Analysis of tumour-infiltrating lymphocytes reveals two new biologically different subgroups of breast ductal carcinoma in situ
Abstract Background 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...
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| Format: | Article |
| Language: | English |
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BMC
2018-02-01
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| Series: | BMC Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s12885-018-4013-6 |
| _version_ | 1818291338245832704 |
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| author | Marie Beguinot Marie-Melanie Dauplat Fabrice Kwiatkowski Guillaume Lebouedec Lucie Tixier Christophe Pomel Frederique Penault-Llorca Nina Radosevic-Robin |
| author_facet | Marie Beguinot Marie-Melanie Dauplat Fabrice Kwiatkowski Guillaume Lebouedec Lucie Tixier Christophe Pomel Frederique Penault-Llorca Nina Radosevic-Robin |
| author_sort | Marie Beguinot |
| collection | DOAJ |
| description | Abstract Background 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). Methods 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. Results 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. Conclusion 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. |
| first_indexed | 2024-12-13T02:42:29Z |
| format | Article |
| id | doaj.art-c5ad628c979a4b1d90f99da8187ad503 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-13T02:42:29Z |
| publishDate | 2018-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-c5ad628c979a4b1d90f99da8187ad5032022-12-22T00:02:16ZengBMCBMC Cancer1471-24072018-02-0118111010.1186/s12885-018-4013-6Analysis of tumour-infiltrating lymphocytes reveals two new biologically different subgroups of breast ductal carcinoma in situMarie Beguinot0Marie-Melanie Dauplat1Fabrice Kwiatkowski2Guillaume Lebouedec3Lucie Tixier4Christophe Pomel5Frederique Penault-Llorca6Nina Radosevic-Robin7Department of Surgical Oncology, Jean Perrin Comprehensive Cancer CentreDepartment of Surgical Pathology and Biopathology, Jean Perrin Comprehensive Cancer CentreDepartment of Clinical Research, Jean Perrin Comprehensive Cancer CentreDepartment of Surgical Oncology, Jean Perrin Comprehensive Cancer CentreDepartment of Surgical Pathology and Biopathology, Jean Perrin Comprehensive Cancer CentreDepartment of Surgical Oncology, Jean Perrin Comprehensive Cancer CentreDepartment of Surgical Pathology and Biopathology, Jean Perrin Comprehensive Cancer CentreDepartment of Surgical Pathology and Biopathology, Jean Perrin Comprehensive Cancer CentreAbstract Background 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). Methods 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. Results 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. Conclusion 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.http://link.springer.com/article/10.1186/s12885-018-4013-6breastcancerductalin situmicroinvasivelymphocytes |
| spellingShingle | Marie Beguinot Marie-Melanie Dauplat Fabrice Kwiatkowski Guillaume Lebouedec Lucie Tixier Christophe Pomel Frederique Penault-Llorca Nina Radosevic-Robin Analysis of tumour-infiltrating lymphocytes reveals two new biologically different subgroups of breast ductal carcinoma in situ BMC Cancer breast cancer ductal in situ microinvasive lymphocytes |
| title | Analysis of tumour-infiltrating lymphocytes reveals two new biologically different subgroups of breast ductal carcinoma in situ |
| title_full | Analysis of tumour-infiltrating lymphocytes reveals two new biologically different subgroups of breast ductal carcinoma in situ |
| title_fullStr | Analysis of tumour-infiltrating lymphocytes reveals two new biologically different subgroups of breast ductal carcinoma in situ |
| title_full_unstemmed | Analysis of tumour-infiltrating lymphocytes reveals two new biologically different subgroups of breast ductal carcinoma in situ |
| title_short | Analysis of tumour-infiltrating lymphocytes reveals two new biologically different subgroups of breast ductal carcinoma in situ |
| title_sort | analysis of tumour infiltrating lymphocytes reveals two new biologically different subgroups of breast ductal carcinoma in situ |
| topic | breast cancer ductal in situ microinvasive lymphocytes |
| url | http://link.springer.com/article/10.1186/s12885-018-4013-6 |
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