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Tumor microenvironment and its clinicopathological and prognostic associations in surgically resected cutaneous angiosarcoma

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Abstract

Purpose

Cutaneous angiosarcoma (CAS) is a rare but typically aggressive malignant vascular neoplasm of the skin. Tumor microenvironment (TME) of CAS and its associations with baseline clinicopathological features and patient outcomes are very important, especially when considering the recent advances in understanding of the tumor biology.

Methods/patients

We retrospectively reviewed medical records of patients who underwent surgical resection for CAS at a tertiary Hospital. The pretreated specimens were evaluated by immunohistochemistry for programmed cell death protein 1 (PD-1) and its ligand (PD-L1), densities of tumor infiltrative lymphocytes (TILs) (CD3+, CD4+, CD8+, CD45RO+, FoxP3+), as well as c-MYC and Ki-67 expressions. Overall survival (OS) was estimated by Kaplan–Meier method and compared with Log-rank test.

Results

A total of 21 CAS patients were identified. Median age was 67 (ranges: 20–81) years, 14 (66.7%) were male, and over 50% had lesions of scalp. Histopathological examination showed a predominantly spindle cell type (57.1%). All patients underwent surgery, 16 (76.2%) were treated further. PD-L1 was positively stained (> 1%) in tumor cells (42.9%) and TILs (23.8%). PD-1 expression (> 1%) was identified in TILs of 11 (52.4%) cases. PD-1/PD-L1 expressions were significantly associated with the higher densities of CD3+, CD4+, CD8+, CD45RO+, and Foxp3+ TILs, but not with patient characteristics or c-MYC or Ki-67 expression. Median OS was 18.5 months (95% CI 6.0–35.9), although no prognostic significance was observed with respect to any clinicopathological features.

Conclusion

We characterized TME and its clinical and prognostic association in CAS. PD-1/PD-L1 expressions were significantly associated with TILs subtypes but not with OS.

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References

  1. Antonescu C. Malignant vascular tumors—an update. Modern Pathol. 2014;27:S30–8 (Suppl 1).

    Article  CAS  Google Scholar 

  2. Dossett LA, Harrington M, Cruse CW, Gonzalez RJ. Cutaneous angiosarcoma. Curr Probl Cancer. 2015;39(4):258–63.

    Article  PubMed  Google Scholar 

  3. Bernstein JM, Irish JC, Brown DH, Goldstein D, Chung P, Razak ARA, et al. Survival outcomes for cutaneous angiosarcoma of the scalp versus face. Head Neck. 2017;39(6):1205–11.

    Article  PubMed  Google Scholar 

  4. Fujisawa Y, Yoshino K, Kadono T, Miyagawa T, Nakamura Y, Fujimoto M. Chemoradiotherapy with taxane is superior to conventional surgery and radiotherapy in the management of cutaneous angiosarcoma: a multicentre, retrospective study. Br J Dermatol. 2014;171(6):1493–500.

    Article  CAS  PubMed  Google Scholar 

  5. Perez MC, Padhya TA, Messina JL, Jackson RS, Gonzalez RJ, Bui MM, et al. Cutaneous angiosarcoma: a single-institution experience. Ann Surg Oncol. 2013;20(11):3391–7.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Florou V, Rosenberg AE, Wieder E, Komanduri KV, Kolonias D, Uduman M, et al. Angiosarcoma patients treated with immune checkpoint inhibitors: a case series of seven patients from a single institution. J Immunother Cancer. 2019;7(1):213.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Honda Y, Otsuka A, Ono S, Yamamoto Y, Seidel JA, Morita S, et al. Infiltration of PD-1-positive cells in combination with tumor site PD-L1 expression is a positive prognostic factor in cutaneous angiosarcoma. Oncoimmunology. 2017;6(1):e1253657.

    Article  PubMed  Google Scholar 

  8. Shimizu A, Kaira K, Okubo Y, Utsumi D, Yasuda M, Asao T, et al. Positive PD-L1 expression predicts worse outcome in cutaneous angiosarcoma. J Glob Oncol. 2017;3(4):360–9.

    Article  PubMed  Google Scholar 

  9. Kawamura A, Kawamura T, Riddell M, Hikita T, Yanagi T. Regulation of programmed cell death ligand 1 expression by atypical protein kinase C lambda/iota in cutaneous angiosarcoma. Cancer Sci. 2019;110(5):1780–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Bagaria SP, Gatalica Z, Maney T, Serie D, Parasramka M, Attia S, et al. Association between programmed death-ligand 1 expression and the vascular endothelial growth factor pathway in angiosarcoma. Front Oncol. 2018;8:71.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Botti G, Scognamiglio G, Marra L, Pizzolorusso A, Di Bonito M, De Cecio R, et al. Programmed death ligand 1 (PD-L1) expression in primary angiosarcoma. J Cancer. 2017;8(16):3166–72.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Fujii H, Arakawa A, Utsumi D, Sumiyoshi S, Yamamoto Y, Kitoh A, et al. CD8+ tumor-infiltrating lymphocytes at primary sites as a possible prognostic factor of cutaneous angiosarcoma. Int J Cancer. 2014;134(10):2393–402.

    Article  CAS  PubMed  Google Scholar 

  13. Gambichler T, Koim S, Wrobel M, Käfferlein HU, Brüning T, Stockfleth E, et al. Expression of programmed cell death proteins in Kaposi sarcoma and cutaneous angiosarcoma. J Immunother. 2020;43(5):169–74 (Hagerstown, Md: 1997).

    Article  CAS  PubMed  Google Scholar 

  14. Wollina U. Angiosarcoma: an immunogenic tumour. Br J Dermatol. 2018;179(2):257–8.

    PubMed  Google Scholar 

  15. Zhang ZY, Cheng YJ, Gong XL, Ge YP, Bai CM, Wang XJ, et al. Characteristics and outcomes of primary angiosarcoma. Zhonghua zhong liu za zhi [Chin J Oncol]. 2019;41(9):693–7.

    CAS  Google Scholar 

  16. Wang L, Lao IW, Yu L, Wang J. Clinicopathological features and prognostic factors in angiosarcoma: a retrospective analysis of 200 patients from a single Chinese medical institute. Oncol Lett. 2017;14(5):5370–8.

    PubMed  PubMed Central  Google Scholar 

  17. Magara T, Nakamura M, Oda T, Kato H, Morita A. Dynamic change of PD-L1 expression in cutaneous angiosarcoma. J Investig Dermatol. 2019;139(9):S302.

    Article  Google Scholar 

  18. Chang C, Wu SP, Hu K, Li Z, Schreiber D, Oliver J, et al. Patterns of care and survival of cutaneous angiosarcoma of the head and neck. Otolaryngology—Head Neck Surg. 2020;162(6):881–7.

    Article  Google Scholar 

  19. Oashi K, Namikawa K, Tsutsumida A, Takahashi A, Itami J, Igaki H, et al. Surgery with curative intent is associated with prolonged survival in patients with cutaneous angiosarcoma of the scalp and face—a retrospective study of 38 untreated cases in the Japanese population. Eur J Surg Oncol. 2018;44(6):823–9.

    Article  PubMed  Google Scholar 

  20. Chow TL, Kwan WW, Kwan CK. Treatment of cutaneous angiosarcoma of the scalp and face in Chinese patients: local experience at a regional hospital in Hong Kong. Hong Kong Med J Xianggang yi xue za zhi. 2018;24(1):25–31.

    CAS  PubMed  Google Scholar 

  21. Googe PB, Flores K, Jenkins F, Merritt B, Moschos SJ, Grilley-Olson JE. Immune checkpoint markers in superficial angiosarcomas: PD-L1, PD-1, CD8, LAG-3, and tumor-infiltrating lymphocytes. Am J Dermatopathol. 2020;43(8):556–559.

    Article  PubMed  Google Scholar 

  22. Orth MF, Buecklein VL, Kampmann E, Subklewe M, Noessner E, Cidre-Aranaz F, et al. A comparative view on the expression patterns of PD-L1 and PD-1 in soft tissue sarcomas. Cancer Immunol Immunother. 2020;69(7):1353–62.

    Article  CAS  PubMed  Google Scholar 

  23. Patel SH, Hayden RE, Hinni ML, Wong WW, Foote RL, Milani S, et al. Angiosarcoma of the scalp and face: the Mayo Clinic experience. JAMA Otolaryngol Head Neck Surg. 2015;141(4):335–40.

    Article  PubMed  Google Scholar 

  24. Buehler D, Rice SR, Moody JS, Rush P, Hafez GR, Attia S, et al. Angiosarcoma outcomes and prognostic factors: a 25-year single institution experience. Am J Clin Oncol. 2014;37(5):473–9.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Cassidy RJ, Switchenko JM, Yushak ML, Madden N, Khan MK, Monson DK, et al. The importance of surgery in scalp angiosarcomas. Surg Oncol. 2018;27(4):A3-a8.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Weidema ME, Flucke UE, Ho VKY, Hillebrandt-Roeffen MHS, Desar IME. Prognostic factors in a large nationwide cohort of histologically confirmed primary and secondary angiosarcomas. Cancers. 2019;11(11):1780.

    Article  PubMed Central  Google Scholar 

  27. Sinnamon AJ, Neuwirth MG, Mcmillan MT, Ecker BL, Karakousis GC. A prognostic model for resectable soft tissue and cutaneous angiosarcoma. J Surg Oncol. 2016;114(5):557–563.

    Article  PubMed  Google Scholar 

  28. Espejo-Freire AP, Elliott A, Rosenberg A, Costa PA, Barreto-Coelho P, Jonczak E, et al. Genomic landscape of angiosarcoma: a targeted and immunotherapy biomarker analysis. Cancers (Basel). 2021;13(19):4816.

    Article  CAS  Google Scholar 

  29. Sindhu S, Gimber LH, Cranmer L, McBride A, Kraft AS. Angiosarcoma treated successfully with anti-PD-1 therapy—a case report. J Immunother Cancer. 2017;5(1):58.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Xu F, Zheng J, Fu M, Zhou H. Antiprogrammed cell death protein 1 immunotherapy for angiosarcoma with high programmed death-ligand 1 expression: a case report. Immunotherapy. 2020;12(11):771–6.

    Article  CAS  PubMed  Google Scholar 

  31. Campanella NC, Penna V, Ribeiro G, Abrahão-Machado LF, Scapulatempo-Neto C, Reis RM. Absence of Microsatellite Instability In Soft Tissue Sarcomas. Pathobiology. 2015;82(1):36–42.

    Article  CAS  PubMed  Google Scholar 

  32. Casey SC, Tong L, Li Y, Do R, Walz S, Fitzgerald KN, et al. MYC regulates the antitumor immune response through CD47 and PD-L1. Science. 2016;352(6282):227–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Fraga-Guedes C, André S, Mastropasqua MG, Botteri E, Toesca A, Rocha RM, et al. Angiosarcoma and atypical vascular lesions of the breast: diagnostic and prognostic role of MYC gene amplification and protein expression. Breast Cancer Res Treat. 2015;151(1):131–40.

    Article  CAS  PubMed  Google Scholar 

  34. Requena C, Rubio L, Lavernia J, Machado I, Llombart B, Sanmartín O, et al. Immunohistochemical and fluorescence In situ hybridization analysis of MYC in a series of 17 cutaneous angiosarcomas: a single-center study. Am J Dermatopathol. 2018;40(5):349–54.

    Article  PubMed  Google Scholar 

  35. Manner J, Radlwimmer B, Hohenberger P, Mössinger K, Küffer S, Sauer C, et al. MYC high level gene amplification is a distinctive feature of angiosarcomas after irradiation or chronic lymphedema. Am J Pathol. 2010;176(1):34–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Mentzel T, Schildhaus HU, Palmedo G, Büttner R, Kutzner H. Postradiation cutaneous angiosarcoma after treatment of breast carcinoma is characterized by MYC amplification in contrast to atypical vascular lesions after radiotherapy and control cases: clinicopathological, immunohistochemical and molecular analysis of 66 cases. Modern Pathol. 2012;25(1):75–85.

    Article  CAS  Google Scholar 

  37. Shon W, Sukov WR, Jenkins SM, Folpe AL. MYC amplification and overexpression in primary cutaneous angiosarcoma: a fluorescence in-situ hybridization and immunohistochemical study. Modern Pathol. 2014;27(4):509–15.

    Article  CAS  Google Scholar 

  38. Donghi D, Kerl K, Dummer R, Schoenewolf N, Cozzio A. Cutaneous angiosarcoma: own experience over 13 years. Clinical features, disease course and immunohistochemical profile. J Eur Acad Dermatol Venereol. 2010;24(10):1230–4.

    Article  CAS  PubMed  Google Scholar 

  39. Kaira K, Shimizu A, Yasuda M, Ohkubo Y, Ishikawa O. PD-L1 expression and possibility of its therapeutic target in cutaneous angiosarcoma. J Clin Oncol. 2016;34:e23110-e (15_suppl).

    Article  Google Scholar 

  40. Adam J, Le Stang N, Rouquette I, Cazes A, Badoual C, Pinot-Roussel H, et al. Multicenter harmonization study for PD-L1 IHC testing in non-small-cell lung cancer. Ann Oncol. 2018;29(4):953–8.

    Article  CAS  PubMed  Google Scholar 

  41. Hirsch FR, McElhinny A, Stanforth D, Ranger-Moore J, Jansson M, Kulangara K, et al. PD-L1 immunohistochemistry assays for lung cancer: results from phase 1 of the blueprint PD-L1 IHC assay comparison project. J Thorac Oncol. 2017;12(2):208–22.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing, Dongcheng District, Beijing, 100730, China

    Y. Bi, X. Ren, J. Pang & Z. Liang

  2. Department of Dermatology, Beijing Tsinghua Changgung Hospital, School of Medicine, Tsinghua University, No. 168 Litang Road, Changping District, Beijing, 102218, China

    Y. Bi & Y. Zhao

  3. Department of Pathology, Weifang People’s Hospital, Weifang, 261041, China

    L. Ge

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Bi, Y., Ge, L., Ren, X. et al. Tumor microenvironment and its clinicopathological and prognostic associations in surgically resected cutaneous angiosarcoma. Clin Transl Oncol 24, 941–949 (2022). https://doi.org/10.1007/s12094-021-02744-0

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  • DOI: https://doi.org/10.1007/s12094-021-02744-0

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