Abstract P3-07-56: Predictive value of tertiary lymphoid structure assessed by high endothelial venule count in neoadjuvant setting of triple-negative breast cancer
Authors: Song IH , Lee HJ , Park IA , Yu JH , Ahn J-H , Gong G 
Published: May 2016

Background

Tertiary lymphoid structure (TLS) is an ectopic lymph node-like structure characterized by lymphoid aggregation with high endothelial venules (HEVs), and is an important source of tumor-infiltrating lymphocytes (TILs). TILs have a strong prognostic and predictive significance, particularly in triple-negative breast cancer (TNBC). We previously analyzed expression of immune-related genes in pre-neoadjuvant chemotherapy (NAC) biopsy samples using NanoString assay and showed that gene expression of follicular helper T cell marker CXCL13, which is closely associated with TLSs, was an independent predictive factor for pathologic complete remission (pCR) in TNBC. However, measuring gene expression of biopsy sample is not easy to perform in daily pathology practice. Therefore, we evaluated TLSs by assessing hematoxylin and eosin (H&E) stained slides and immunohistochemistry, and investigated their clinical importance.

Methods

A total of 108 patients diagnosed with primary TNBC and treated with NAC (anthracycline, cyclophosphamide, and taxane) were included. The amounts of TILs and TLSs were histopathologically measured in H&E slides. Immunohistochemical studies were done in 55 cases with available tissue samples. The numbers of CD3-, CD8-, and CD20- immunopositive cells in tumor areas were counted by the image analyzer. MECA79- immunopositive HEV densities were calculated. Their relationship to CXCL13 gene expression by NanoString assay was also analyzed.

Results

The overall rate of pCR was 30.6% (33 of 108 tumors). Lower pre-NAC clinical T stage and higher level of TIL and TLS assessed by H&E slides were predictors of pCR in all cases. The mean number of MECA 79-immunopositive HEV in pre-NAC biopsy samples was 12 (range, 0-72). The amounts of TILs and TLSs, numbers of CD3-, CD8-, and CD20- positive cells, HEV density, and expression of CXCL13 showed good correlation with one another. Higher HEV density, CD20- positive cell number, and CXCL13 expression were predictors of pCR. Higher CD8- positive cell numbers and CXCL13 expression were associated with better disease-free survival rate.

Conclusion

The amount of TLSs assessed by H&E slides and MECA 79-immunopositive HEV densities was well correlated with level of TILs, numbers of CD3-, CD8-, and CD20-positive cells, and gene expression of CXCL13, and was significantly associated with pCR in TNBCs. Therefore, assessing HEV density by MECA 79 immunohistochemistry in pre-NAC biopsy samples might be an objective and valuable tool for predicting pCR of TNBC in routine pathology practice. Further investigation of mechanism of TLS development might help to improve immunotherapeutic strategy.

Citation Format: Song IH, Lee HJ, Park IA, Yu JH, Ahn J-H, Gong G. Predictive value of tertiary lymphoid structure assessed by high endothelial venule count in neoadjuvant setting of triple-negative breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-56.