Gudjonsson S, Chebil G, Aine M, Eriksson P, Månsson W, Lindgren D, Fernö M, Liedberg F, Höglund M (2013) Toward a molecular pathologic classification of urothelial carcinoma. Am J Pathol 183:681–691. https://doi.org/10.1016/j.ajpath.2013.05.013
doi: 10.1016/j.ajpath.2013.05.013
pubmed: 23827819
Choi W, Ochoa A, McConkey DJ et al (2017) Genetic alterations in the molecular subtypes of bladder cancer: illustration in the cancer genome atlas dataset. Eur Urol 72:354–365
doi: 10.1016/j.eururo.2017.03.010
Thomsen MBH, Nordentoft I, Lamy P, Vang S, Reinert L, Mapendano CK, Høyer S, Ørntoft TF, Jensen JB, Dyrskjøt L (2017) Comprehensive multiregional analysis of molecular heterogeneity in bladder cancer. Sci Rep 7:11702. https://doi.org/10.1038/s41598-017-11291-0
doi: 10.1038/s41598-017-11291-0
pubmed: 28916750
pmcid: 5600970
Faltas BM, Prandi D, Tagawa ST, Molina AM, Nanus DM, Sternberg C, Rosenberg J, Mosquera JM, Robinson B, Elemento O, Sboner A, Beltran H, Demichelis F, Rubin MA (2016) Clonal evolution of chemotherapy-resistant urothelial carcinoma. Nat Genet 48:1490–1499. https://doi.org/10.1038/ng.3692
doi: 10.1038/ng.3692
pubmed: 27749842
pmcid: 5549141
Choi W, Porten S, Kim S, Willis D, Plimack ER, Hoffman-Censits J, Roth B, Cheng T, Tran M, Lee IL, Melquist J, Bondaruk J, Majewski T, Zhang S, Pretzsch S, Baggerly K, Siefker-Radtke A, Czerniak B, Dinney CPN, McConkey DJ (2014) Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy. Cancer Cell 25:152–165. https://doi.org/10.1016/j.ccr.2014.01.009
doi: 10.1016/j.ccr.2014.01.009
pubmed: 24525232
pmcid: 4011497
Baras AS, Gandhi N, Munari E, Faraj S, Shultz L, Marchionni L, Schoenberg M, Hahn N, Hoque M, Berman D, Bivalacqua TJ, Netto G (2015) Identification and validation of protein biomarkers of response to neoadjuvant platinum chemotherapy in muscle invasive urothelial carcinoma. PLoS One 10:1–11. https://doi.org/10.1371/journal.pone.0131245
doi: 10.1371/journal.pone.0131245
Groenendijk FH, De Jong J, Fransen Van De Putte EE et al (2016) ERBB2 mutations characterize a subgroup of muscle-invasive bladder cancers with excellent response to neoadjuvant chemotherapy. Eur Urol 69:384–388. https://doi.org/10.1016/j.eururo.2015.01.014
doi: 10.1016/j.eururo.2015.01.014
pubmed: 25636205
Hurst CD, Alder O, Platt FM et al (2017) Genomic subtypes of non-invasive bladder cancer with distinct metabolic profile and female gender Bias in KDM6A mutation frequency. Cancer Cell 32:701–715.e7. https://doi.org/10.1016/j.ccell.2017.08.005
doi: 10.1016/j.ccell.2017.08.005
pubmed: 29136510
pmcid: 5774674
Seiler R, Ashab HAD, Erho N, van Rhijn BWG, Winters B, Douglas J, van Kessel KE, Fransen van de Putte EE, Sommerlad M, Wang NQ, Choeurng V, Gibb EA, Palmer-Aronsten B, Lam LL, Buerki C, Davicioni E, Sjödahl G, Kardos J, Hoadley KA, Lerner SP, McConkey DJ, Choi W, Kim WY, Kiss B, Thalmann GN, Todenhöfer T, Crabb SJ, North S, Zwarthoff EC, Boormans JL, Wright J, Dall’Era M, van der Heijden MS, Black PC (2017) Impact of molecular subtypes in muscle-invasive bladder cancer on predicting response and survival after neoadjuvant chemotherapy. Eur Urol 72:544–554. https://doi.org/10.1016/j.eururo.2017.03.030
doi: 10.1016/j.eururo.2017.03.030
pubmed: 28390739
Aine M, Eriksson P, Liedberg F, Sjödahl G, Höglund M (2015) Biological determinants of bladder cancer gene expression subtypes. Sci Rep 5:1–13. https://doi.org/10.1038/srep10957
doi: 10.1038/srep10957
Yatabe Y, Dacic S, Borczuk AC, Warth A, Russell PA, Lantuejoul S, Beasley MB, Thunnissen E, Pelosi G, Rekhtman N, Bubendorf L, Mino-Kenudson M, Yoshida A, Geisinger KR, Noguchi M, Chirieac LR, Bolting J, Chung JH, Chou TY, Chen G, Poleri C, Lopez-Rios F, Papotti M, Sholl LM, Roden AC, Travis WD, Hirsch FR, Kerr KM, Tsao MS, Nicholson AG, Wistuba I, Moreira AL (2019) Best practices recommendations for diagnostic immunohistochemistry in lung cancer. J Thorac Oncol 14:377–407. https://doi.org/10.1016/j.jtho.2018.12.005
doi: 10.1016/j.jtho.2018.12.005
pubmed: 30572031
Jones TD, Carr MD, Eble JN, Wang M, Lopez-Beltran A, Cheng L (2005) Clonal origin of lymph node metastases in bladder carcinoma. Cancer 104:1901–1910. https://doi.org/10.1002/cncr.21466
doi: 10.1002/cncr.21466
pubmed: 16196038
Sjödahl G, Eriksson P, Lövgren K, Marzouka NAD, Bernardo C, Nordentoft I, Dyrskjøt L, Liedberg F, Höglund M (2018) Discordant molecular subtype classification in the basal-squamous subtype of bladder tumors and matched lymph-node metastases. Mod Pathol An Off J United States Can Acad Pathol Inc 31:1869–1881. https://doi.org/10.1038/s41379-018-0096-5
doi: 10.1038/s41379-018-0096-5
Jourdan F, Sebbagh N, Comperat E, Mourra N, Flahault A, Olschwang S, Duval A, Hamelin R, Flejou JF (2003) Tissue microarray technology: validation in colorectal carcinoma and analysis of p53, hMLH1, and hMSH2 immunohistochemical expression. Virchows Arch An Int J Pathol 443:115–121. https://doi.org/10.1007/s00428-003-0833-z
doi: 10.1007/s00428-003-0833-z
Sjödahl G (2018) Molecular subtype profiling of urothelial carcinoma using a subtype-specific immunohistochemistry panel. In: Methods in Molecular Biology. Humana Press Inc, pp 53–64
Kamoun A, de Reyniès A, Allory Y, Sjödahl G, Robertson AG, Seiler R, Hoadley KA, Groeneveld CS, Al-Ahmadie H, Choi W, Castro MAA, Fontugne J, Eriksson P, Mo Q, Kardos J, Zlotta A, Hartmann A, Dinney CP, Bellmunt J, Powles T, Malats N, Chan KS, Kim WY, McConkey DJ, Black PC, Dyrskjøt L, Höglund M, Lerner SP, Real FX, Radvanyi F (2020) Bladder Cancer Molecular Taxonomy Group.Eur Urol 77(4):420-433. https://doi.org/10.1016/j.eururo.2019.09.006
Sjödahl G, Lauss M, Lövgren K et al (2012) A molecular taxonomy for urothelial carcinoma. Clin Cancer Res 18:3377–3386. https://doi.org/10.1158/1078-0432.CCR-12-0077-T
doi: 10.1158/1078-0432.CCR-12-0077-T
pubmed: 22553347
Robertson AG, Kim J, Al-Ahmadie H et al (2017) Comprehensive molecular characterization of muscle-invasive bladder cancer. Cell 171:540–556.e25. https://doi.org/10.1016/j.cell.2017.09.007
doi: 10.1016/j.cell.2017.09.007
pubmed: 28988769
pmcid: 5687509
Rebouissou S, Bernard-Pierrot I, De Reyniès A et al (2014) EGFR as a potential therapeutic target for a subset of muscle-invasive bladder cancers presenting a basal-like phenotype. Sci Transl Med 6:244ra91. https://doi.org/10.1126/scitranslmed.3008970
doi: 10.1126/scitranslmed.3008970
pubmed: 25009231
Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A, Dawson N, O'Donnell PH, Balmanoukian A, Loriot Y, Srinivas S, Retz MM, Grivas P, Joseph RW, Galsky MD, Fleming MT, Petrylak DP, Perez-Gracia JL, Burris HA, Castellano D, Canil C, Bellmunt J, Bajorin D, Nickles D, Bourgon R, Frampton GM, Cui N, Mariathasan S, Abidoye O, Fine GD, Dreicer R (2016) Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet 387:1909–1920. https://doi.org/10.1016/S0140-6736(16)00561-4
doi: 10.1016/S0140-6736(16)00561-4
pubmed: 26952546
pmcid: 5480242
Warrick JI, Walter V, Yamashita H, Chung E, Shuman L, Amponsa VO, Zheng Z, Chan W, Whitcomb TL, Yue F, Iyyanki T, Kawasawa YI, Kaag M, Guo W, Raman JD, Park JS, DeGraff DJ (2016) FOXA1, GATA3 and PPARIγ Cooperate to drive luminal subtype in bladder cancer: a molecular analysis of established human cell lines. Sci Rep 6:1–15. https://doi.org/10.1038/srep38531
doi: 10.1038/srep38531
Lopez-Beltran A, Henriques V, Montironi R, Cimadamore A, Raspollini MR, Cheng L (2019) Variants and new entities of bladder cancer. Histopathology 74:77–96. https://doi.org/10.1111/his.13752
doi: 10.1111/his.13752
pubmed: 30565299
Rebola J, Aguiar P, Blanca A, Montironi R, Cimadamore A, Cheng L, Henriques V, Lobato-Faria P, Lopez-Beltran A (2019) Predicting outcomes in non-muscle invasive (Ta/T1) bladder cancer: the role of molecular grade based on luminal/basal phenotype. Virchows Arch 475:445–455. https://doi.org/10.1007/s00428-019-02593-x
doi: 10.1007/s00428-019-02593-x
pubmed: 31240474
Ottley EC, Pell R, Brazier B, Hollidge J, Kartsonaki C, Browning L, O'Neill E, Kiltie AE (2020) Greater utility of molecular subtype rather than epithelial-to- mesenchymal transition (EMT) markers for prognosis in high-risk non-muscle-invasive (HGT1) bladder cancer. J Pathol Clin Res. https://doi.org/10.1002/cjp2.167
Qiao Y, Zhu X, Li A, Yang S, Zhang J (2016) Complete loss of STAG2 expression is an indicator of good prognosis in patients with bladder cancer. Tumor Biol 37:10279–10286. https://doi.org/10.1007/s13277-016-4894-4
doi: 10.1007/s13277-016-4894-4
Solomon DA, Kim J, Bondaruk J et al (2014) Frequent truncating mutations of STAG2 in bladder cancer. Nat Genet 45:1428–1430. https://doi.org/10.1038/ng.2800
doi: 10.1038/ng.2800
Taylor CF, Platt FM, Hurst CD, Thygesen HH, Knowles MA (2014) Frequent inactivating mutations of STAG2 in bladder cancer are associated with low tumour grade and stage and inversely related to chromosomal copy number changes. Hum Mol Genet 23:1964–1974. https://doi.org/10.1093/hmg/ddt589
doi: 10.1093/hmg/ddt589
pubmed: 24270882
Lelo A, Prip F, Harris BT, Solomon D, Berry DL, Chaldekas K, Kumar A, Simko J, Jensen JB, Bhattacharyya P, Mannion C, Kim JS, Philips G, Dyrskjøt L, Waldman T (2018) STAG2 is a biomarker for prediction of recurrence and progression in papillary non – muscle-invasive bladder. Cancer. 1–10:4145–4153. https://doi.org/10.1158/1078-0432.CCR-17-3244
doi: 10.1158/1078-0432.CCR-17-3244
Miyakawa J, Morikawa T, Miyama Y, Nakagawa T, Kawai T, Homma Y, Fukayama M (2017) Loss of stromal antigen 2 (STAG2) expression in upper urinary tract carcinoma: differential prognostic effect according to the Ki-67 proliferating index. Ann Surg Oncol 24:4059–4066. https://doi.org/10.1245/s10434-017-6097-7
doi: 10.1245/s10434-017-6097-7
pubmed: 28967037
Seiler R, Gibb EA, Wang NQ, Oo HZ, Lam HM, van Kessel KE, Voskuilen CS, Winters B, Erho N, Takhar MM, Douglas J, Vakar-Lopez F, Crabb SJ, van Rhijn BWG, Fransen van de Putte EE, Zwarthoff EC, Thalmann GN, Davicioni E, Boormans JL, Dall'Era M, van der Heijden MS, Wright JL, Black PC (2019) Divergent biological response to neoadjuvant chemotherapy in muscle-invasive bladder cancer. Clin Cancer Res 25:5082–5093. https://doi.org/10.1158/1078-0432.CCR-18-1106
doi: 10.1158/1078-0432.CCR-18-1106
pubmed: 30224344
Marzouka NAD, Eriksson P, Rovira C, Liedberg F, Sjödahl G, Höglund M (2018) A validation and extended description of the Lund taxonomy for urothelial carcinoma using the TCGA cohort. Sci Rep 8. https://doi.org/10.1038/s41598-018-22126-x
Rodriguez Pena MDC, Chaux A, Eich ML, Tregnago AC, Taheri D, Borhan W, Sharma R, Rezaei MK, Netto GJ (2019) Immunohistochemical assessment of basal and luminal markers in non-muscle invasive urothelial carcinoma of bladder. Virchows Arch 475:349–356. https://doi.org/10.1007/s00428-019-02618-5
doi: 10.1007/s00428-019-02618-5
pubmed: 31300876