MyD88 and TLR4 Expression in Epithelial Ovarian Cancer
Por:
Block, MS, Vierkant, RA, Rambau, PF, Winham, SJ, Wagner, P, Traficante, N, Toloczko, A, Tiezzi, DG, Taran, FA, Sinn, P, Sieh, W, Sharma, R, Rothstein, JH, Cajal, TY, Paz-Ares, L, Oszurek, O, Orsulic, S, Ness, RB, Nelson, G, Modugno, F, Menkiszak, J, McGuire, V, McCauley, BM, Mack, M, Lubinski, J, Longacre, TA, Li, Z, Lester, J, Kennedy, CJ, Kalli, KR, Jung, AY, Johnatty, SE, Jimenez-Linan, M, Jensen, A, Intermaggio, MP, Hung, J, Herpel, E, Hernandez, BY, Hartkopf, AD, Harnett, PR, Ghatage, P, Garcia-Bueno, JM, Gao, B, Fereday, S, Eilber, U, Edwards, RP, de Sousa, CB, de Andrade, JM, Chudecka-Glaz, A, Chenevix-Trench, G, Cazorla, A, Brucker, SY, Alsop, J, Whittemore, AS, Steed, H, Staebler, A, Moysich, KB, Menon, U, Koziak, JM, Kommoss, S, Kjaer, SK, Kelemen, LE, Karlan, BY, Huntsman, DG, Hogdall, E, Gronwald, J, Goodman, MT, Gilks, B, Garcia, MJ, Fasching, PA, de Fazio, A, Deen, S, Chang-Claude, J, dos Reis, FJC, Campbell, IG, Brenton, JD, Bowtell, DD, Benitez, J, Pharoah, PDP, Kobel, M, Ramus, SJ, Goode, EL
Publicada:
1 mar 2018
Resumen:
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. (C) 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc.
Filiaciones:
Block, MS:
Mayo Clin, Dept Med Oncol, Rochester, MN USA
Vierkant, RA:
Mayo Clin, Dept Hlth Sci Res, 200 First St SW, Rochester, MN 55905 USA
Rambau, PF:
Univ Calgary, Dept Pathol, Calgary, AB, Canada
Univ Calgary, Lab Med, Calgary, AB, Canada
Catholic Univ Hlth & Allied Sci Bugando, Pathol Dept, Mwanza, Tanzania
Winham, SJ:
Mayo Clin, Dept Hlth Sci Res, 200 First St SW, Rochester, MN 55905 USA
Wagner, P:
Tubingen Univ Hosp, Dept Womens Hlth, Tubingen, Germany
Traficante, N:
Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic, Australia
Toloczko, A:
Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland
Tiezzi, DG:
Univ Sao Paulo, Gynecol & Obstet Ribeirao Preto Med Sch, Ribeirao Preto, Brazil
Taran, FA:
Tubingen Univ Hosp, Dept Womens Hlth, Tubingen, Germany
Sinn, P:
Heidelberg Univ Hosp, Inst Pathol, Dept Pathol, Heidelberg, Germany
Sieh, W:
Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, Dept Populat Hlth Sci & Policy, New York, NY 10029 USA
Sharma, R:
Univ Sydney, Westmead Hosp, Pathol West ICPMR Westmead, Sydney, NSW, Australia
Univ Western Sydney, Westmead Hosp, Westmead, NSW, Australia
Rothstein, JH:
Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, Dept Populat Hlth Sci & Policy, New York, NY 10029 USA
Cajal, TY:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Paz-Ares, L:
H12O CNIO Lung Canc Clin Res Unit, Madrid, Spain
Hosp Univ 12 Octubre, Oncol Dept, Madrid, Spain
Oszurek, O:
Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland
Orsulic, S:
Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA
Ness, RB:
Univ Texas Houston, Sch Publ Hlth, Houston, TX USA
Nelson, G:
Univ Calgary, Cumming Sch Med, Div Gynecol Oncol, Dept Oncol, Calgary, AB, Canada
Modugno, F:
Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA
Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA
Magee Womens Res Inst, Womens Canc Res Program, Pittsburgh, PA USA
Univ Pittsburgh, Canc Inst, Pittsburgh, PA USA
Menkiszak, J:
Pomeranian Med Univ, Dept Gynecol Surg & Gynecol Oncol, Adults & Adolescents, Szczecin, Poland
McGuire, V:
Staffordshire Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA USA
McCauley, BM:
Mayo Clin, Dept Hlth Sci Res, 200 First St SW, Rochester, MN 55905 USA
Mack, M:
Univ Cambridge, Dept Oncol, Strangeways Res Lab, Cambridge, England
Lubinski, J:
Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland
Longacre, TA:
Stanford Univ, Dept Pathol, Stanford, CA USA
Li, Z:
Mayo Clin, Dept Hlth Sci Res, 200 First St SW, Rochester, MN 55905 USA
Kunming Med Univ, Yunnan Tumor Hosp, Affiliated Hosp 3, Dept Gynecol Oncol, Kunming, Yunnan, Peoples R China
Lester, J:
Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA
Kennedy, CJ:
Univ Sydney, Westmead Inst Med Res, Ctr Canc Res, Sydney, NSW, Australia
Westmead Hosp, Dept Gynaecol Oncol, Sydney, NSW, Australia
Kalli, KR:
Mayo Clin, Dept Med Oncol, Rochester, MN USA
Jung, AY:
Deutsch Krebsforschungszentrum, German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany
Johnatty, SE:
QIMR Berghofer Med Res Inst, Dept Genet, Brisbane, Qld, Australia
Jimenez-Linan, M:
Addenbrookes Hosp, Dept Histopathol, Cambridge, England
Jensen, A:
Danish Canc Soc Res Ctr, Lifestyle & Genes, Virus, Copenhagen, Denmark
Intermaggio, MP:
Univ New South Wales, Sch Womens & Childrens Hlth, Sydney, NSW, Australia
Hung, J:
Univ Sydney, Westmead Inst Med Res, Ctr Canc Res, Sydney, NSW, Australia
Westmead Hosp, Dept Gynaecol Oncol, Sydney, NSW, Australia
Herpel, E:
Natl Ctr Tumor Dis NCT, Tissue Bank, Heidelberg, Germany
Heidelberg Univ, Inst Pathol, Heidelberg, Germany
Hernandez, BY:
Univ Hawaii, Canc Ctr, Honolulu, HI 96822 USA
Hartkopf, AD:
Tubingen Univ Hosp, Dept Womens Hlth, Tubingen, Germany
Harnett, PR:
Univ Sydney, Westmead Inst Med Res, Ctr Canc Res, Sydney, NSW, Australia
Univ Sydney, Westmead Hosp, Crown Princess Mary Canc Ctr, Sydney, NSW, Australia
Ghatage, P:
Univ Calgary, Cumming Sch Med, Div Gynecol Oncol, Dept Oncol, Calgary, AB, Canada
Garcia-Bueno, JM:
Hosp Gen Albacete, Oncol Dept, Madrid, Spain
Gao, B:
Univ Sydney, Westmead Inst Med Res, Ctr Canc Res, Sydney, NSW, Australia
Univ Sydney, Westmead Hosp, Crown Princess Mary Canc Ctr, Sydney, NSW, Australia
Fereday, S:
Peter MacCallum Canc Ctr, Dept Canc Genom & Genet, East Melbourne, Vic, Australia
Eilber, U:
Deutsch Krebsforschungszentrum, German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany
Edwards, RP:
Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA
de Sousa, CB:
Univ Sao Paulo, Gynecol & Obstet Ribeirao Preto Med Sch, Ribeirao Preto, Brazil
de Andrade, JM:
Univ Sao Paulo, Gynecol & Obstet Ribeirao Preto Med Sch, Ribeirao Preto, Brazil
Chudecka-Glaz, A:
Pomeranian Med Univ, Dept Gynecol Surg & Gynecol Oncol, Adults & Adolescents, Szczecin, Poland
Chenevix-Trench, G:
QIMR Berghofer Med Res Inst, Dept Genet, Brisbane, Qld, Australia
Cazorla, A:
Fdn Jimenez Diaz, Pathol Dept, Madrid, Spain
Brucker, SY:
Tubingen Univ Hosp, Dept Womens Hlth, Tubingen, Germany
Alsop, J:
Univ Cambridge, Dept Oncol, Strangeways Res Lab, Cambridge, England
Whittemore, AS:
Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA USA
Stanford Univ, Sch Med, Dept Biomed Data Sci, Stanford, CA USA
Steed, H:
Royal Alexandra Hosp, Div Gynecol Oncol, Dept Obstet & Gynecol, Edmonton, AB, Canada
Staebler, A:
Tubingen Univ Hosp, Inst Pathol, Tubingen, Germany
Moysich, KB:
Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA
Menon, U:
UCL, Inst Womens Hlth, Dept Womens Canc, Gynaecol Canc Res Ctr, London, England
Koziak, JM:
Alberta Hlth Serv Canc Care, Calgary, AB, Canada
Kommoss, S:
Tubingen Univ Hosp, Dept Womens Hlth, Tubingen, Germany
Kjaer, SK:
Danish Canc Soc Res Ctr, Lifestyle & Genes, Virus, Copenhagen, Denmark
Univ Copenhagen, Rigshosp, Dept Gynecol, Copenhagen, Denmark
Kelemen, LE:
Med Univ South Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA
Hollings Canc Ctr, Charleston, SC USA
Karlan, BY:
Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA
Huntsman, DG:
Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC, Canada
British Columbia Canc Agcy, Ctr Translat & Appl Gen, Vancouver, BC, Canada
Hogdall, E:
Univ Copenhagen, Herlev Hosp, Dept Pathol, Mol Unit, Copenhagen, Denmark
Gronwald, J:
Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland
Goodman, MT:
Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA
Gilks, B:
Vancouver Gen Hosp, Genet Pathol Evaluat Ctr, Vancouver, BC, Canada
Univ British Columbia, Vancouver, BC, Canada
Garcia, MJ:
Ctr Nacl Invest Oncol, Spanish Natl Canc Res Ctr, Human Genet Grp, Madrid, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Raras, Ctr Biomed Network Res Rare Dis, Madrid, Spain
Fasching, PA:
Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA
Univ Hosp Erlangen, Univ Breast Ctr Franconia, Dept Gynecol & Obstet, Erlangen, Germany
de Fazio, A:
Univ Sydney, Westmead Inst Med Res, Ctr Canc Res, Sydney, NSW, Australia
Westmead Hosp, Dept Gynaecol Oncol, Sydney, NSW, Australia
Deen, S:
Nottingham Univ Hosp NHS Trust, Queens Med Ctr, Dept Histopathol, Nottingham, England
Chang-Claude, J:
Deutsch Krebsforschungszentrum, German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany
Univ Med Ctr Hamburg Eppendorf, Univ Canc Ctr Hamburg, Hamburg, Germany
dos Reis, FJC:
Univ Sao Paulo, Gynecol & Obstet Ribeirao Preto Med Sch, Ribeirao Preto, Brazil
Campbell, IG:
Peter MacCallum Canc Ctr, Res Div, Canc Genet Lab, Melbourne, Vic, Australia
Univ Melbourne, Dept Oncol, Sir Peter MacCallum, Melbourne, Vic, Australia
Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia
Brenton, JD:
Univ Cambridge, Dept Oncol, Hutchison MRC Res Ctr, Cambridge, England
Univ Cambridge, Li Ka Shing Ctr, Canc Res UK Cambridge Inst, Cambridge, England
Cambridge Expt Canc Med Ctr, Cambridge, England
Bowtell, DD:
Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic, Australia
Peter MacCallum Canc Ctr, Res Dept, Canc Genom Program, East Melbourne, Vic, Australia
Garvan Inst, Sydney, NSW, Australia
Benitez, J:
Ctr Nacl Invest Oncol, Spanish Natl Canc Res Ctr, Human Genet Grp, Madrid, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Raras, Ctr Biomed Network Res Rare Dis, Madrid, Spain
Pharoah, PDP:
Univ Cambridge, Dept Oncol, Strangeways Res Lab, Cambridge, England
Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge, England
Kobel, M:
Univ Calgary, Dept Pathol, Calgary, AB, Canada
Univ Calgary, Lab Med, Calgary, AB, Canada
Ramus, SJ:
Univ New South Wales, Sch Womens & Childrens Hlth, Sydney, NSW, Australia
Garvan Inst, Sydney, NSW, Australia
Goode, EL:
Mayo Clin, Dept Hlth Sci Res, 200 First St SW, Rochester, MN 55905 USA
Green Published, Green Accepted, hybrid
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