Answer to the Teresa Pusiol comments to the paper “The association of tumor lymphocyte infiltration with clinico-pathological factor and survival in breast cancer” by Huszno et al.

Dear Editor,

Tumor-infiltrating lymphocytes became an interesting histopathologic element from 80-thies in the last century. Practically all tumors were studied especially in the light of the value of TILs according to therapy, prognosis and finally survival. A perfect review was presented by Manjili and coworkers [1], indicating the role of not only. It should be pointed out, that methods for TILs assessment in breast cancer vary in different studies, ranging from cell infiltrate counting on hematoxylin and eosin (HE) stained slides [2]; advanced immunohistochemical cell typing [3], gene expression in cellular infiltrations [4] and digital counting [6]. It should be pointed out, that method described by Roncati and coworkers [5] allows to easily simplification of TILs grading, diminishing the grade to 3 grades: absent TILs, so-called “non-brisk infiltrations” i.e. sparse and inactive TILs, and “brisk” infiltrations with abundant and active cells, offering clear statistical and clinical results. In our article [7] we used 4-grade TILs system, with an additional grade 1 – mild inflammatory infiltrate, similarly to a pooled analysis of four prospective adjuvant trials reported by Kotoula and coworkers [8] and many others. It should be expressed, that in our article we pooled two lowest grades (TILs 0-1) and two remaining (TILs 2-3) in statistical analysis. This step should offered the results similar to Roncati et al. observations [5] by pooling non-brisk and brisk infiltrations. Except that, we demonstrated that TILs status play a role together with HER2 status suggesting connection of these methods in breast cancer prognosis. According to Kotoula et al. [8] more advanced methods, including genetic panels should offer more precise prognoses.

References

1. Manjili MH, Najarian K, Wang XY. Signatures of tumor-immune interactions as biomarkers for breast cancer prognosis. Future Oncol 2012; 8: 703-711.
2. Loi S, Michiels S, Salgado R, et al. Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial. Ann Oncol 2014; 25: 1544-1550.
3. Rathore AS, Kumar S, Konwar R, et al. CD3+, CD4+ & CD8+ tumour infiltrating lymphocytes (TILs) are predictors of favourable survival outcome in infiltrating ductal carcinoma of breast. Indian J Med Res 2014; 140: 361-369.
4. Perez EA, Thompson EA, Ballman KV, et al. Genomic analysis reveals that immune function genes are strongly linked to clinical outcome in the north central cancer treatment group n9831 adjuvant trastuzumab trial. J Clin Oncol 2015; 33: 701-708.
5. Roncati L, Barbolini G, Piacentini F, et al. Prognostic Factors for Breast Cancer: an Immunomorphological Update. Pathol Oncol 2016; 22: 449-452.
6. Nawaz S, Heindl A, Koelble K, Yuan Y. Beyond immune density: critical role of spatial heterogeneity in estrogen receptor-negative breast cancer. Mod Pathol 2015; 28: 766-777.
7. Huszno J, Nożyńska EZ, Lange D, et al. The association of tumor lymphocyte infiltration with clinicopathological factors and survival in breast cancer. Pol J Pathol 2017; 68: 26-32.
8. Kotoula V, Chatzopoulos K, Lakis S, et al. Tumors with high-density tumor infiltrating lymphocytes constitute a favorable entity in breast cancer: a pooled analysis of four prospective adjuvant trials. Oncotarget 2016; 7: 5074-5087.