Tumor infiltrating leukocyte density is independent of tumor grade and molecular subtype in aggressive breast cancer of Western Kenya

Abstract

BackgroundTumors commonly are infiltrated by leukocytes, or tumor infiltrating leukocytes (TILs). It remains unclear, however, if the density and type of individual TILs has a direct or simply correlative role in promoting poor prognosis in breast cancer patients. Breast cancer in Kenyan women is aggressive with presentation at a young age, with advanced grade (grade III), large tumor size (>2.0 cm), and poor prognosis. We previously observed that the tumors were predominantly estrogen receptor positive (ER+) but also included both a high percentage of triple negative tumors and also increased immune cell infiltration within the tumors. We used breast tumor tissues from each patient to make tissue microarrays that were then stained for leukocyte and myeloid markers including CD4, CD8, CD20, CD25, CD68, and CD163 using immunohistochemical techniques. The immune cell infiltration into the cancer tissue included increased numbers of macrophages (CD68+), helper T cells (CD4+), and CD25+ lymphocytes compared to benign tissue.ResultsThis study characterized the grade, molecular subtypes, and proliferation index of these tumors and determined if TIL density was enriched across any of these factors. We analyzed 49 malignant patient tissue samples for this study. The patient population had a mean age of 51.9 years. The tumors analyzed were heterogeneous by grade: grade I (6%), grade II (47%), and grade III (39%). Most patients presented with large tumors (>2.0 cm) (69%). We classified the tumors into molecular subtypes based on clinical marker expression. Based on this analysis, the molecular subtype distribution was heterogeneous with luminal B (41%), basal/triple negative (TN) (37%), luminal A (14%) and HER2 (8%) breast cancer subtypes. While the basal/TN subtype had a much higher proliferative index (Ki-67+) than did the other molecular subtypes, we did not see a significant correlation between TIL density and either subtype or tumor grade. Therefore, TIL density is independent of molecular subtype and grade.ConclusionThis study identified a Kenyan patient cohort that develops large, high-grade tumors primarily of the luminal B and basal molecular subtypes. After analyzing the TILs within these tumors, we found that immune cell infiltration of these tumors correlated with increased proliferation but not grade or molecular subtype. Future research is required to determine if the aberrant recruitment of TILs to tumors contributes to cancer progression and response to cancer treatments.

Stromal Tumor Infiltrating Lymphocytes (sTILs) as a putative prognostic marker to identify a responsive subset of TNBC in an Indian Breast Cancer Cohort

“…Average sTILs scores show even distribution across age, menopausal status, and lymph node status. Tumor grade and tumor size (cT and pT) show significantly skewed sTILs distribution where higher grade and larger size tumors are associated with higher sTILs percentages 26–28 .…”

The distribution of reproductive risk factors disclosed the heterogeneity of receptor-defined breast cancer subtypes among Tanzanian women

“…However, our findings differ from many African studies, as summarized in Additional file 1 : Table S2. Most African studies show that triple-negative ranks the first or the second most prevalent subtype among women diagnosed with BC [ 29 ]. Triple-negative tumors are aggressive, younger age at diagnosis, and are most frequently seen in BC patients of African ancestry [ 30 ].…”

In situ immunopathological events in human cervical intraepithelial neoplasia and cervical cancer: Review

“…Tumors commonly are infiltrated by leukocytes. The immune cell infiltration into the cancer tissue included increased numbers of monocyte/macrophages, helper T cells (CD4+), and CD25+ lymphocytes compared to benign tissue [128] . Chemokines are cytokines which induce chemotaxis on many cell types which play a crucial role in inflammatory processes and in tumor associated angiogenesis, as well as in tumor progression.…”