Immunohistochemical techniques are playing an increasing role in tumor diagnosis and differential diagnosis and clinical guidance of drug use. Now, we will introduce the immunohistochemistry items commonly used in breast cancer one by one.
Immunohistochemistry is the study of localization, characterization and quantification of antigens (peptides and proteins) in tissue cells by applying the basic principle of immunology – antigen-antibody reaction, i.e., the principle of specific binding of antigen and antibody, through chemical reaction to make the color development of chromogenic agents (fluorescein, enzymes, metal ions, isotopes) that label antibodies.
Immunohistochemistry is generally expressed as positive and negative. Positive means that the cells or tissues are colored if they have the corresponding antigens, and negative means that they are not colored if they do not have the corresponding antigens.
Immunohistochemical techniques are playing an increasing role in tumor diagnosis and differential diagnosis and clinical guidance of drug use. Now, we will introduce each of the immunohistochemical items commonly used in breast cancer.
Epithelial membrane antigen (EMA)
EMA is a surface component of epithelial cells. Although it is not specific to the breast, it can be used in the diagnosis to differentiate breast cancer from non-epithelial tumors, and is especially helpful in the identification of malignant lymphoma from pleomorphic or spindle cell breast cancer suspected to be sarcoma. It is also useful for the identification of lymph nodes without EMA and bone marrow with microscopic metastases of breast cancer. EMA staining is also valuable for deciding whether it is a primary, or secondary, cancer of the breast. If it is negative, metastasis should be suspected.
Keratin (keratin)
Almost all breast cancers can show keratin, which is positive in ductal and lobular carcinomas and negative in fibroadenomas and lobular cystic sarcomas with spindle cells.
Contractile proteins
Myoepithelial cells contain high concentrations of contractile proteins, so they can be identified by antisera to actin or myosin. These antisera can be of value in differentiating sclerosing adenopathy rich in myoepithelium from tubular carcinoma, which usually lacks myoepithelium.
Basement membrane components
Immunohistochemical staining for Anti-lanminin and anti-collagen IV reveals intact basement membrane around the epithelium of normal breast, fibroadenoma, sclerosing adenopathy and epithelial proliferation, whereas the outline of intraductal carcinoma is poorly defined, and focal defects are seen in microscopic carcinoma infiltrates. Blood vessels also have basement membranes, so anti-collagen IV immunohistochemical staining helps to detect cancer cells that have invaded the blood vessels.
Endothelial markers
It is sometimes difficult to determine whether cancer cells in lymphatic vessels and blood vessels are artificial artifacts or infiltrations of their own. Since endothelial cells can be stained by coagulation factor VIII antiserum, they are of diagnostic value for cancer cells invaded by blood vessels.
Hormone receptors
Normal target cells contain specific receptors. In breast and breast cancer, there are estrogen receptors (ER), progesterone receptors (PR), prolactin receptors, and androgen receptors. Patients with positive ER and PR are generally considered to have the best outcome for endocrine therapy. The prognosis of ER-positive cases is better than negative ones, with high remission rate and low recurrence rate, while ER-negative cancers are poorly differentiated, aggressive and often tend to metastasize. Thus, ER testing is an important indicator to provide a judgment of patient prognosis.
Her-2 (human epidermal growth factor receptor-2)
HER2, also known as c-erB2, consists of 922 adenines, 1,382 cytosines, 1,346 guanines and 880 thymines. HER2 protein is a transmembrane protein with tyrosine protein kinase activity and is a member of the EGFR family.
The tumorigenic mechanism of HER2 oncogene is to inhibit apoptosis and promote proliferation; increase tumor cell invasiveness; and promote tumor vascularization and lymphovascular neoplasia. HER2 gene amplification is one of the most important factors affecting breast cancer growth and metastasis. HER2 gene overexpression can occur in approximately 30% of breast cancers and is associated with poorer patient prognosis. Currently, high Her-2 expression is considered as the primary target for Herceptin treatment.
The molecular typing of breast cancer based on the different biological markers of ER, PP, and Her-2 has been newly proposed. It is believed that ER- and PR-positive, Her-2-negative breast cancers come from the ductal epithelium of the breast and are generally better differentiated and sensitive to hormonal therapy, but most are insensitive to chemotherapy and have a better prognosis. ER- and PR-negative, Her-2-positive breast cancers come from the myoepithelium, the outer layer of the ducts of the breast, and are generally They are poorly differentiated and insensitive to hormonal therapy, but most of them are sensitive to chemotherapy and have a relatively poor prognosis. Breast cancers that are negative for all three are called “triple negative” breast cancers or basal-like cancers, which may be derived from myoepithelial or stem cells, have poor differentiation, high proliferative activity, early metastasis and poor prognosis. Only 15-20% of patients are sensitive to chemotherapy.
Ki-67
Ki-67 antigen is a nuclear antigen expressed in value-added cells discovered by Gerdes in 1983 and is currently the more certain marker of nuclear value-added, present in all phases of the cell cycle except the G0 phase. The expression of Ki-67 is important for evaluating the value-added status of cells, studying the biological behavior of tumors and judging their harmfulness.
P53
The wild-type P53 gene can inhibit cell transformation and suppress oncogene activity, while the mutant P53 gene can cause cell transformation and oncogenesis, resulting in unlimited cellular value-added. In breast cancer, the positive rate of P53 protein is 20-60%. mutation of P53 gene can upregulate endothelial factors that promote vascular proliferation, thus becoming an important factor in regulating blood vessel growth. And it is significantly correlated with lymph node metastasis caused by breast cancer.
Of course, P63, Ecadherin, CK5/6, etc. may also be applied in breast cancer research. Nowadays, breast cancer research is changing rapidly and various new methods are emerging. Such as PCR, RNA probes, fluorescence imaging techniques and so on. The field of research has entered the molecular level, and the targeting of drugs is becoming more and more powerful.