MyD88 and TLR4 Expression in Epithelial Ovarian Cancer

Australian Ovarian Cancer Study Group

doi:10.1016/j.mayocp.2017.10.023

MyD88 and TLR4 Expression in Epithelial Ovarian Cancer

Australian Ovarian Cancer Study Group

Institut for Klinisk Medicin

14 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Tidsskrift	Mayo Clinic Proceedings
Vol/bind	93
Udgave nummer	3
Sider (fra-til)	307-320
Antal sider	14
ISSN	0025-6196
DOI	https://doi.org/10.1016/j.mayocp.2017.10.023
Status	Udgivet - 1 mar. 2018

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10.1016/j.mayocp.2017.10.023

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@article{b1c163db7e0348f78dfd79a2dda32526,

title = "MyD88 and TLR4 Expression in Epithelial Ovarian Cancer",

abstract = "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.",

keywords = "Adult, Aged, Biomarkers, Tumor/metabolism, Carcinoma, Ovarian Epithelial/metabolism, Female, Humans, Immunohistochemistry/methods, Middle Aged, Myeloid Differentiation Factor 88/metabolism, Ovarian Neoplasms/metabolism, Survival Analysis, Tissue Array Analysis/methods, Toll-Like Receptor 4/metabolism",

author = "Block, {Matthew S} and Vierkant, {Robert A} and Rambau, {Peter F} and Winham, {Stacey J} and Philipp Wagner and Nadia Traficante and Aleksandra To{\l}oczko and Tiezzi, {Daniel G} and Taran, {Florin Andrei} and Peter Sinn and Weiva Sieh and Raghwa Sharma and Rothstein, {Joseph H} and {Ram{\'o}n Y Cajal}, Teresa and Luis Paz-Ares and Oleg Oszurek and Sandra Orsulic and Ness, {Roberta B} and Gregg Nelson and Francesmary Modugno and Janusz Menkiszak and Valerie McGuire and McCauley, {Bryan M} and Marie Mack and Jan Lubi{\'n}ski and Longacre, {Teri A} and Zheng Li and Jenny Lester and Kennedy, {Catherine J} and Kalli, {Kimberly R} and Jung, {Audrey Y} and Johnatty, {Sharon E} and Mercedes Jimenez-Linan and Allan Jensen and Intermaggio, {Maria P} and Jillian Hung and Esther Herpel and Hernandez, {Brenda Y} and Hartkopf, {Andreas D} and Harnett, {Paul R} and Prafull Ghatage and Garc{\'i}a-Bueno, {Jos{\'e} M} and Bo Gao and Sian Fereday and Ursula Eilber and Edwards, {Robert P} and {de Sousa}, {Christiani B} and {de Andrade}, {Jurandyr M} and Kj{\ae}r, {Susanne K.} and Estrid H{\o}gdall and {Australian Ovarian Cancer Study Group}",

year = "2018",

month = mar,

day = "1",

doi = "10.1016/j.mayocp.2017.10.023",

language = "English",

volume = "93",

pages = "307--320",

journal = "Mayo Clinic Proceedings",

issn = "0025-6196",

publisher = "Elsevier",

number = "3",

}

TY - JOUR

T1 - MyD88 and TLR4 Expression in Epithelial Ovarian Cancer

AU - Block, Matthew S

AU - Vierkant, Robert A

AU - Rambau, Peter F

AU - Winham, Stacey J

AU - Wagner, Philipp

AU - Traficante, Nadia

AU - Tołoczko, Aleksandra

AU - Tiezzi, Daniel G

AU - Taran, Florin Andrei

AU - Sinn, Peter

AU - Sieh, Weiva

AU - Sharma, Raghwa

AU - Rothstein, Joseph H

AU - Ramón Y Cajal, Teresa

AU - Paz-Ares, Luis

AU - Oszurek, Oleg

AU - Orsulic, Sandra

AU - Ness, Roberta B

AU - Nelson, Gregg

AU - Modugno, Francesmary

AU - Menkiszak, Janusz

AU - McGuire, Valerie

AU - McCauley, Bryan M

AU - Mack, Marie

AU - Lubiński, Jan

AU - Longacre, Teri A

AU - Li, Zheng

AU - Lester, Jenny

AU - Kennedy, Catherine J

AU - Kalli, Kimberly R

AU - Jung, Audrey Y

AU - Johnatty, Sharon E

AU - Jimenez-Linan, Mercedes

AU - Jensen, Allan

AU - Intermaggio, Maria P

AU - Hung, Jillian

AU - Herpel, Esther

AU - Hernandez, Brenda Y

AU - Hartkopf, Andreas D

AU - Harnett, Paul R

AU - Ghatage, Prafull

AU - García-Bueno, José M

AU - Gao, Bo

AU - Fereday, Sian

AU - Eilber, Ursula

AU - Edwards, Robert P

AU - de Sousa, Christiani B

AU - de Andrade, Jurandyr M

AU - Kjær, Susanne K.

AU - Høgdall, Estrid

AU - Australian Ovarian Cancer Study Group

PY - 2018/3/1

Y1 - 2018/3/1

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Biomarkers, Tumor/metabolism

KW - Carcinoma, Ovarian Epithelial/metabolism

KW - Female

KW - Humans

KW - Immunohistochemistry/methods

KW - Middle Aged

KW - Myeloid Differentiation Factor 88/metabolism

KW - Ovarian Neoplasms/metabolism

KW - Survival Analysis

KW - Tissue Array Analysis/methods

KW - Toll-Like Receptor 4/metabolism

U2 - 10.1016/j.mayocp.2017.10.023

DO - 10.1016/j.mayocp.2017.10.023

M3 - Journal article

C2 - 29502561

SN - 0025-6196

VL - 93

SP - 307

EP - 320

JO - Mayo Clinic Proceedings

JF - Mayo Clinic Proceedings

IS - 3

ER -

MyD88 and TLR4 Expression in Epithelial Ovarian Cancer

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