B7-H3 and B7-H4 expression in phyllodes tumors of the breast detected by RNA in situ hybridization and immunohistochemistry: Association with clinicopathological features and T-cell infiltration

Phyllodes tumors are rare biphasic breast tumors with the potential for both local recurrence and distant metastasis. The aberrant expression of B7-H3 and B7-H4 B7 molecules could be potential targets for future development of immunotherapeutic approaches. This work was undertaken to evaluate the ex...

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Main Authors: Ga-Eon Kim, Nah Ihm Kim, Min Ho Park, Ji Shin Lee
Format: Article
Language:English
Published: SAGE Publishing 2018-11-01
Series:Tumor Biology
Online Access:https://doi.org/10.1177/1010428318815032
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author Ga-Eon Kim
Nah Ihm Kim
Min Ho Park
Ji Shin Lee
author_facet Ga-Eon Kim
Nah Ihm Kim
Min Ho Park
Ji Shin Lee
author_sort Ga-Eon Kim
collection DOAJ
description Phyllodes tumors are rare biphasic breast tumors with the potential for both local recurrence and distant metastasis. The aberrant expression of B7-H3 and B7-H4 B7 molecules could be potential targets for future development of immunotherapeutic approaches. This work was undertaken to evaluate the expression of B7-H3 and B7-H4 in phyllodes tumors and assess the association with the grade and clinical behavior of phyllodes tumors. In addition, the roles of B7-H3 and B7-H4 in the regulation of tumor immune surveillance were evaluated by assessing the relationship between B7-H3/B7-H4 expression and T-cell infiltration. The messenger RNA and protein expression of B7-H3/B7-H4 were determined by RNAscope in situ hybridization and immunohistochemistry, respectively, in 101 phyllodes tumors (60 benign, 26 borderline, and 15 malignant) using a tissue microarray. Immunohistochemistry for CD3 and CD8 was also performed. B7-H3 messenger RNA and protein appeared to be concentrated mainly in the stromal compartment of phyllodes tumors. However, B7-H4 messenger RNA and protein were undetectable in the stromal compartment of phyllodes tumors. Stromal B7-H3 messenger RNA and protein expression were noted in 10 (16.7%) and 31 (51.7%) of 60 benign phyllodes tumors, 12 (46.1%) and 20 (76.9%) of 26 borderline phyllodes tumors, and 10 (66.7%) and 13 (86.7%) of 15 malignant phyllodes tumors, respectively. Stromal B7-H3 messenger RNA and protein expression increased as phyllodes tumors progressed from benign to borderline and finally to the malignant grade (Pearson’s R  = 0.411, p  < 0.001 and Pearson’s R  = 0.293, p  = 0.003, respectively). The recurrence rate was higher in the stromal B7-H3 messenger RNA or protein-positive group than in the negative group, but this difference was not significant. Stromal B7-H3 protein expression inversely correlated with the densities of CD3 + and CD8 + T-cell infiltrates ( p  = 0.001 and p  = 0.027, respectively). These results suggest that B7-H3 is involved in the progression of phyllodes tumors and may contribute to their immune surveillance.
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spelling doaj-art-c0f13adfa1b24203be9903c88280eb102025-08-20T02:51:12ZengSAGE PublishingTumor Biology1423-03802018-11-014010.1177/1010428318815032B7-H3 and B7-H4 expression in phyllodes tumors of the breast detected by RNA in situ hybridization and immunohistochemistry: Association with clinicopathological features and T-cell infiltrationGa-Eon Kim0Nah Ihm Kim1Min Ho Park2Ji Shin Lee3Department of Pathology, Chonnam National University Medical School, Gwangju, South KoreaDepartment of Pathology, Chonnam National University Medical School, Gwangju, South KoreaDepartment of Pathology, Chonnam National University Medical School, Gwangju, South KoreaDepartment of Pathology, Chonnam National University Hwasun Hospital, Hwasun, South KoreaPhyllodes tumors are rare biphasic breast tumors with the potential for both local recurrence and distant metastasis. The aberrant expression of B7-H3 and B7-H4 B7 molecules could be potential targets for future development of immunotherapeutic approaches. This work was undertaken to evaluate the expression of B7-H3 and B7-H4 in phyllodes tumors and assess the association with the grade and clinical behavior of phyllodes tumors. In addition, the roles of B7-H3 and B7-H4 in the regulation of tumor immune surveillance were evaluated by assessing the relationship between B7-H3/B7-H4 expression and T-cell infiltration. The messenger RNA and protein expression of B7-H3/B7-H4 were determined by RNAscope in situ hybridization and immunohistochemistry, respectively, in 101 phyllodes tumors (60 benign, 26 borderline, and 15 malignant) using a tissue microarray. Immunohistochemistry for CD3 and CD8 was also performed. B7-H3 messenger RNA and protein appeared to be concentrated mainly in the stromal compartment of phyllodes tumors. However, B7-H4 messenger RNA and protein were undetectable in the stromal compartment of phyllodes tumors. Stromal B7-H3 messenger RNA and protein expression were noted in 10 (16.7%) and 31 (51.7%) of 60 benign phyllodes tumors, 12 (46.1%) and 20 (76.9%) of 26 borderline phyllodes tumors, and 10 (66.7%) and 13 (86.7%) of 15 malignant phyllodes tumors, respectively. Stromal B7-H3 messenger RNA and protein expression increased as phyllodes tumors progressed from benign to borderline and finally to the malignant grade (Pearson’s R  = 0.411, p  < 0.001 and Pearson’s R  = 0.293, p  = 0.003, respectively). The recurrence rate was higher in the stromal B7-H3 messenger RNA or protein-positive group than in the negative group, but this difference was not significant. Stromal B7-H3 protein expression inversely correlated with the densities of CD3 + and CD8 + T-cell infiltrates ( p  = 0.001 and p  = 0.027, respectively). These results suggest that B7-H3 is involved in the progression of phyllodes tumors and may contribute to their immune surveillance.https://doi.org/10.1177/1010428318815032
spellingShingle Ga-Eon Kim
Nah Ihm Kim
Min Ho Park
Ji Shin Lee
B7-H3 and B7-H4 expression in phyllodes tumors of the breast detected by RNA in situ hybridization and immunohistochemistry: Association with clinicopathological features and T-cell infiltration
Tumor Biology
title B7-H3 and B7-H4 expression in phyllodes tumors of the breast detected by RNA in situ hybridization and immunohistochemistry: Association with clinicopathological features and T-cell infiltration
title_full B7-H3 and B7-H4 expression in phyllodes tumors of the breast detected by RNA in situ hybridization and immunohistochemistry: Association with clinicopathological features and T-cell infiltration
title_fullStr B7-H3 and B7-H4 expression in phyllodes tumors of the breast detected by RNA in situ hybridization and immunohistochemistry: Association with clinicopathological features and T-cell infiltration
title_full_unstemmed B7-H3 and B7-H4 expression in phyllodes tumors of the breast detected by RNA in situ hybridization and immunohistochemistry: Association with clinicopathological features and T-cell infiltration
title_short B7-H3 and B7-H4 expression in phyllodes tumors of the breast detected by RNA in situ hybridization and immunohistochemistry: Association with clinicopathological features and T-cell infiltration
title_sort b7 h3 and b7 h4 expression in phyllodes tumors of the breast detected by rna in situ hybridization and immunohistochemistry association with clinicopathological features and t cell infiltration
url https://doi.org/10.1177/1010428318815032
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