Clinicopathological and genetic characterization of radiotherapy-induced undifferentiated pleomorphic sarcoma following breast cancer: a case series of three tumors and comprehensive literature review.
COL3A1-GULP1
RB1
TP53
Poor prognosis
Radiotherapy-induced sarcoma (RIS)
Undifferentiated pleomorphic sarcoma (UPS)
Journal
Diagnostic pathology
ISSN: 1746-1596
Titre abrégé: Diagn Pathol
Pays: England
ID NLM: 101251558
Informations de publication
Date de publication:
15 Aug 2024
15 Aug 2024
Historique:
received:
02
04
2024
accepted:
30
07
2024
medline:
15
8
2024
pubmed:
15
8
2024
entrez:
14
8
2024
Statut:
epublish
Résumé
Compared to primary breast sarcoma (BSs), radiotherapy-induced sarcoma (RIS) is a less frequent type of secondary breast sarcoma. Undifferentiated pleomorphic sarcoma (UPS) is an even rarer occurrence within the RIS category. This study aimed to present the clinicopathologic and molecular features of breast radiotherapy-induced UPS. A retrospective study was conducted at the Third Affiliated Hospital of Soochow University to analyze three patients with radiation-induced undifferentiated pleomorphic sarcoma (UPS) following breast cancer, spanning from 2006 to 2023. The clinical and pathological variables were extracted from the medical records, while immunohistochemistry was employed to analyze the immunophenotypes of these tumors. Genomic characteristics were assessed through DNA and RNA sequencing techniques. Another 15 cases from the literature were also reviewed to better characterize the tumor. The affected areas encompass the chest wall and breasts, with an incubation period ranging from 6 to 17 years. The tumor cells exhibit pleomorphism and demonstrate a high degree of pathological mitosis. Notably, two cases displayed an accelerated disease progression, characterized by recurrent tumors and metastases occurring within short intervals of 48 and 7 months respectively subsequent to the initial diagnosis. The two prevailing identified genes were TP53 (2/3, 66.7%) and RB1 (1/3, 33.3%). Through analysis of somatic copy number variation (CNV), it was discovered that two oncogenes, MCL1 (1/3, 33.3%) and MYC (1/3, 33.3%), had experienced gains in CNV. The Tumor Mutational Burden (TMB) values for case 1, case 2, and case 3 were 5.9 mut/Mb, 1.0 mut/Mb, and 3.0 mut/Mb, respectively. Moreover, the analysis of RNA-NGS (next-generation sequencing) revealed the presence of a novel gene fusion, named COL3A1-GULP1, in case 2. Based on our thorough analysis of research findings and previous reports, it is evident that radiotherapy-induced UPS exhibits a highly diverse and frequently severe clinical and biological behavior. Identifying tumor formation using genome sequencing can help understand its biological behavior and determine personalized treatments.
Identifiants
pubmed: 39143618
doi: 10.1186/s13000-024-01534-w
pii: 10.1186/s13000-024-01534-w
doi:
Substances chimiques
Biomarkers, Tumor
0
RB1 protein, human
0
Retinoblastoma Binding Proteins
0
Ubiquitin-Protein Ligases
EC 2.3.2.27
Types de publication
Journal Article
Case Reports
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
110Subventions
Organisme : Ting Lei
ID : QN202114
Organisme : Qing Li
ID : 2022260
Informations de copyright
© 2024. The Author(s).
Références
Rakha EAR-FJ, Sasano H, Wu Y. WHO classifcation of tumours editorial board: breast tumours. WHO classifcation of tumours series, 5th ed.; 2019.
Lim SZ, Ong KW, Tan BK, Selvarajan S, Tan PH. Sarcoma of the breast: an update on a rare entity. J Clin Pathol. 2016;69(5):373–81.
doi: 10.1136/jclinpath-2015-203545
pubmed: 26729013
Sheth GR, Cranmer LD, Smith BD, Grasso-Lebeau L, Lang JE. Radiation-induced sarcoma of the breast: a systematic review. Oncologist. 2012;17(3):405–18.
doi: 10.1038/s41379-019-0300-2
pubmed: 31243333
Kong J, Shahait AD, Kim S, Choi L. Radiation-induced undifferentiated pleomorphic sarcoma of the breast. BMJ Case Rep. 2020;13(2):e232616
Srinivasamurthy BC, Kulandaivelu AR, Saha K, Saha A. Primary undifferentiated pleomorphic sarcoma of the breast in a young female: a case report. World J Surg Oncol. 2016;14(1):186.
doi: 10.1186/s12957-016-0947-9
pubmed: 27421259
pmcid: 4947292
Yamazaki H, Shimizu S, Yoshida T, Suganuma N, Yamanaka T, Yamashita T, Rino Y, Masuda M. A case of undifferentiated pleomorphic sarcoma of the breast with lung and bone metastases. Int J Surg Case Rep. 2018;51:143–6.
doi: 10.1016/j.ijscr.2018.07.049
pubmed: 30165321
pmcid: 6117951
Gambichler T, Horny K, Mentzel T, Stricker I, Tannapfel A, Scheel CH, Behle B, Quast DR, Lee YP, Stucker M, et al. Undifferentiated pleomorphic sarcoma of the breast with neoplastic fever: case report and genomic characterization. J Cancer Res Clin Oncol. 2023;149(4):1465–71.
doi: 10.1007/s00432-022-04000-6
pubmed: 35501497
Hartel PH, Bratthauer G, Hartel JV, Fanburg-Smith JC. Primary malignant fibrous histiocytoma (myxofibrosarcoma/pleomorphic sarcoma not otherwise specified) of the breast: clinicopathologic study of 19 cases. Ann Diagn Pathol. 2011;15(6):407–13.
doi: 10.1016/j.anndiagpath.2011.05.007
Vera-Sempere F, Llombart-Bosch A. Malignant fibrohistiocytoma (MFH) of the breast. Primary and postirradiation variants - an ultrastructural study. Pathol Res Pract. 1984;178(3):289–96.
doi: 10.1016/S0344-0338(84)80112-0
pubmed: 6326070
Gladdy RA, Qin LX, Moraco N, Edgar MA, Antonescu CR, Alektiar KM, Brennan MF, Singer S. Do radiation-associated soft tissue sarcomas have the same prognosis as sporadic soft tissue sarcomas? J Clin Oncol. 2010;28(12):2064–9.
doi: 10.1200/JCO.2009.25.1728
pubmed: 20308666
pmcid: 3651600
Riad S, Biau D, Holt GE, Werier J, Turcotte RE, Ferguson PC, Griffin AM, Dickie CI, Chung PW, Catton CN, O’sullivan B, Wunder JS. The clinical and functional outcome for patients with radiation-induced soft tissue sarcoma. Cancer. 2012;118(10):2682–92.
doi: 10.1002/cncr.26543
pubmed: 21989796
Kokkali S, Moreno JD, Klijanienko J, Theocharis S. Clinical and molecular insights of Radiation-Induced breast sarcomas: Is there hope on the Horizon for Effective Treatment of this aggressive disease? Int J Mol Sci. 2022;23(8):4125.
Lei T, Yang Y, Shi Y, Deng X, Peng Y, Wang H, Chen T. Clinicopathological features and genomic profiles of a group of secretory breast carcinomas in which progressive cases have more complex genomic features. Diagn Pathol. 2022;17(1):101.
Mery CM, George S, Bertagnolli MM, Raut CP. Secondary sarcomas after radiotherapy for breast cancer: sustained risk and poor survival. Cancer. 2009;115(18):4055–63.
doi: 10.1634/theoncologist.2011-0282
pubmed: 22334455
pmcid: 3316927
Hardy TJ, An T, Brown PW, Terz JJ. Postirradiation sarcoma (malignant fibrous histiocytoma) of axilla. Cancer. 1978;42(1):118–24.
doi: 10.1002/cncr.24462
pubmed: 19526590
Tsuneyoshi M, Enjoji M. Postirradiation sarcoma (malignant fibrous histiocytoma) following breast carcinoma: an ultrastructural study of a case. Cancer. 1979;45(6):1419–23.
doi: 10.1002/gcc.20827
pubmed: 20949568
pmcid: 3150534
Meunier B, Levêque J, Prisé EL,Kerbrat P, Grall JY. Three cases of sarcoma occurring after radiation therapy of breast cancers. Eur J Obstet Gynecol Reprod Biol. 1994;57(1):33–6.
doi: 10.1016/j.pharmthera.2019.06.010
pubmed: 31276706
pmcid: 6746598
Kirova YM, Vilcoq JR, Asselain B, Sastre-Garau X, Fourquet A. Radiation-induced sarcomas after radiotherapy for breast carcinoma: a large-scale single-institution review. Cancer. 2005;104(4):856–63.
doi: 10.1016/j.humpath.2022.02.006
pubmed: 35181378
Horii R, Fukuuchi A, Nishi T, Takanashi R. A case of malignant fibrous histiocytoma after breast conserving therapy for breast cancer. Breast Cancer. 2000;7(1):75–7.
doi: 10.1016/j.cell.2017.10.014
Komaei I, Guccione F, Sarra F, Palmeri E, Ieni A, Cardia R, Currò G, Navarra G, Palmeri R. Radiation-induced undifferentiated pleomorphic sarcoma of the breast: a rare but serious complication following breast-conserving therapy. A case report and literature review. G Chir. 2019;40(6):544–50.
doi: 10.1002/path.5176
pubmed: 30281149
Hatta N, Horita Y. Undifferentiated pleomorphic sarcoma in a patient with Cowden syndrome after radiotherapy for breast cancer. J Dermatol. 2019;46(2):e73–5.
doi: 10.1016/j.trecan.2019.03.005
pubmed: 31174843
pmcid: 6719339
Kadouri L, Sagi M, Goldberg Y, Lerer I, Hamburger T, Peretz T. Genetic predisposition to radiation induced sarcoma: possible role for BRCA and p53 mutations. Breast Cancer Res Treat. 2013;140(1):207–11.
doi: 10.1038/s42003-021-02564-6
pubmed: 34475520
pmcid: 8413315
Noh JM, Huh SJ, Choi DH, Park W, Nam SJ. Two cases of post-radiation sarcoma after breast cancer treatment. J Breast Cancer. 2012;15(3):364–70.
Quadros CA, Vasconcelos A, Andrade R, Ramos RS, Studart E, Nascimento G, Trajano A. Good outcome after neoadjuvant chemotherapy and extended surgical resection for a large radiation-induced high-grade breast sarcoma. Int Semin Surg Oncol. 2006;3:18.
doi: 10.1158/1541-7786.MCR-18-0963
pubmed: 30777879
pmcid: 6548646
S M Pierce, A Recht, T I Lingos, A Abner, F Vicini, B Silver, A Herzog, J R Harris. Long-term radiation complications following conservative surgery (CS) and radiation therapy (RT) in patients with early stage breast cancer.Int J Radiat Oncol Biol Phys. 1992;23(5):915–23
doi: 10.1038/jhg.2013.132
pubmed: 24369359
Joo MW, Kang YK, Ogura K, Iwata S, Kim JH, Jeong WJ, Niu XH, Chinder PS, Kim HS, Seo SW, Chung YG. Post-radiation sarcoma: A study by the Eastern Asian Musculoskeletal Oncology Group. PLOS ONE. 2018;13(10):e0204927.
doi: 10.1111/his.12622
pubmed: 25407018
Cui YY, Han LY, Shang JF, Fang W, Zhao M, Chen D, Liu HG. Primary cardiac undifferentiated pleomorphic sarcoma is associated with TP53 mutation during lack of MDM2 amplification, and targeted sequencing analysis reveals potentially actionable targets. Hum Pathol. 2022;123:113–22.
doi: 10.1172/JCI139080
pubmed: 33016928
pmcid: 7598061
Lesluyes T, Baud J, Perot G, Charon-Barra C, You A, Valo I, Bazille C, Mishellany F, Leroux A, Renard-Oldrini S,Terrier P, Cesne AL, Laé M, Piperno-Neumann S, Sylvie Bonvalot S, Neuville A, Collin F, Maingon P, Coindre JM, Chibon F. Genomic and transcriptomic comparison of post-radiation versus sporadic sarcomas. Mod Pathol. 2019;32(12):1786–94.
doi: 10.1111/his.14433
pubmed: 34165212
pmcid: 8678905
Cancer Genome Atlas Research Network. Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas. Cell. 2017;171(4):950–65.
doi: 10.1158/0008-5472.CAN-10-3590
pubmed: 21406400
pmcid: 3076947
Thoenen E, Curl A, Iwakuma T. TP53 in bone and soft tissue sarcomas. Pharmacol Ther. 2019;202:149–64.
doi: 10.1038/s41568-021-00367-9
pubmed: 34188192
Ali NM, Niada S, Brini AT, Morris MR, Kurusamy S, Alholle A, Huen D, Antonescu CR, Tirode F, Sumathi V, Latif F. Genomic and transcriptomic characterisation of undifferentiated pleomorphic sarcoma of bone. J Pathol. 2019;247(2):166–76.
doi: 10.1080/14728222.2020.1723548
pubmed: 32003251
Petry V, Bonadio RC, Cagnacci AQC, Senna LAL, Campos RdNG, Cotti GC, Hoff PM, Fragoso MCBV, Estevez-Diz MDP. Radiotherapy-induced malignancies in breast cancer patients with TP53 pathogenic germline variants (Li–Fraumeni syndrome). Familial Cancer. 2020;19(1):47–53.
doi: 10.1158/2159-8290.CD-15-0507
pubmed: 26382145
pmcid: 4592441
Knudsen ES, Pruitt SC, Hershberger PA, Witkiewicz AK, Goodrich DW. Cell Cycle and Beyond: Exploiting New RB1 Controlled Mechanisms for Cancer Therapy. Trends Cancer. 2019;5(5):308–24.
doi: 10.1128/MCB.23.16.5738-5754.2003
pubmed: 12897145
pmcid: 166341
Di Fiore R, D'Anneo A, Tesoriere G, Vento R. RB1 in cancer: different mechanisms of RB1 inactivation and alterations of pRb pathway in tumorigenesis. J Cell Physiol. 2013;228(8):1676–87.
doi: 10.1016/j.molonc.2013.02.015
pubmed: 23523308
pmcid: 5528411
Widden H, Placzek WJ. The multiple mechanisms of MCL1 in the regulation of cell fate. Commun Biol. 2021;4(1):1029.
Hong AL, Guerriero JL, Doshi MB, Kynnap BD, Kim WJ, Schinzel AC, Modiste R, Schlauch AJ, Adam RM, Kwiatkowski DJ, Beroukhim R, Letai A, Rosenberg JE, Hahn WC. MCL1 and DEDD Promote Urothelial Carcinoma Progression. Mol Cancer Res. 2019;17(6):1294–304.
Stine ZE, Walton ZE, Altman BJ, Hsieh AL, Dang CV. MYC, Metabolism, and Cancer. Cancer Discov. 2015;5(10):1024–39.
Sio TT, Mansfield AS, Grotz TE, Graham RP, Molina JR, Que FG, Miller RC. Concurrent MCL1 and JUN amplification in pseudomyxoma peritonei: a comprehensive genetic profiling and survival analysis. J Hum Genet. 2014;59(3):124–8.
Vrana JA, Bieszczad CK, Cleaveland ES, Ma Y, Park JP, Mohandas TK, Craig RW. An MCL1-overexpressing Burkitt lymphoma subline exhibits enhanced survival on exposure to serum deprivation, topoisomerase inhibitors, or staurosporine but remains sensitive to 1-beta-D-arabinofuranosylcytosine. Cancer Res. 2002;62(3):892–900.
Allen TD, Zhu CQ, Jones KD, Yanagawa N, Tsao MS, Bishop JM. Interaction between MYC and MCL1 in the genesis and outcome of non-small-cell lung cancer. Cancer Res. 2011;71(6):2212–21.
Lourenco C, Resetca D, Redel C, Lin P, MacDonald AS, Ciaccio R, Kenney TMG, Wei Y, Andrews DW, Sunnerhagen M, Arrowsmith CH, Raught B, Penn LZ. MYC protein interactors in gene transcription and cancer. Nat Rev Cancer. 2021;21(9):579–91.
Dang CV. MYC on the path to cancer. Cell. 2012;149(1):22–35.
Romieu-Mourez R, Kim DW, Shin SM, Demicco EG, Landesman-Bollag E, Seldin DC, Cardiff RD, Sonenshein GE. Mouse mammary tumor virus c-rel transgenic mice develop mammary tumors. Mol Cell Biol. 2003;23(16):5738–54.
Morton JP, Sansom OJ. MYC-y mice: from tumour initiation to therapeutic targeting of endogenous MYC. Mol Oncol. 2013;7(2):248–58.
Tron AE, Belmonte MA, Adam A, Aquila BM, Boise LH, Chiarparin E, Cidado J, Embrey KJ, Gangl E, Gibbons FD, Gregory GP, Hargreaves D, Hendricks JA, Johannes JW, Johnstone RW, Kazmirski SL, Kettle JG, Lamb ML, Matulis SM, Nooka AK, Packer MJ, Peng B, Rawlins PB, Robbins DW, Schuller AG, Su N, Yang W, Ye Q, Zheng X, Secrist JP, Clark EA, Wilson DM, Fawell SE, Hird AW. Discovery of Mcl-1-specific inhibitor AZD5991 and preclinical activity in multiple myeloma and acute myeloid leukemia. Nat Commun. 2018;9(1):5341.
Jovanović KK, Roche-Lestienne C, Ghobrial IM, Facon T, Quesnel B, Manier S. Targeting MYC in multiple myeloma. Leukemia. 2018;32(6):1295–306.
Fitzel R, Secker-Grob KA, Keppeler H, Korkmaz F, Schairer R, Erkner E, Schneidawind D, Lengerke C, Hentrich T, Schulze-Hentrich JM, Schneidawind C. Targeting MYC in combination with epigenetic regulators induces synergistic anti-leukemic effects in MLLr leukemia and simultaneously improves immunity. Neoplasia. 2023;41:100902.
Hofvander J, Puls F, Pillay N, Steele CD, Flanagan AM, Magnusson L, Nilsson J, Mertens F. Undiferentiated peomorphic sarcomas with PRDMl0 fusions have a distinct gene expresion profile. J Pathol. 2019;249(4):425–34.
Hofvander J, Tayebwa J, Nilsson J, Magnusson L, Brosjö O, Larsson O, Vult von Steyern F, Mandahl N, Fletcher CD, Mertens F. Recurrent PRDM10 gene fusions in undifferentiated pleomorphic sarcoma. Clin Cancer Res. 2015;21(4):864–9.