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. 2017 Jul 1;10(7):7743-7749.
eCollection 2017.

Differential Distribution of Immune Cells in Breast Invasive Carcinoma vs. Breast Carcinoma in situ and Its Significance in Interpretation of Immune Surveillance

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Free PMC article

Differential Distribution of Immune Cells in Breast Invasive Carcinoma vs. Breast Carcinoma in situ and Its Significance in Interpretation of Immune Surveillance

Li Wang et al. Int J Clin Exp Pathol. .
Free PMC article

Abstract

Immune surveillance is a highly controversial subject in both the field of immunology and cancer biology. On one hand, in spite of extensive studies, there is no cancer specific antigens identified. Yet, the organisms do exert immune response to tumors. On the other hand, it is believed that immune surveillance suppresses tumorigenesis by eradicating mutated cells. However, it is also widely known that tumorigenesis is promoted by inflammation, which is in nature immune reaction. In the present study, we tried to find immune cells in early tumor lesions for the supportive or negative evidence of immune surveillance. We used immunohistochemistry to observe the localization and distribution of immune cells in the in situ carcinoma lesions and in the invasive cancer of breast. Interestingly, we did not see immune cells in either ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS) of breast, the two basic supposed early cancer forms. In contrast, we observed extensive infiltration of immune cells in the invasive breast cancer, and close contact between immune cells and tumor cells. Based on these findings, we propose that the tumor antigens of breast cancer are not derived from the gene mutation or amplification such as HER2, but rather from misplacement of epithelial cells in the mesenchymal tissue. To avoid being targeted by the immune system, the carcinoma cells exert epithelial-mesenchymal transition (EMT). Therefore, immunosurveillance could be regarded as preventing the intrusion of epithelial cells to mesenchymal tissues, and EMT is a form of immune escape by the strategy of mimicry.

Keywords: Immunosurveillance; basement membrane; breast cancer; carcinoma in situ; epithelial mesenchymal transition.

Conflict of interest statement

None.

Figures

Figure 1
Figure 1
Immunohistochemistry revealing the immune cells in DCIS of breast. Immune cells cannot be seen inside the DCIS lesion of breast. Consecutive sections were stained for various markers. P63 was stained to reveal the existence of myoepithelial cells, a confirmative marker of DCIS. In these two cases of HER2 positive DCIS, no immune cells were seen inside the DCIS lesion. LCA, leukocyte common antigen; CD20, for B cells; CD3 for T cells; CD68 and CD163 for macrophages; CD57 for NK cells. There are immune cells stained in the stroma (*), which can be used as control. (A-F) is from one case, and (G-I) is from a separate case which is also HER2 positive.
Figure 2
Figure 2
Immunohistochemistry revealing the immune cells in LCIS of breast. A. HE staining shows the histology of the lesion. B. E-cadherin was stained to reveal the intercellular connections. The myoepithelial cells were positively stained but the luminal cells were all negative, which is a hallmark of LCIS. C-F. LCA, CD3, CD20 and CD68 were stained to reveal total and different types of immune cells. Note that there are not immune cells seen inside the LCIS lesion, but abundantly exist in the stroma.
Figure 3
Figure 3
Immunohistochemistry revealing the immune cells in invasive ductal carcinoma of breast. A. HE staining shows the histology. Small, round lymphocytes are seen in close contact with cancer cells. B-F. Are immunohistochemical staining with different markers for immune cells. LCA, leucocyte common antigen; CD3 for T cells, CD20 for B cells, CD68 for macrophages, and CD57 for NK cells.
Figure 4
Figure 4
Immunohistochemistry revealing the immune cells in invasive lobular carcinoma of breast. A. HE staining shows the histology. Cancer cells show a loose connection to each other. Inserts shows negative staining of e-cadherin. B-F. Are immunohistochemical staining with different markers for immune cells. LCA, leucocyte common antigen; CD3 for T cells, and CD20 for B cells, CD68 for macrophages, and CD57 for NK cells.
Figure 5
Figure 5
Leucocyte infiltration in CIN lesions and damage of epithelial basement membrane. (A) HE staining to show the histology of CIN lesion. (B) In a consecutive section of (A), immunohistochemical staining of LCA was done to reveal the existence of immune cells. (C-F) High power image with HE and PAS staining to show the damage of BM in CIN. (C and E) Are consecutive sections. The basement membrane was obviously damaged. (D and F) Are normal regions which were used to serve as control. Arrow heads points to the basement membrane.

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