Please use this identifier to cite or link to this item: https://doi.org/10.3389/fimmu.2018.01209
DC FieldValue
dc.titleHigh densities of tumor-associated plasma cells predict improved prognosis in triple negative breast cancer
dc.contributor.authorYeong J.
dc.contributor.authorLim J.C.T.
dc.contributor.authorLee B.
dc.contributor.authorLi H.
dc.contributor.authorChia N.
dc.contributor.authorOng C.C.H.
dc.contributor.authorLye W.K.
dc.contributor.authorPutti T.C.
dc.contributor.authorDent R.
dc.contributor.authorLim E.
dc.contributor.authorThike A.A.
dc.contributor.authorTan P.H.
dc.contributor.authorIqbal J.
dc.date.accessioned2019-03-22T08:39:33Z
dc.date.available2019-03-22T08:39:33Z
dc.date.issued2018
dc.identifier.citationYeong J., Lim J.C.T., Lee B., Li H., Chia N., Ong C.C.H., Lye W.K., Putti T.C., Dent R., Lim E., Thike A.A., Tan P.H., Iqbal J. (2018). High densities of tumor-associated plasma cells predict improved prognosis in triple negative breast cancer. Frontiers in Immunology 9 (MAY) : 1209. ScholarBank@NUS Repository. https://doi.org/10.3389/fimmu.2018.01209
dc.identifier.issn16643224
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/152591
dc.description.abstractBreast cancer is the most common malignancy affecting women, but the heterogeneity of the condition is a significant obstacle to effective treatment. Triple negative breast cancers (TNBCs) do not express HER2 or the receptors for estrogen or progesterone, and so often have a poor prognosis. Tumor-infiltrating T cells have been well-characterized in TNBC, and increased numbers are associated with better outcomes; however, the potential roles of B cells and plasma cells have been large. Here, we conducted a retrospective correlative study on the expression of B cell/plasma cell-related genes, and the abundance and localization of B cells and plasma cells within TNBCs, and clinical outcome. We analyzed 269 TNBC samples and used immunohistochemistry to quantify tumor-infiltrating B cells and plasma cells, coupled with NanoString measurement of expression of immunoglobulin metagenes. Multivariate analysis revealed that patients bearing TNBCs with above-median densities of CD38+ plasma cells had significantly better disease-free survival (DFS) (HR = 0.44; 95% CI 0.26-0.77; p = 0.004) but not overall survival (OS), after adjusting for the effects of known prognostic factors. In contrast, TNBCs with higher immunoglobulin gene expression exhibited improved prognosis (OS p = 0.029 and DFS p = 0.005). The presence of B cells and plasma cells was positively correlated (p < 0.0001, R = 0.558), while immunoglobulin gene IGKC, IGHM, and IGHG1 mRNA expression correlated specifically with the density of CD38+ plasma cells (IGKC p < 0.0001, R = 0.647; IGHM p < 0.0001, R = 0.580; IGHG1 p < 0.0001, R = 0.655). Interestingly, after adjusting the multivariate analysis for the effect of intratumoral CD38+ plasma cell density, the expression levels of all three genes lost significant prognostic value, suggesting a biologically important role of plasma cells. Last but not least, the addition of intratumoral CD38+ plasma cell density to clinicopathological features significantly increased the prognostic value for both DFS (?LR?2 = 17.28, p = 1.71E-08) and OS (?LR?2 = 10.03, p = 6.32E-08), compared to clinicopathological features alone. The best combination was achieved by integrating intratumoral CD38+ plasma cell density and IGHG1 which conferred the best added prognostic value for DFS (?LR?2 = 27.38, p = 5.22E-10) and OS (?LR?2 = 21.29, p = 1.03E-08). Our results demonstrate that the role of plasma cells in TNBC warrants further study to elucidate the relationship between their infiltration of tumors and disease recurrence. © 2018 Yeong, Lim, Lee, Li, Chia, Ong, Lye, Putti, Dent, Lim, Thike, Tan and Iqbal.
dc.publisherFrontiers Media S.A.
dc.sourceScopus
dc.subjectB cells; Immunohistochemistry; Plasma cells; Triple negative breast cancer; Tumor immunology
dc.typeArticle
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.contributor.departmentDEPT OF PATHOLOGY
dc.contributor.departmentDEPT OF MEDICINE
dc.description.doi10.3389/fimmu.2018.01209
dc.description.sourcetitleFrontiers in Immunology
dc.description.volume9
dc.description.issueMAY
dc.description.page1209
dc.published.statepublished
dc.grant.idSMPO201302
dc.grant.idNMRC/TA/0041/2015
dc.grant.idACP PATH BCS 14 001
dc.grant.fundingagencyA*STAR Biomedical Research Council (Singapore National Research Foundation)
dc.grant.fundingagencySingapore National Medical Research Council
dc.grant.fundingagencySingHealth Duke-NUS Pathology Academic Clinical Program Budding Clinician-Scientist
Appears in Collections:Elements
Staff Publications

Show simple item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
fimmu.2018.01209.pdf1.24 MBAdobe PDF

OPEN

NoneView/Download

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.