Article open access publication

MyD88 and TLR4 Expression in Epithelial Ovarian Cancer

Mayo Clinic Proceedings, Elsevier, ISSN 0025-6196

Volume 93, 3, 2018

DOI:10.1016/j.mayocp.2017.10.023, Dimensions: pub.1101297890, PMC: PMC5870793, PMID: 29502561,

Authors

Sharma, Raghwa (10) (11)
Paz-Ares, Luis (13) (14)
Li, Zheng (1) (21)
Hung, Jillian (22) (23)
Herpel, Esther (29) (30)
Harnett, Paul R. (23) (32)
Gao, Bo (23) (32)
Kjaer, Susanne K. (27) (40)
Huntsman, David G. (42) (43)
Høgdall, Estrid (27) (44)
Fasching, Peter A. (46) (47)
de Fazio, Anna (22) (23)
Deen, Suha (48)
Campbell, Ian G (5) (34)
Brenton, James D. (20) (50) (51)
Bowtell, David D L (5) (34) (52)
Benítez, Javier (14) (45)
Ramus, Susan J (28) (52)

* Corresponding author

Affiliations

Organisations

  1. (1) Mayo Clinic, grid.66875.3a
  2. (2) Catholic University of Health and Allied Sciences, grid.411961.a
  3. (3) University of Calgary, grid.22072.35
  4. (4) Universitätsklinikum Tübingen, grid.411544.1
  5. (5) University of Melbourne, grid.1008.9
  6. (6) Pomeranian Medical University, grid.107950.a
  7. (7) University of Sao Paulo, grid.11899.38
  8. (8) University Hospital Heidelberg, grid.5253.1
  9. (9) Icahn School of Medicine at Mount Sinai, grid.59734.3c
  10. (10) Pathology West ICPMR Westmead, Westmead Hospital, the University of Sydney, Sydney, Australia
  11. (11) Western Sydney University, grid.1029.a
  12. (12) Hospital de Sant Pau, grid.413396.a
  13. (13) Hospital Universitario 12 De Octubre, grid.144756.5
  14. (14) Spanish National Cancer Research Centre, grid.7719.8
  15. (15) Cedars-Sinai Medical Center, grid.50956.3f
  16. (16) The University of Texas Health Science Center at Houston, grid.267308.8
  17. (17) University of Pittsburgh Cancer Institute, grid.478063.e
  18. (18) University of Pittsburgh, grid.21925.3d
  19. (19) Stanford University, grid.168010.e
  20. (20) University of Cambridge, grid.5335.0
  21. (21) Yan'an Hospital Affiliated To Kunming Medical University, grid.452826.f
  22. (22) Westmead Hospital, grid.413252.3
  23. (23) University of Sydney, grid.1013.3
  24. (24) German Cancer Research Center, grid.7497.d
  25. (25) QIMR Berghofer Medical Research Institute, grid.1049.c
  26. (26) Addenbrooke's Hospital, grid.120073.7
  27. (27) Danish Cancer Society, grid.417390.8
  28. (28) UNSW Sydney, grid.1005.4
  29. (29) Heidelberg University, grid.7700.0
  30. (30) National Center for Tumor Diseases, grid.461742.2
  31. (31) University of Hawaii at Manoa, grid.410445.0
  32. (32) Crown Princess Mary Cancer Centre, Westmead Hospital, the University of Sydney, Sydney, Australia
  33. (33) Oncology Department, Hospital General de Albacete, Madrid, Spain
  34. (34) Peter MacCallum Cancer Centre, grid.1055.1
  35. (35) Hospital Universitario Fundación Jiménez Díaz, grid.419651.e
  36. (36) Royal Alexandra Hospital, grid.416087.c
  37. (37) Roswell Park Cancer Institute, grid.240614.5
  38. (38) University College London, grid.83440.3b
  39. (39) Alberta Health Services, grid.413574.0
  40. (40) Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  41. (41) Hollings Cancer Center, grid.467988.c
  42. (42) BC Cancer Agency, grid.248762.d
  43. (43) University of British Columbia, grid.17091.3e
  44. (44) University of Copenhagen, grid.5254.6, KU
  45. (45) Institute of Health Carlos III, grid.413448.e
  46. (46) David Geffen School of Medicine, Department of Medicine, Division of Hematology and Oncology, University of California at Los Angeles
  47. (47) University Hospital Erlangen, grid.411668.c
  48. (48) Queen's Medical Centre, grid.415598.4
  49. (49) University Cancer Center Hamburg, grid.412315.0
  50. (50) Cambridge Experimental Cancer Medicine Centre, Cambridge, UK
  51. (51) Cancer Research UK Cambridge Institute, grid.470869.4
  52. (52) Garvan Institute of Medical Research, grid.415306.5

Description

OBJECTIVE: To evaluate myeloid differentiation primary response gene 88 (MyD88) and Toll-like receptor 4 (TLR4) expression in relation to clinical features of epithelial ovarian cancer, histologic subtypes, and overall survival. PATIENTS AND METHODS: We conducted centralized immunohistochemical staining, semi-quantitative scoring, and survival analysis in 5263 patients participating in the Ovarian Tumor Tissue Analysis consortium. Patients were diagnosed between January 1, 1978, and December 31, 2014, including 2865 high-grade serous ovarian carcinomas (HGSOCs), with more than 12,000 person-years of follow-up time. Tissue microarrays were stained for MyD88 and TLR4, and staining intensity was classified using a 2-tiered system for each marker (weak vs strong). RESULTS: Expression of MyD88 and TLR4 was similar in all histotypes except clear cell ovarian cancer, which showed reduced expression compared with other histotypes (P<.001 for both). In HGSOC, strong MyD88 expression was modestly associated with shortened overall survival (hazard ratio [HR], 1.13; 95% CI, 1.01-1.26; P=.04) but was also associated with advanced stage (P<.001). The expression of TLR4 was not associated with survival. In low-grade serous ovarian cancer (LGSOC), strong expression of both MyD88 and TLR4 was associated with favorable survival (HR [95% CI], 0.49 [0.29-0.84] and 0.44 [0.21-0.89], respectively; P=.009 and P=.02, respectively). CONCLUSION: Results are consistent with an association between strong MyD88 staining and advanced stage and poorer survival in HGSOC and demonstrate correlation between strong MyD88 and TLR4 staining and improved survival in LGSOC, highlighting the biological differences between the 2 serous histotypes.

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2018: Realized

Research area: Medicine

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2018: Level 1

Research area: Medicine

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Times Cited: 11

Field Citation Ratio (FCR): 5.09

Relative Citation ratio (RCR): 1.38

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