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The ratio of CD8⁺/FOXP3 T lymphocytes infiltrating breast tissues predicts the relapse of ductal carcinoma in situ.

ABSTRACT: In a series of 248 tumor samples obtained from image-guided biopsies from patients diagnosed with ductal carcinoma in situ of the breast, we attempted to identify biomarkers that predict microinfiltration at definitive surgery or relapse during follow-up. For this, we used immunohistochemical methods, followed by automated image analyses, to measure the mean diameter of nuclei (which correlates with ploidy), the phosphorylation of eukaryotic initiation factor 2? (eIF2?, which reflects endoplasmic reticulum stress) as well as the density and ratio of CD8⁺ cytotoxic T lymphocytes and FOXP3⁺ regulatory T cells. The median nuclear diameter of malignant cells correlated with eIF2? phosphorylation (in cancerous tissue), which in turn correlated with the density of the CD8⁺ infiltrate and the CD8⁺/FOXP3 ratio (both in cancerous and the adjacent non-cancerous parenchyma). Neither microinfiltration nor lymph node involvement was associated with the probability of relapse. Both correlated positively with the CD8⁺/FOXP3 ratio in the malignant area. In contrast, relapse was associated with a paucity of the CD8⁺ infiltrate as well as an unfavorable CD8⁺/FOXP3 ratio, both in malignant and non-malignant parenchyma. The combined analysis of the CD8⁺/FOXP3 ratio in cancerous and non-cancerous tissues revealed a significant impact of their interaction on the probability of relapse, but not on the presence of microinfiltration or lymph node metastasis. Altogether, these results support the idea of an immunosurveillance system that determines the risk of relapse in ductal carcinoma in situ of the breast.

SUBMITTER: Semeraro M

PROVIDER: S-EPMC5087306 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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The ratio of CD8+/FOXP3 T lymphocytes infiltrating breast tissues predicts the relapse of ductal carcinoma in situ.

Semeraro Michaela M Adam Julien J Stoll Gautier G Louvet Emilie E Chaba Kariman K Poirier-Colame Vichnou V Sauvat Allan A Senovilla Laura L Vacchelli Erika E Bloy Norma N Humeau Juliette J Buque Aitziber A Kepp Oliver O Zitvogel Laurence L André Fabrice F Mathieu Marie-Christine MC Delaloge Suzette S Kroemer Guido G

Oncoimmunology 20160818 10

In a series of 248 tumor samples obtained from image-guided biopsies from patients diagnosed with ductal carcinoma in situ of the breast, we attempted to identify biomarkers that predict microinfiltration at definitive surgery or relapse during follow-up. For this, we used immunohistochemical methods, followed by automated image analyses, to measure the mean diameter of nuclei (which correlates with ploidy), the phosphorylation of eukaryotic initiation factor 2α (eIF2α, which reflects end ...[more]

PMID: 27853639

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Project description:Tumour-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).We 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.Compared 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.Results 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.

Dataset Information

The ratio of CD8⁺/FOXP3 T lymphocytes infiltrating breast tissues predicts the relapse of ductal carcinoma in situ.

Publications

The ratio of CD8<sup>+</sup>/FOXP3 T lymphocytes infiltrating breast tissues predicts the relapse of ductal carcinoma <i>in situ</i>.

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