PD-L1 and Mismatch Repair Status in Uterine Carcinosarcomas.
Journal
International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists
ISSN: 1538-7151
Titre abrégé: Int J Gynecol Pathol
Pays: United States
ID NLM: 8214845
Informations de publication
Date de publication:
01 Nov 2021
01 Nov 2021
Historique:
pubmed:
17
12
2020
medline:
14
1
2022
entrez:
16
12
2020
Statut:
ppublish
Résumé
Uterine carcinosarcomas have few adjuvant treatment options. Programmed cell death ligand-1 (PD-L1) expression in these tumors may predict response to checkpoint inhibitor therapies. An increase in PD-L1 expression has been shown in endometrial carcinomas with mismatch repair (MMR) deficiencies; however, few studies have evaluated PD-L1 expression in uterine carcinosarcomas. We examined PD-L1 expression in 41 cases of uterine carcinosarcoma using combined positive scores (CPS) and tumor proportion scores (TPS), and correlated with MMR status, p53 expression, and epithelial histotype. In addition to confirming the diagnosis of carcinosarcoma, the epithelial components were stratified based on endometrioid versus serous histology. Thirty-three cases (80%) were positive for PD-L1, defined as a CPS score of ≥1 or a TPS score of ≥1%. Twelve cases (29%) showed high expression of PD-L1, defined as a CPS score of ≥10 or a TPS score of ≥10%. The majority of the morphologically adjudicated carcinosarcomas had a serous epithelial component (83%) rather than endometrioid (17%), which was reinforced by aberrant p53 staining predominantly within cases with serous morphology. The majority of carcinosarcomas showed at least focal PD-L1 expression, predominantly in tumor-associated immune cells. Carcinosarcomas with endometrioid morphology were significantly more likely to have high-level PD-L1 (5/7 vs. 7/34; P=0.015). MMR-deficient carcinosarcomas were also more likely to have high-level PD-L1 (2/3 vs. 10/28); however, this did not reach statistical significance (P=0.2) and overall MMR-deficiency was uncommon (3 cases, 7%). These findings suggest that PD-L1 may be additive to MMR testing as a predictive biomarker for checkpoint inhibitor vulnerability in carcinosarcomas.
Identifiants
pubmed: 33323859
pii: 00004347-202111000-00006
doi: 10.1097/PGP.0000000000000752
doi:
Substances chimiques
B7-H1 Antigen
0
CD274 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
563-574Informations de copyright
Copyright © 2020 by the International Society of Gynecological Pathologists.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
Références
Cantrell LA, Blank SV, Duska LR. Uterine carcinosarcoma: a review of the literature. Gynecol Oncol 2015;137:581–8.
Frenel JS, Le Tourneau C, O’Neil B, et al. Safety and efficacy of pembrolizumab in advanced, programmed death ligand 1-positive cervical cancer: results from the phase Ib KEYNOTE-028 Trial. J Clin Oncol 2017;35:4035–41.
Chung HC, Ros W, Delord JP, et al. Efficacy and safety of pembrolizumab in previously treated advanced cervical cancer: results from the phase II KEYNOTE-158 study. J Clin Oncol 2019;37:1470–8.
Ott PA, Bang YJ, Berton-Rigaud D, et al. Safety and antitumor activity of pembrolizumab in advanced programmed death ligand 1–positive endometrial cancer: results from the KEYNOTE-028 study. J Clin Oncol 2017;35:2535–41.
Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science (80-) 2017;357:409–13.
Sloan EA, Ring KL, Willis BC, et al. PD-L1 expression in mismatch repair-deficient endometrial carcinomas, including lynch syndrome-associated and MLH1 promoter hypermethylated tumors. Am J Surg Pathol 2017;41:326–33.
Howitt BE, Shukla SA, Sholl LM, et al. Association of polymerase e-mutated and microsatellite-instable endometrial cancers with neoantigen load, number of tumor-infiltrating lymphocytes, and expression of PD-1 and PD-L1. JAMA Oncol 2015;1:1319–23.
Mills AM, Longacre TA. Lynch syndrome screening in the gynecologic tract current state of the art. Am J Surg Pathol 2016;40:e35–44.
Mills AM, Liou S, Ford JM, et al. Lynch syndrome screening should be considered for all patients with newly diagnosed endometrial cancer. Am J Surg Pathol 2014;38:1501–9.
Broaddus RR, Lynch HT, Chen LM, et al. Pathologic features of endometrial carcinoma associated with HNPCC: a comparison with sporadic endometrial carcinoma. Cancer 2006;106:87–94.
Conlon N, Da Cruz Paula A, Ashley CW, et al. Endometrial carcinomas with a “serous” component in young women are enriched for DNA mismatch repair deficiency, Lynch syndrome, and POLE exonuclease domain mutations. Am J Surg Pathol 2020;44:641–8.
Jenkins TM, Hanley KZ, Schwartz LE, et al. Mismatch repair deficiency in uterine carcinosarcoma: a multi-institution retrospective review. Am J Surg Pathol 2020;44:782–92.
Hoang LN, Ali RH, Lau S, et al. Immunohistochemical survey of mismatch repair protein expression in uterine sarcomas and carcinosarcomas. Int J Gynecol Pathol 2014;33:483–91.
Taylor NP, Zighelboim I, Huettner PC, et al. DNA mismatch repair and TP53 defects are early events in uterine carcinosarcoma tumorigenesis. Mod Pathol 2006;19:1333–8.
Cherniack AD, Shen H, Walter V, et al. Integrated molecular characterization of uterine carcinosarcoma. Cancer Cell 2017;31:411–23.
Saijo M, Nakamura K, Ida N, et al. Histologic appearance and immunohistochemistry of DNA mismatch repair protein and p53 in endometrial carcinosarcoma. Am J Surg Pathol 2019;43:1493–1500.
Jones TE, Pradhan D, Dabbs DJ, et al. Immunohistochemical markers with potential diagnostic, prognostic, and therapeutic significance in uterine carcinosarcoma: a clinicopathologic study of 43 cases. Int J Gynecol Pathol 2019. [Epub ahead of print].
Pinto A, MacKrides N, Nadji M. PD-L1 expression in carcinosarcomas of the gynecologic tract: a potentially actionable biomarker. Appl Immunohistochem Mol Morphol 2018;26:393–7.
Hacking S, Chavarria H, Jin C, et al. Landscape of immune checkpoint inhibition in carcinosarcoma (MMMT): analysis of IDO-1, PD-L1 and PD-1. Pathol Res Pract 2020;216:152847.
Kurman RJ, Carcangiu ML, Herrington CS, et al. WHO Classification of Tumours of Female Reproductive Organs, 4th ed. Lyon, France: International Agency for Research on Cancer (IARC); 2014.
Xu H, Lin G, Huang C, et al. Assessment of concordance between 22C3 and SP142 immunohistochemistry assays regarding PD-L1 expression in non-small cell lung cancer. Sci Rep 2017;7:16956.
Rimm DL, Han G, Taube JM, et al. A prospective, multi-institutional, pathologist-based assessment of 4 immunohistochemistry assays for PD-L1 expression in non-small cell lung cancer. JAMA Oncol 2017;3:1051–8.
Kulangara K, Zhang N, Corigliano E, et al. Clinical utility of the combined positive score for programmed death ligand-1 expression and the approval of pembrolizumab for treatment of gastric cancer. Arch Pathol Lab Med 2019;143:330–7.
Getz G, Gabriel SB, Cibulskis K, et al. Integrated genomic characterization of endometrial carcinoma. Nature 2013;497:67–73.
Makker V, Rasco D, Vogelzang NJ, et al. Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer: an interim analysis of a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol 2019;20:711–8.
FDA. FDA takes first action under new international collaboration with Australia and Canada designed to provide a framework for concurrent review of cancer therapies, approving treatment for patients with endometrial carcinoma. Available at: https://www.fda.gov/news-events/press-announcements/fda-takes-first-action-under-new-international-collaboration-australia-and-canada-designed-provide . Accessed May 13, 2020.
Konstantinopoulos PA, Luo W, Liu JF, et al. Phase II study of avelumab in patients with mismatch repair deficient and mismatch repair proficient recurrent/persistent endometrial cancer. J Clin Oncol 2019;37:2786–94.
Mills A, Zadeh S, Sloan E, et al. Indoleamine 2,3-dioxygenase in endometrial cancer: a targetable mechanism of immune resistance in mismatch repair-deficient and intact endometrial carcinomas. Mod Pathol 2018;31:1282–90.
Mo Z, Liu J, Zhang Q, et al. Expression of PD-1, PD-L1 and PD-L2 is associated with differentiation status and histological type of endometrial cancer. Oncol Lett 2016;12:944–50.
Shukla SA, Howitt BE, Wu CJ, et al. Predicted neoantigen load in non-hypermutated endometrial cancers: correlation with outcome and tumor-specific genomic alterations. Gynecol Oncol Reports 2017;19:42–5.
Konstantinopoulos PA, Waggoner S, Vidal GA, et al. Single-arm phases 1 and 2 trial of niraparib in combination with pembrolizumab in patients with recurrent platinum-resistant ovarian carcinoma. JAMA Oncol 2019;5:1141–9.
Varga A, Piha-Paul S, Ott PA, et al. Pembrolizumab in patients with programmed death ligand 1–positive advanced ovarian cancer: analysis of KEYNOTE-028. Gynecol Oncol 2019;152:243–50.
Fan C (Ava), Reader J, Roque DM. Review of immune therapies targeting ovarian cancer. Curr Treat Options Oncol 2018;19:74.
Darb-Esfahani S, Kunze CA, Kulbe H, et al. Prognostic impact of programmed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) expression in cancer cells and tumorinfiltrating lymphocytes in ovarian high grade serous carcinoma. Oncotarget 2016;7:1486–99.
Webb JR, Milne K, Kroeger DR, et al. PD-L1 expression is associated with tumor-infiltrating T cells and favorable prognosis in high-grade serous ovarian cancer. Gynecol Oncol 2016;141:293–302.
Martin de la Fuente L, Westbom-Fremer S, Arildsen NS, et al. PD-1/PD-L1 expression and tumor-infiltrating lymphocytes are prognostically favorable in advanced high-grade serous ovarian carcinoma. Virchows Arch 2020;477:83–91.
Leskela S, Romero I, Cristobal E, et al. Mismatch repair deficiency in ovarian carcinoma: frequency, causes, and consequences. Am J Surg Pathol 2020;44:649–56.
Zibetti Dal Molin G, Abrahão CM, Coleman RL, et al. Response to pembrolizumab in a heavily treated patient with metastatic ovarian carcinosarcoma. Gynecol Oncol Res Pract 2018;5:6.
Bhangoo MS, Boasberg P, Mehta P, et al. Tumor mutational burden guides therapy in a treatment refractory POLE-mutant uterine carcinosarcoma. Oncologist 2018;23:518–23.
Friedman LA, Ring KL, Mills AM. LAG-3 and GAL-3 in endometrial carcinoma: emerging candidates for immunotherapy. Int J Gynecol Pathol 2020;39:203–12.
Moore M, Ring KL, Mills AM. TIM-3 in endometrial carcinomas: an immunotherapeutic target expressed by mismatch repair-deficient and intact cancers. Mod Pathol 2019;32:1168–79.
IH E. MHC class 1 and PDL-1 status of primary tumor and lymph node metastatic tumor tissue in gastric cancers. Gastroenterol Res Pract 2019;2019:4785098.
Perea F, Sánchez-Palencia A, Gómez-Morales M, et al. HLA class I loss and PD-L1 expression in lung cancer: impact on T-cell infiltration and immune escape. Oncotarget 2018;9:4120–33.
Friedrich M, Jasinski-Bergner S, Lazaridou MF, et al. Tumor-induced escape mechanisms and their association with resistance to checkpoint inhibitor therapy. Cancer Immunol Immunother 2019;68:1689–1700.