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Revisiones en Cáncer 00082 / http://dx.doi.org/10.20960/revcancer.00082

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Carcinomas de ovario: características clínico-patológicas y moleculares. Comentarios sobre la estadificación FIGO 2014

Jaime Prat, Emanuela D´Angelo, Íñigo Espinosa

Prepublicado: 2024-11-08

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Según el tipo celular y las alteraciones genéticas se distinguen cinco tipos principales de carcinoma de ovario que, en conjunto, representan más del 95 % del total. Por orden de frecuencia son: a) carcinomas serosos de alto grado (70 %); b) carcinomas endometrioides (10 %); c) carcinomas de células claras (10 %); d) carcinomas mucinosos (3-4 %); y e) carcinomas serosos de bajo grado (< 5 %). Se trata de 5 enfermedades distintas que difieren notablemente en cuanto al pronóstico y tratamiento. En esta revisión se destacan los recientes avances en patología y genética molecular que, no solo han permitido conocer mejor la patogenia de estos cánceres, sino también han contribuido a mejorar notablemente el tratamiento de las pacientes. Asimismo, se reevalúa la estadificación FIGO que propusimos hace una década.

Palabras Clave: Ovario. Carcinoma seroso de alto grado. Carcinoma endometrioide. Carcinoma de células claras. Carcinoma mucinoso. Carcinoma seroso de bajo grado.

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American Cancer Society. Cancer Facts & Figures 2024.

Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin 2024;74(1):12-49.
DOI: 10.3322/caac.21820

Barakat R, Berchuck A, Markman M, Randall ME. Principles and Practice of Gynecologic Oncology. 6th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2013.

Prat J. Pathology of the ovary. Philadelphia: Saunders; 2004. pp. 83-109.

Kurman RJ, Carcangiu ML, Herrington CS, Young RH, eds. WHO Classification of Tumours of Female Reproductive Organs. (4th edition). IARC: Lyon 2014. (Chapter 1: Tumours of the ovary). pp. 11-40.

Crum CP, Herfs M, Ning G, Bijron JG, Howitt BE, Jimenez CA, et al. Through the glass darkly: intraepithelial neoplasia, top-down differentiation, and the road to ovarian cancer. J Pathol 2013;231:402-12.
DOI: 10.1002/path.4263

Piek JM, van Diest PJ, Zweemer RP, Jansen JW, Poort-Keesom RJ, Menko FH, et al. Dysplastic changes in prophylactically removed fallopian tubes of women predisposed to developing ovarian cancer. J Pathol 2001;195:451-6.
DOI: 10.1002/path.1000

Lee Y, Miron A, Drapkin R, Nucci MR, Medeiros F, Saleemuddin A, et al. A candidate precursor to serous carcinoma that originates in the distal fallopian tube. J Pathol 2007;211:26-35.
DOI: 10.1002/path.2091

Kindelberger DW, Lee Y, Miron A, Hirsch MS, Feltmate C, Medeiros F, et al. Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: evidence for a causal relationship. Am J Surg Pathol 2007;31:161-9.
DOI: 10.1097/01.pas.0000213335.40358.47

Medeiros F, Muto MG, Lee Y, Elvin JA, Callahan MJ, Feltmate C, et al. The tubal fimbria is a preferred site for early adenocarcinoma in women with familial ovarian cancer syndrome. Am J Surg Pathol 2006;30:230-6.
DOI: 10.1097/01.pas.0000180854.28831.77

Powell CB, Kenley E, Chen LM, Crawford B, McLennan J, Zaloudek C, et al. Risk reducing salpingo-oophorectomy in BRCA mutation carriers: role of serial sectioning in the detection of occult malignancy. J Clin Oncol 2005;23:127-32.
DOI: 10.1200/JCO.2005.04.109

Folkins AK, Jarboe EA, Saleemuddin A, Lee Y, Callahan MJ, Drapkin R, et al. A candidate precursor to pelvic serous cancer (p53 signature) and its prevalence in ovaries and fallopian tubes from women with BRCA mutations. Gynecol Oncol 2008;109:168-73.
DOI: 10.1016/j.ygyno.2008.01.012

Obata K, Morland SJ, Watson RH, Hitchcock A, Chenevix-Trench G, Thomas EJ, et al. Frequent PTEN/MMAC mutations in endometrioid but not serous or mucinous epithelial ovarian tumors. Cancer Res 1998;58:2095-7.

Sato N, Tsunoda H, Nishida M, Morishita Y, Takimoto Y, Kubo T, et al. Loss of heterozygosity on 10q23.3 and mutation of the tumor suppressor gene PTEN in benign endometrial cyst of the ovary: possible sequence progression from benign endometrial cyst to endometrioid carcinoma and clear cell carcinoma of the ovary. Cancer Res 2000;60:7052-6.

Gilks CB, Prat J. Ovarian carcinoma pathology and genetics: recent advances. Hum Pathol 2009;40:1213-23.
DOI: 10.1016/j.humpath.2009.04.017

Prat J. Ovarian carcinomas: five distinct diseases with different origins, genetic alterations, and clinicopathological features. Virchows Arch 2012;460:237-49.
DOI: 10.1007/s00428-012-1203-5

Prat J, D'Angelo E, Espinosa I. Ovarian carcinomas: at least five different diseases with distinct histological features and molecular genetics. Hum Pathol 2018;80:11-27.
DOI: 10.1016/j.humpath.2018.06.018

Prat J. FIGO Committee on Gynecologic Oncology. Staging classification for cancer of the ovary, fallopian tube, and peritoneum. Int J Gynaecol Obstet 2014;124:1-5.
DOI: 10.1016/j.ijgo.2013.10.001

Soslow RA, Han G, Park KJ, Garg K, Olvera N, Spriggs DR, et al. Morphologic patterns associated with BRCA1 and BRCA2 genotype in ovarian carcinoma. Mod Pathol 2012;25:625-36.
DOI: 10.1038/modpathol.2011.183

Köbel M, Kalloger SE, Lee S, Duggan MA, Kelemen LE, Prentice L, et al; Ovarian Tumor Tissue Analysis Consortium. Biomarker-based ovarian carcinoma typing: a histologic investigation in the ovarian tumor tissue analysis consortium. Cancer Epidemiol Biomarkers Prev 2013;22:1677-86.
DOI: 10.1158/1055-9965.EPI-13-0391

Cuatrecasas M, Catasus L, Palacios J, Prat J. Transitional cell tumors of the ovary: a comparative clinicopathologic, immunohistochemical, and molecular genetic analysis of Brenner tumors and transitional cell carcinomas. Am J Surg Pathol 2009;33:556-67.
DOI: 10.1097/PAS.0b013e318188b84c

Ali RH, Seidman JD, Luk M, Kalloger S, Gilks CB. Transitional cell carcinoma of the ovary is related to high-grade serous carcinoma and is distinct from malignant Brenner tumor. Int J Gynecol Pathol 2012;31:499-506.
DOI: 10.1097/PGP.0b013e31824d7445

Heintz AP, Odicino F, Maisonneuve P, Quinn MA, Benedet JL, Creasman WT, et al. Carcinoma of the ovary. FIGO 26th Annual Report on the Results of Treatment in Gynecological Cancer. Int J Gynaecol Obstet 2006;95 Suppl 1:S161-192.
DOI: 10.1016/S0020-7292(06)60033-7

Onda T, Yoshikawa H, Yasugi T, Mishima M, Nakagawa S, Yamada M, et al. Patients with ovarian carcinoma upstaged to stage III after systematic lymphadenctomy have similar survival to Stage I/II patients and superior survival to other Stage III patients. Cancer 1998;83:1555-60.
DOI: 10.1002/(SICI)1097-0142(19981015)83:8<1555::AID-CNCR10>3.0.CO;2-R

Baek SJ, Park JY, Kim DY, Kim JH, Kim YM, Kim YT, et al. Stage IIIC epithelial ovarian cancer classified solely by lymph node metastasis has a more favorable prognosis than other types of stage IIIC epithelial ovarian cancer. J Gynecol Oncol 2008;19:223-8.
DOI: 10.3802/jgo.2008.19.4.223

Cancer Genome Atlas Research Network: Integrated genomic analysis of ovarian carcinoma. Nature 2011,474 609-15.
DOI: 10.1038/nature10166

Risch HA, McLaughlin JR, Cole DE, Rosen B, Bradley L, Fan I, et al. Population BRCA1 and BRCA2 mutation frequencies and cancer penetrances: a kin-cohort study in Ontario, Canada. J Natl Cancer Inst 2006;98:1694-706.
DOI: 10.1093/jnci/djj465

Geisler JP, Hatterman-Zogg MA, Rathe JA, Buller RE. Frequency of BRCA1 dysfunction in ovarian cancer. J Natl Cancer Inst 2002;94:61-67.
DOI: 10.1093/jnci/94.1.61

Esteller M, Silva JM, Dominguez G, Dominguez G, Bonilla F, Matias-Guiu X, et al. Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors. J Natl Cancer Inst 2000;92:564-9.
DOI: 10.1093/jnci/92.7.564

Patch AM, Christie EL, Etemadmoghadam D, Garsed DW, George J, Fereday S, et al. Whole-genome characterization of chemoresistant ovarian cancer. Nature 2015;521:489-94.
DOI: 10.1038/nature14410

Bowtell DD. The genesis and evolution of high-grade serous ovarian cancer. Nat Rev Cancer 2010;10:803-8.
DOI: 10.1038/nrc2946

Chen EY, Mehra K, Mehrad M, Ning G, Miron A, Mutter GL, et al. Secretory cell outgrowth, PAX2 and serous carcinogenesis in the Fallopian tube. J Pathol 2010;222:110-6.
DOI: 10.1002/path.2739

Howitt BE, Hanamornroongruang S, Lin DI, Conner JE, Schulte S, Horowitz N, et al. Evidence for a dualistic model of high-grade serous carcinoma: BRCA mutation status, histology, and tubal intraepithelial carcinoma. Am J Surg Pathol 2015;39:287-93.
DOI: 10.1097/PAS.0000000000000369

Przybycin CG, Kurman RJ, Ronnett BM, Shih IeM, Vang R. Are all pelvic (nonuterine) serous carcinomas of tubal origin? Am J Surg Pathol 2010;34:1407-16.
DOI: 10.1097/PAS.0b013e3181ef7b16

Morrison JC, Blanco LZ Jr, Vang R, Ronnett BM. Incidental serous tubal intraepithelial carcinoma and early invasive serous carcinoma in the nonprophylactic setting: analysis of a case series. Am J Surg Pathol 2015;39:442-53.
DOI: 10.1097/PAS.0000000000000352

Gilks CB, Irving J, Kobel M, Lee C, Singh N, Wilkinson N, et al. Incidental nonuterine high-grade serous carcinomas arise in the fallopian tube in most cases: further evidence for the tubal origin of high-grade serous carcinomas. Am J Surg Pathol 2015;39:357-64.
DOI: 10.1097/PAS.0000000000000353

Hirst JE, Gard GB, McIllroy K, Nevell D, Field M. High rates of occult fallopian tube cancer diagnosed at prophylactic bilateral salpingo-oophorectomy. Int J Gynecol Cancer 2009;19:826-9.
DOI: 10.1111/IGC.0b013e3181a1b5dc

Rabban JT, Garg K, Crawford B, Chen LM, Zaloudek CJ. Early detection of high-grade tubal serous carcinoma in women at low risk for hereditary breast and ovarian cancer syndrome by systematic examination of fallopian tubes incidentally removed during benign surgery. Am J Surg Pathol 2014;38:729-42.
DOI: 10.1097/PAS.0000000000000199

Tang S, Onuma K, Deb P, Wang E, Lytwyn A, Sur M, et al. Frequency of serous tubal intraepithelial carcinoma in various gynecologic malignancies: a study of 300 consecutive cases. Int J Gynecol Pathol 2012;31:103-0.
DOI: 10.1097/PGP.0b013e31822ea955

Falconer H, Yin L, Grönberg H, Altman D. Ovarian cancer risk after salpingectomy: a nationwide population-based study. J Natl Cancer Inst 2015;107(2):dju410.
DOI: 10.1093/jnci/dju410

McAlpine JN, Hanley GE, Woo MM, Tone AA, Rozenberg N, Swenerton KD, et al. Ovarian Cancer Research Program of British Columbia: Opportunistic salpingectomy: uptake, risks, and complications of a regional initiative for ovarian cancer prevention. Am J Obstet Gynecol 2014;210:471.e1-471.e11.
DOI: 10.1016/j.ajog.2014.01.003

Kuhn E, Meeker A, Wang TL, Sehdev AS, Kurman RJ, Shih IeM. Shortened telomeres in serous tubal intraepithelial carcinoma: an early event in ovarian high-grade serous carcinogenesis. Am J Surg Pathol 2010;34:829-36.
DOI: 10.1097/PAS.0b013e3181dcede7

Perets R, Wyant GA, Muto KW, Bijron JG, Poole BB, Chin KT, et al. Transformation of the fallopian tube secretory epithelium leads to high-grade serous ovarian cancer in Brca;Tp53;Pten models. Cancer Cell 2013;24:751-65.
DOI: 10.1016/j.ccr.2013.10.013

D'Angelo E, Espinosa I, Felicioni L, Buttitta F, Prat J. Ovarian high-grade serous carcinoma with transitional-like (SET) morphology: a homologous recombination-deficient tumor. Hum Pathol 2023;141:15-21.
DOI: 10.1016/j.humpath.2023.08.010

Byun JM, Cho HJ, Lee DS, Yoon HK, Kim YN, Im DH, et al. Frequency of serous tubal intraepithelial carcinoma (STIC) in patients with high grade serous ovarian cancer. Taiwan J Obstet Gynecol 2023;62(1):107-11.
DOI: 10.1016/j.tjog.2022.09.006

Yoon JY, Chapel DB, Goebel E, Qian X, Mito JK, Horowitz NS, et al. Genomic catastrophe, the peritoneal cavity and ovarian cancer prevention. J Pathol 2022;257(3):255-61.
DOI: 10.1002/path.5891

Kim J, Coffey DM, Ma L, Matzuk MM. The ovary is an alternative site of origin for high-grade serous ovarian cancer in mice. Endocrinology 2015;156:1975-81.
DOI: 10.1210/en.2014-1977

Löhmussaar K, Kopper O, Korving J, Begthel H, Vreuls CPH, van Es JH, et al. Assessing the origin of high-grade serous ovarian cancer using CRISPR-modification of mouse organoids. Nat Commun 2020;11:2660.
DOI: 10.1038/s41467-020-16432-0

Zhang S, Dolgalev I, Zhang T, Ran H, Levine DA, Neel BG. Both fallopian tube and ovarian surface epithelium are cells-of origin for high-grade serous ovarian carcinoma. Nat Commun 2019;10:5367.
DOI: 10.1038/s41467-019-13116-2

Moore K, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med 2018;379:2495-505.
DOI: 10.1056/NEJMoa1810858

Rowe BP, Glazer PM. Emergence of rationally designed therapeutic strategies for breast cancer targeting DNA repair mechanisms. Breast Cancer Res 2010;12(2):203.
DOI: 10.1186/bcr2566

González-Martín A, Pothuri B, Vergote I, DePont Christensen R, Graybill W, Mirza MR, et al. Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med 2019;381(25):2391-402.
DOI: 10.1056/NEJMoa1910962

Coleman RL, Fleming GF, Brady MF, Swisher EM, Steffensen KD, Friedlander M, et al. Veliparib with First-Line Chemotherapy and as Maintenance Therapy in Ovarian Cancer. N Engl J Med 2019;381(25):2403-15.
DOI: 10.1056/NEJMoa1909707

Westin SN, Michael V, Fellman BM, Meyer L, Taylor T, Alvarado T, et al. Neoadjuvant window trial in newly diagnosed BRCA mutant ovarian cancer. Gynecol Oncol 2023; 176:S2-S3.
DOI: 10.1016/j.ygyno.2023.06.467

Swisher E, Lin K, Oza A, Scott CL, Giordano H, Sun J, et al. Rucaparib in relapsed, platinum-sensitive high grade ovarian carcinoma (Ariel2 Part 1): an international multicenter, open-label, phase 2 trial. Lanc Onc 2017;18:75-87.
DOI: 10.1016/S1470-2045(16)30559-9

Mirza M, Monk B, Herrstedt J, Oza AM, Mahner S, Redondo A, et al. Niraparib Maintenance Therapy in Platinum-sensitive Recurrent Ovarian Cancer. N Engl J Med 2016;375:2154-64.
DOI: 10.1056/NEJMoa1611310

Gershenson DM, Sun CC, Lu KH, Coleman RL, Sood AK, Malpica A, et al. Clinical behavior of stage II-IV low-grade serous carcinoma of the ovary. Obstet Gynecol 2006;108:361-8.
DOI: 10.1097/01.AOG.0000227787.24587.d1

Prat J, De Nictolis M. Serous borderline tumors of the ovary: a long-term follow-up study of 137 cases, including 18 with a micropapillary pattern and 20 with microinvasion. Am J Surg Pathol 2002;26:1111-28.
DOI: 10.1097/00000478-200209000-00002

Kennedy AW, Hart WR. Ovarian papillary serous tumors of low malignant potential (serous borderline tumors). A long-term follow-up study, including patients with microinvasion, lymph node metastasis, and transformation to invasive serous carcinoma. Cancer 1996;78:278-86.
DOI: 10.1002/(SICI)1097-0142(19960715)78:2<278::AID-CNCR14>3.0.CO;2-T

Longacre TA, McKenney JK, Tazelaar HD, Kempson RL, Hendrickson MR. Ovarian serous tumors of low malignant potential (borderline tumors): outcome-based study of 276 patients with long-term (> or =5-year) follow-up. Am J Surg Pathol 2005;29:707-23.
DOI: 10.1097/01.pas.0000164030.82810.db

Singer G, Oldt R 3rd, Cohen Y, et al. Mutations in BRAF and KRAS characterize the development of low-grade ovarian serous carcinoma. J Natl Cancer Inst 2003;95:484-6.
DOI: 10.1093/jnci/95.6.484

Tsang YT, Deavers MT, Sun CC, Kwan SY, Kuo E, Malpica A, et al. KRAS (but not BRAF) mutations in ovarian serous borderline tumour are associated with recurrent low-grade serous carcinoma. J Pathol 2013;231:449-56.
DOI: 10.1002/path.4252

Jones S, Wang TL, Kurman RJ, Nakayama K, Velculescu VE, Vogelstein B, et al. Low-grade serous carcinomas of the ovary contain very few point mutations. J Pathol 2012;226:413-20.
DOI: 10.1002/path.3967

Emmanuel C, Chiew YE, George J, Etemadmoghadam D, Anglesio MS, Sharma R; Australian Ovarian Cancer Study (AOCS): Genomic classification of serous ovarian cancer with adjacent borderline differentiates RAS pathway and TP53-mutant tumors and identifies NRAS as an oncogenic driver. Clin Cancer Res 2014;20:6618-30.
DOI: 10.1158/1078-0432.CCR-14-1292

Sieben NL, Roemen GM, Oosting J, Fleuren GJ, van Engeland M, Prat J. Clonal analysis favours a monoclonal origin for serous borderline tumours with peritoneal implants. J Pathol 2006; 210:405-11.
DOI: 10.1002/path.2074

Tang M, O'Connell RL, Amant F, Beale P, McNally O, Sjoquist KM, Grant P, et al. PARAGON: A Phase II study of anastrozole in patients with estrogen receptor-positive recurrent/metastatic low-grade ovarian cancers and serous borderline ovarian tumors. Gynecol Oncol 2019;154(3):1-538.
DOI: 10.1016/j.ygyno.2019.06.011

Gershenson DM, Miller A, Brady WE, Paul J, Carty K, Rodgers W, Millan D, et al. Trametinib versus standard of care in patients with recurrent low-grade serous ovarian cancer (GOG 281/LOGS): an international, randomised, open-label, multicentre, phase 2/3 trial. Lancet 2022;399(10324):541-53.
DOI: 10.1016/S0140-6736(21)02175-9

Rodríguez IM, Prat J. Mucinous tumors of the ovary: a clinicopathologic analysis of 75 borderline tumors (of intestinal type) and carcinomas. Am J Surg Pathol 2002;26:139-52.
DOI: 10.1097/00000478-200202000-00001

Lee KR, Scully RE. Mucinous tumors of the ovary: a clinicopathologic study of 196 borderline tumors (of intestinal type) and carcinomas, including an evaluation of 11 cases with 'pseudomyxoma peritonei'. Am J Surg Pathol 2000;24:1447-64.
DOI: 10.1097/00000478-200011000-00001

Silverberg SG, Bell DA, Kurman RJ, Seidman D, Prat J, Ronnett BM, et al. Borderline ovarian tumors: key points and workshop summary. Hum Pathol 2004;35:910-7.
DOI: 10.1016/j.humpath.2004.03.003

Uzan C, Nikpayam M, Ribassin-Majed L, Goudy S, Bendifallah S, Cortez A, et al. Influence of histological subtypes on the risk of an invasive recurrence in a large series of stage I borderline ovarian tumor including 191 conservative treatments. Ann Oncol 2014;25:1312-9.
DOI: 10.1093/annonc/mdu139

Provenza C, Young RH, Prat J. Anaplastic carcinoma in mucinous ovarian tumors: a clinicopathologic study of 34 cases emphasizing the crucial impact of stage on prognosis, their histologic spectrum, and overlap with sarcomalike mural nodules. Am J Surg Pathol 2008;32:383-9.
DOI: 10.1097/PAS.0b013e3181451b93

Anglesio MS, Kommoss S, Tolcher MC, Clarke B, Galletta L, Porter H, Damaraju S, et al. Molecular characterization of mucinous ovarian tumours supports a stratified treatment approach with HER2 targeting in 19% of carcinomas. J Pathol 2013;229:111-20.
DOI: 10.1002/path.4088

Cheasley D, Wakefield MJ, Ryland GL, Allan PE, Alsop K, Amarasinghe KC, et al. The molecular origin and taxonomy of mucinous ovarian carcinoma. Nat Commun 2019;10:3935.
DOI: 10.1038/s41467-019-11862-x

Mackenzie R, Kommoss S, Winterhoff BJ, et al. BMC Cancer 2015;15:415.
DOI: 10.1186/s12885-015-1421-8

Nugawela D, Gorringe KL. Targeted therapy for mucinous ovarian carcinoma: evidence from clinical trials. Int J Gynecol Cancer 2023;33(1):102-8.
DOI: 10.1136/ijgc-2022-003658

Gorringe KL, Cheasley D, Wakefield MJ, Ryland GL, Allan PE, Alsop K, Amarasinghe KC, et al. Therapeutic options for mucinous ovarian carcinoma. Gynecol Oncol 2020;156(3):552-60.
DOI: 10.1016/j.ygyno.2019.12.015

Irving JA, Catasús L, Gallardo A, Bussaglia E, Romero M, Matias-Guiu X, et al. Synchronous endometrioid carcinomas of the uterine corpus and ovary: alterations in the beta-catenin (CTNNB1) pathway are associated with independent primary tumors and favorable prognosis. Hum Pathol 2005;36:605-19.
DOI: 10.1016/j.humpath.2005.03.005

Wiegand KC, Shah SP, Al-Agha OM, Zhao Y, Tse K, Zeng T, et al. ARID1A mutations in endometriosis-associated ovarian carcinomas. N Engl J Med 2010;363:1532-43.
DOI: 10.1056/NEJMoa1008433

Palacios J, Gamallo C. Mutations in the beta-catenin gene (CTNNB1) in endometrioid ovarian carcinomas. Cancer Res 1998;58:1344-7.

Catasús L, Bussaglia E, Rodriguez I, Gallardo A, Pons C, Irving JA, et al. Molecular genetic alterations in endometrioid carcinomas of the ovary: similar frequency of beta-catenin abnormalities but lower rate of microsatellite instability and PTEN alterations than in uterine endometrioid carcinomas. Hum Pathol 2004; 35:1360-8.
DOI: 10.1016/j.humpath.2004.07.019

Gras E, Catasus L, Argüelles R, Moreno-Bueno G, Palacios J, Gamallo C, et al. Microsatellite instability, MLH-1 promoter hypermethylation, and frameshift mutations at coding mononucleotide repeat microsatellites in ovarian tumors. Cancer 2001;92:2829-36.
DOI: 10.1002/1097-0142(20011201)92:11<2829::AID-CNCR10094>3.0.CO;2-3

Campbell IG, Russell SE, Choong DY, Montgomery KG, Ciavarella ML, Hooi CS, et al. Mutation of the PIK3CA gene in ovarian and breast cancer. Cancer Res 2004; 64:7678-81.
DOI: 10.1158/0008-5472.CAN-04-2933

Catasus L, Gallardo A, Cuatrecasas M, Prat J. PIK3CA mutations in the kinase domain (exon 20) of uterine endometrial adenocarcinomas are associated with adverse prognostic parameters. Mod Pathol 2008;21:131-9.
DOI: 10.1038/modpathol.3800992

Banerjee S and Kaye S. New strategies in the treatment of ovarian cancer: current clinical perspectives and future potential. Amr Assc for Cancer Res 2013;19:961-8.
DOI: 10.1158/1078-0432.CCR-12-2243

Liu P, Cheng H, Roberts TM. Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov 2009; 8:627-44.
DOI: 10.1038/nrd2926

Leskela S, Romero I, Rosa-Rosa JM, Caniego-Casas T, Cristobal E, Pérez-Mies B, et al. Molecular Heterogeneity of Endometrioid Ovarian Carcinoma: An Analysis of 166 Cases Using the Endometrial Cancer Subrogate Molecular Classification. Am J Surg Pathol 2020;44:982-90.
DOI: 10.1097/PAS.0000000000001478

Parra-Herran C, Lerner-Ellis J, Xu B, Khalouei S, Bassiouny D, Cesari M, et al. Molecular-based classification algorithm for endometrial carcinoma categorizes ovarian endometrioid carcinoma into prognostically significant groups. Mod Pathol 2017;30:1748-59.
DOI: 10.1038/modpathol.2017.81

Cybulska P, Paula ADC, Tseng J, Leitao MM Jr, Bashashati A, Huntsman DG, et al. Molecular profiling and molecular classification of endometrioid ovarian carcinomas. Gynecol Oncol 2019;154:516-23.
DOI: 10.1016/j.ygyno.2019.07.012

Schultheis AM, Ng CK, De Filippo MR, Piscuoglio S, Macedo GS, Gatius S, et al. Massively Parallel Sequencing-Based Clonality Analysis of Synchronous Endometrioid Endometrial and Ovarian Carcinomas. J Natl Cancer Inst 2016;108(6):djv427.
DOI: 10.1093/jnci/djv427

Anglesio MS, Wang YK, Maassen M, Horlings HM, Bashashati A, Senz J, et al. Synchronous endometrial and ovarian carcinomas: evidence of clonality. J Natl Cancer Inst 2016;108(6):djv428.
DOI: 10.1093/jnci/djv428

Komiyama S, Aoki D, Tominaga E, Susumu N, Udagawa Y, Nozawa S. Prognosis of Japanese patients with ovarian clear cell carcinoma associated with pelvic endometriosis: clinicopathologic evaluation. Gynecol Oncol 1999;72:342-6.
DOI: 10.1006/gyno.1998.5284

Kuo KT, Mao TL, Jones S, Veras E, Ayhan A, Wang TL, et al. Frequent activating mutations of PIK3CA in ovarian clear cell carcinoma. Am J Pathol 2009;174:1597-601.
DOI: 10.2353/ajpath.2009.081000

Yamamoto S, Tsuda H, Takano M, Iwaya K, Tamai S, Matsubara O. PIK3CA mutation is an early event in the development of endometriosis-associated ovarian clear cell adenocarcinoma. J Pathol 2011;225:189-94.
DOI: 10.1002/path.2940

Willner J, Wurz K, Allison KH, Galic V, Garcia RL, Goff BA, et al. Alternate molecular genetic pathways in ovarian carcinomas of common histological types. Hum Pathol 2007;38:607-13.
DOI: 10.1016/j.humpath.2006.10.007

Folkins AK, Longacre TA. Hereditary gynaecological malignancies: advances in screening and treatment. Histopathology 2013;62:2-30.
DOI: 10.1111/his.12028

Chui MH, Ryan P, Radigan J, Ferguson SE, Pollett A, Aronson M, et al. The histomorphology of Lynch syndrome associated ovarian carcinomas: towards a subtype-specific screening strategy. Am J Surg Pathol 2014;38:1173-81.
DOI: 10.1097/PAS.0000000000000298

Stewart CJR, Bowtell DDL, Doherty DA, Leung YC, Long-term survival of patients with mismatch repair protein-deficient, high-stage ovarian clear cell carcinoma. Histopathology 2017;70:309-13.
DOI: 10.1111/his.13040

Howitt BE, Strickland KC, Sholl LM, Rodig S, Ritterhouse LL, Chowdhury D, et al. Clear cell ovarian cancers with microsatellite instability: a unique subset of ovarian cancers with increased tumor-infiltrating lymphocytes and PD-1/PD-L1 expression. Oncoimmunology 2017;6:e1277308.
DOI: 10.1080/2162402X.2016.1277308

100. Irshaid L, Costigan DC, Dong F, Matulonis UA, Nucci MR, Kolin DL. Molecular Landscape of Mullerian Clear Cell Carcinomas Identifies The Cancer Genome Atlas-like Prognostic Subgroups. Mod Pathol 2023;36(5):100123.
DOI: 10.1016/j.modpat.2023.100123