Abstract
BackgroundTumour-infiltrating lymphocytes (TILs) have been demonstrated to significantly influence prognosis and response to therapy of invasive breast cancer (IBC). Thus, it has been suggested that TIL density or/and immunophenotype could serve as biomarkers for selection of IBC patients for immunotherapy. However, much less is known about significance of TILs in breast ductal carcinoma in situ (DCIS).MethodsWe retrospectively investigated TIL density and immunophenotype in 96 pure DCIS and 35 microinvasive carcinomas (miCa). TIL density was assessed on H&E-stained breast biopsy sections as the percentage of tumour stromal area occupied by TILs, and classified into 4 grades: 0 (0%–9%), 1 (10–29%), 2 (30–49%) and 3 (50%–100%). TIL immunophenotype was assessed by immunohistochemistry for CD8, CD4, FoxP3, CD38 or CD20.ResultsCompared to pure DCIS, miCa contained significantly more cases with TIL density grade 3 (p = 0.028). Concordantly, CD8+, CD4+ and CD38+ cells were more numerous in miCa than in pure DCIS. In the pure DCIS subgroup with TIL density grades 2 and 3, all TIL subpopulations were more numerous than in the pure DCIS with TIL density grades 0 and 1, however the ratio between T-lymphocytes (CD8+ and CD4+) and B-lymphocytes (CD20+) was significantly lower (p = 0.029). On the other side, this ratio was significantly higher in miCa, in comparison with pure DCIS having TIL density grades 2 and 3 (p = 0.017). By cluster analysis of tumour cell pathobiological features we demonstrated similarity between miCa and the pure DCIS with TIL density grades 2 and 3. The only significant difference between those two categories was in the ratio of T- to B-TILs, higher in miCa.ConclusionResults indicate that TIL density level can distinguish 2 biologically different DCIS subgroups, one of which (DCIS with ≥30% TILs, the TIL-rich DCIS) is like miCa. Similarity of TIL-rich pure DCIS and miCa as well as the role of B-lymphocytes in DCIS invasiveness are worth further investigating with regards to the potential development of immunotherapy-based prevention of DCIS progression.
Highlights
Tumour-infiltrating lymphocytes (TILs) have been demonstrated to significantly influence prognosis and response to therapy of invasive breast cancer (IBC)
We demonstrate that histological assessment of TILs can help recognizing a subcategory of pure ductal carcinoma in situ (DCIS) that is biologically very close to microinvasive carcinoma
In terms of TIL composition, microinvasive carcinomas (miCa) contained significantly more CD8+, CD4+ and CD38+ cells (p = 0.016, p = 0.001 and p = 0.024, respectively) whereas no statistically significant difference between DCIS and miCa was observed in the number of FoxP3+ or CD20+ cells
Summary
Tumour-infiltrating lymphocytes (TILs) have been demonstrated to significantly influence prognosis and response to therapy of invasive breast cancer (IBC). Clinical management of DCIS patients (pts) is still quite uniform, with many issues of debate, with regards to over- or undertreatment [3]. This situation is caused by a lack of reliable predictors of DCIS progression [4] and/or of molecular targets which could be therapeutically modulated to prevent occurrence of the invasive disease. It has been hypothesized that immunotherapies could prevent progression of the cancers in situ and even induce their rejection Such a treatment would be appealing to the patients with breast premalignant lesions, as the successful immunotherapies could reduce the rate of extensive surgeries and significantly improve patients’ quality of life
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