Two types of primary mucinous ovarian tumors can be distinguished based on their origin.
Adenocarcinoma, Mucinous
/ chemistry
Adult
Baltimore
Biomarkers, Tumor
/ analysis
Brenner Tumor
/ chemistry
Cystadenoma, Mucinous
/ chemistry
Databases, Factual
Disease Progression
Female
Gene Dosage
Genetic Predisposition to Disease
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Matrix Attachment Region Binding Proteins
/ analysis
Middle Aged
Mutation
Netherlands
Ovarian Neoplasms
/ chemistry
Phenotype
Proto-Oncogene Proteins c-myc
/ genetics
Proto-Oncogene Proteins p21(ras)
/ genetics
Receptor, ErbB-2
/ genetics
Teratoma
/ chemistry
Transcription Factors
/ analysis
Tumor Suppressor Protein p53
/ genetics
Journal
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
ISSN: 1530-0285
Titre abrégé: Mod Pathol
Pays: United States
ID NLM: 8806605
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
29
08
2019
accepted:
07
10
2019
revised:
07
10
2019
pubmed:
7
11
2019
medline:
26
1
2021
entrez:
8
11
2019
Statut:
ppublish
Résumé
The origin of primary mucinous ovarian tumors is unknown. We explore the hypothesis that they originate from either Brenner tumors or teratomas and examine differences between the tumors that arise in these settings. A total of 104 Brenner tumor-associated mucinous tumors and 58 teratoma-associated mucinous tumors were analyzed. Immunohistochemistry for 21 antigens and fluorescence in situ hybridization for ERBB2 and MYC were performed. Genome-wide copy number analysis and mutation analysis for 56 cancer-related genes was carried out on a subset of mucinous ovarian tumors and their complementary Brenner tumor or teratoma. Patients with teratoma-associated mucinous tumors were significantly younger than patients with Brenner tumor-associated mucinous tumors (43 vs. 61 years). During progression from cystadenoma to atypical proliferative mucinous (borderline) tumor to carcinoma expression of typical gastrointestinal markers was increased in both Brenner tumor-associated and teratoma-associated mucinous tumors. Brenner tumor-associated mucinous tumors showed more frequently calcifications and Walthard cell nests, rarely expressed SATB2 and showed more often co-deletion of CDKN2A and MTAP. Teratoma-associated mucinous tumors were characterized by mucinous stromal dissection, SATB2 expression and RNF43 mutations. Other frequent mutations in both Brenner tumor-associated and teratoma-associated mucinous tumors were TP53 and KRAS mutations. Based on identical mutations or copy number profiles clonal relationships were indicated in two mucinous tumors and their associated Brenner tumor. Teratomas and Brenner tumors give rise to different subtypes of mucinous ovarian tumors. Subsequent progression pathways are comparable since both Brenner tumor-associated and teratoma-associated mucinous tumors develop a gastrointestinal immunophenotype during progression and show early mutations in KRAS and TP53. Teratoma-associated mucinous tumors may more closely resemble true gastrointestinal tumors, indicated by their expression of SATB2 and the presence of RNF43 mutations.
Identifiants
pubmed: 31695154
doi: 10.1038/s41379-019-0401-y
pii: S0893-3952(22)00897-3
doi:
Substances chimiques
Biomarkers, Tumor
0
KRAS protein, human
0
MYC protein, human
0
Matrix Attachment Region Binding Proteins
0
Proto-Oncogene Proteins c-myc
0
SATB2 protein, human
0
TP53 protein, human
0
Transcription Factors
0
Tumor Suppressor Protein p53
0
ERBB2 protein, human
EC 2.7.10.1
Receptor, ErbB-2
EC 2.7.10.1
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Comparative Study
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
722-733Références
Simons M, Massuger L, Bruls J, Bulten J, Teerenstra S, Nagtegaal I. Relatively poor survival of mucinous ovarian carcinoma in advanced stage: a systematic review and meta-analysis. Int J Gynecol Cancer. 2017;27:651–8.
pubmed: 28399027
Kurman RJ, Shih IeM. The dualistic model of ovarian carcinogenesis: revisited, revised, and expanded. Am J Pathol. 2016;186:733–47.
pubmed: 27012190
pmcid: 5808151
Roma AA, Masand RP. Different staining patterns of ovarian Brenner tumor and the associated mucinous tumor. Ann Diagn Pathol. 2015;19:29–32.
pubmed: 25596159
Seidman JD, Khedmati F. Exploring the histogenesis of ovarian mucinous and transitional cell (Brenner) neoplasms and their relationship with Walthard cell nests: a study of 120 tumors. Arch Pathol Lab Med. 2008;132:1753–60.
pubmed: 18976011
Kondi-Pafiti A, Kairi-Vassilatou E, Iavazzo C, Vouza E, Mavrigiannaki P, Kleanthis C, et al. Clinicopathological features and immunoprofile of 30 cases of Brenner ovarian tumors. Arch Gynecol Obstet. 2012;285:1699–702.
pubmed: 22198845
Wang Y, Wu RC, Shwartz LE, Haley L, Lin MT, Shih IeM, et al. Clonality analysis of combined Brenner and mucinous tumours of the ovary reveals their monoclonal origin. J Pathol. 2015;237:146–51.
pubmed: 26095692
pmcid: 4703556
Tafe LJ, Muller KE, Ananda G, Mitchell T, Spotlow V, Patterson SE, et al. Molecular genetic analysis of ovarian brenner tumors and associated mucinous epithelial neoplasms: high variant concordance and identification of mutually exclusive RAS driver mutations and MYC amplification. Am J Pathol. 2016;186:671–7.
pubmed: 26797085
pmcid: 5903309
Deka R, Chakravarti A, Surti U, Hauselman E, Reefer J, Majumder PP, et al. Genetics and biology of human ovarian teratomas. II. Molecular analysis of origin of nondisjunction and gene-centromere mapping of chromosome I markers. Am J Hum Genet. 1990;47:644–55.
pubmed: 1977308
pmcid: 1683806
Surti U, Hoffner L, Chakravarti A, Ferrell RE. Genetics and biology of human ovarian teratomas. I. Cytogenetic analysis and mechanism of origin. Am J Hum Genet. 1990;47:635–43.
pubmed: 2220805
pmcid: 1683780
Vang R, Gown AM, Zhao C, Barry TS, Isacson C, Richardson MS, et al. Ovarian mucinous tumors associated with mature cystic teratomas: morphologic and immunohistochemical analysis identifies a subset of potential teratomatous origin that shares features of lower gastrointestinal tract mucinous tumors more commonly encountered as secondary tumors in the ovary. Am J Surg Pathol. 2007;31:854–69.
pubmed: 17527072
Ronnett BM, Seidman JD. Mucinous tumors arising in ovarian mature cystic teratomas: relationship to the clinical syndrome of pseudomyxoma peritonei. Am J Surg Pathol. 2003;27:650–7.
pubmed: 12717249
McKenney JK, Soslow RA, Longacre TA. Ovarian mature teratomas with mucinous epithelial neoplasms: morphologic heterogeneity and association with pseudomyxoma peritonei. Am J Surg Pathol. 2008;32:645–55.
pubmed: 18344868
Kerr SE, Flotte AB, McFalls MJ, Vrana JA, Halling KC, Bell DA. Matching maternal isodisomy in mucinous carcinomas and associated ovarian teratomas provides evidence of germ cell derivation for some mucinous ovarian tumors. Am J Surg Pathol. 2013;37:1229–35.
pubmed: 23774174
Fujii K, Yamashita Y, Yamamoto T, Takahashi K, Hashimoto K, Miyata T, et al. Ovarian mucinous tumors arising from mature cystic teratomas-a molecular genetic approach for understanding the cellular origin. Hum Pathol. 2014;45:717–24.
pubmed: 24485845
Snir OL, Buza N, Hui P. Mucinous epithelial tumours arising from ovarian mature teratomas: a tissue genotyping study. Histopathology. 2016;69:383–92.
pubmed: 26952875
Ryland GL, Hunter SM, Doyle MA, Caramia F, Li J, Rowley SM, et al. Mutational landscape of mucinous ovarian carcinoma and its neoplastic precursors. Genome Med. 2015;7:87.
pubmed: 26257827
pmcid: 4528310
Mackenzie R, Kommoss S, Winterhoff BJ, Kipp BR, Garcia JJ, Voss J, et al. Targeted deep sequencing of mucinous ovarian tumors reveals multiple overlapping RAS-pathway activating mutations in borderline and cancerous neoplasms. BMC Cancer. 2015;15:415.
pubmed: 25986173
pmcid: 4494777
Casparie M, Tiebosch AT, Burger G, Blauwgeers H, van de Pol A, van Krieken JH, et al. Pathology databanking and biobanking in The Netherlands, a central role for PALGA, the nationwide histopathology and cytopathology data network and archive. Cell Oncol. 2007;29:19–24.
pubmed: 17429138
pmcid: 4618410
Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol. 2013;31:3997–4013.
pubmed: 24101045
Scheinin I, Sie D, Bengtsson H, van de Wiel MA, Olshen AB, van Thuijl HF, et al. DNA copy number analysis of fresh and formalin-fixed specimens by shallow whole-genome sequencing with identification and exclusion of problematic regions in the genome assembly. Genome Res. 2014;24:2022–32.
pubmed: 25236618
pmcid: 4248318
van de Wiel MA, Brosens R, Eilers PH, Kumps C, Meijer GA, Menten B, et al. Smoothing waves in array CGH tumor profiles. Bioinformatics. 2009;25:1099–104.
pubmed: 19276148
Eijkelenboom A, Kamping EJ, Kastner-van Raaij AW, Hendriks-Cornelissen SJ, Neveling K, Kuiper RP, et al. Reliable next-generation sequencing of formalin-fixed, paraffin-embedded tissue using single molecule tags. J Mol Diagn. 2016;18:851–63.
pubmed: 27637301
O’Roak BJ, Vives L, Fu W, Egertson JD, Stanaway IB, Phelps IG, et al. Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders. Science. 2012;338:1619–22.
pubmed: 23160955
pmcid: 3528801
Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature. 2016;536:285.
pubmed: 27535533
pmcid: 5018207
Ostrovnaya I, Olshen AB, Seshan VE, Orlow I, Albertson DG, Begg CB. A metastasis or a second independent cancer? Evaluating the clonal origin of tumors using array copy number data. Stat Med. 2010;29:1608–21.
pubmed: 20205270
pmcid: 3145177
Olshen AB, Venkatraman ES, Lucito R, Wigler M. Circular binary segmentation for the analysis of array-based DNA copy number data. Biostatistics. 2004;5:557–72.
pubmed: 15475419
van de Wiel MA, Kim KI, Vosse SJ, van Wieringen WN, Wilting SM, Ylstra B. CGHcall: calling aberrations for array CGH tumor profiles. Bioinformatics. 2007;23:892–4.
pubmed: 17267432
van de Wiel MA, Wieringen WN. CGHregions: dimension reduction for array CGH data with minimal information loss. Cancer Inf. 2007;3:55–63.
Gorringe KL, Jacobs S, Thompson ER, Sridhar A, Qiu W, Choong DY, et al. High-resolution single nucleotide polymorphism array analysis of epithelial ovarian cancer reveals numerous microdeletions and amplifications. Clin Cancer Res. 2007;13:4731–9.
pubmed: 17699850
Haverty PM, Hon LS, Kaminker JS, Chant J, Zhang Z. High-resolution analysis of copy number alterations and associated expression changes in ovarian tumors. BMC Med Genomics. 2009;2:21.
pubmed: 19419571
pmcid: 2694826
Huang RY, Chen GB, Matsumura N, Lai HC, Mori S, Li J, et al. Histotype-specific copy-number alterations in ovarian cancer. BMC Med Genomics. 2012;5:47.
pubmed: 23078675
pmcid: 3567940
Cancer Genome Atlas N. Comprehensive molecular characterization of human colon and rectal cancer. Nature. 2012;487:330–7.
Rechsteiner M, Zimmermann AK, Wild PJ, Caduff R, von Teichman A, Fink D, et al. TP53 mutations are common in all subtypes of epithelial ovarian cancer and occur concomitantly with KRAS mutations in the mucinous type. Exp Mol Pathol. 2013;95:235–41.
pubmed: 23965232
Hunter SM, Gorringe KL, Christie M, Rowley SM, Bowtell DD, Australian Ovarian Cancer Study G, et al. Pre-invasive ovarian mucinous tumors are characterized by CDKN2A and RAS pathway aberrations. Clin Cancer Res. 2012;18:5267–77.
pubmed: 22891197
Perez Montiel D, Arispe Angulo K, Cantu-de Leon D, Bornstein Quevedo L, Chanona Vilchis J, Herrera Montalvo L. The value of SATB2 in the differential diagnosis of intestinal-type mucinous tumors of the ovary: primary vs metastatic. Ann Diagn Pathol. 2015;19:249–52.
pubmed: 26059401
Moh M, Krings G, Ates D, Aysal A, Kim GE, Rabban JT. SATB2 expression distinguishes ovarian metastases of colorectal and appendiceal origin from primary ovarian tumors of mucinous or endometrioid type. Am J Surg Pathol. 2016;40:419–32.
pubmed: 26551622
Giannakis M, Hodis E, Jasmine Mu X, Yamauchi M, Rosenbluh J, Cibulskis K. et al. RNF43 is frequently mutated in colorectal and endometrial cancers. Nat Genet. 2014;46:1264–6.
pubmed: 25344691
pmcid: 4283570
Ryland GL, Hunter SM, Doyle MA, Rowley SM, Christie M, Allan PE, et al. RNF43 is a tumour suppressor gene mutated in mucinous tumours of the ovary. J Pathol. 2013;229:469–76.
pubmed: 23096461
Gorringe KL, Ramakrishna M, Williams LH, Sridhar A, Boyle SE, Bearfoot JL, et al. Are there any more ovarian tumor suppressor genes? A new perspective using ultra high-resolution copy number and loss of heterozygosity analysis. Genes Chromosomes Cancer. 2009;48:931–42.
pubmed: 19603523
Powell EL, Leoni LM, Canto MI, Forastiere AA, Iocobuzio-Donahue CA, Wang JS, et al. Concordant loss of MTAP and p16/CDKN2A expression in gastroesophageal carcinogenesis: evidence of homozygous deletion in esophageal noninvasive precursor lesions and therapeutic implications. Am J Surg Pathol. 2005;29:1497–504.
pubmed: 16224217
Krasinskas AM, Bartlett DL, Cieply K, Dacic S. CDKN2A and MTAP deletions in peritoneal mesotheliomas are correlated with loss of p16 protein expression and poor survival. Mod Pathol. 2010;23:531–8.
pubmed: 20081810
Bishop DT, Demenais F, Iles MM, Harland M, Taylor JC, Corda E, et al. Genome-wide association study identifies three loci associated with melanoma risk. Nat Genet. 2009;41:920–5.
pubmed: 19578364
pmcid: 2741419
Christopher SA, Diegelman P, Porter CW, Kruger WD. Methylthioadenosine phosphorylase, a gene frequently codeleted with p16(cdkN2a/ARF), acts as a tumor suppressor in a breast cancer cell line. Cancer Res. 2002;62:6639–44.
pubmed: 12438261
Bertino JR, Waud WR, Parker WB, Lubin M. Targeting tumors that lack methylthioadenosine phosphorylase (MTAP) activity: current strategies. Cancer Biol Ther. 2011;11:627–32.
pubmed: 21301207
pmcid: 3084968
Strickland S, Wasserman JK, Giassi A, Djordjevic B, Parra-Herran C. Immunohistochemistry in the diagnosis of mucinous neoplasms involving the ovary: the added value of SATB2 and biomarker discovery through protein expression database mining. Int J Gynecol Pathol. 2016;35:191–208.
pubmed: 26535987
Chu PG, Chung L, Weiss LM, Lau SK. Determining the site of origin of mucinous adenocarcinoma: an immunohistochemical study of 175 cases. Am J Surg Pathol. 2011;35:1830–6.
pubmed: 21881489