ER, PR: ER and PR are present in normal breast epithelial cells, and when cells become cancerous, ER and PR are partially or completely absent. If the ER and/or PR are still retained, the growth and proliferation of the breast cancer cells are still regulated by endocrine control, which is called hormone-dependent breast cancer; if the ER and/or PR are absent, the growth and proliferation of the breast cancer cells are no longer regulated by endocrine control, which is called non-hormone-dependent breast cancer.
C-erbB2 oncogene: It is lowly expressed in normal breast tissues, and its expression rate can be increased in breast cancer tissues. Its expression is positively correlated with breast cancer grade, lymph node metastasis and clinical stage, and the higher the expression rate, the worse the prognosis may be. p53 gene: Breast cancer cells with high p53 mutation rate have high proliferation vigor, poor differentiation, high malignancy, aggressiveness and high lymph node metastasis rate. p53 over overexpression suggests poor efficacy against third-generation aromatase inhibitors.
p63: p63 gene itself is an oncogene. p63 plays an important role in the occurrence and development of breast cancer; detection can provide the necessary theoretical basis for early diagnosis, timely treatment and prognosis of breast cancer.
p27: p27 oncogene, research shows that p27 is an independent prognostic marker of breast cancer. p27 low expression is associated with late TNM stage, lymph node metastasis, local recurrence and distant metastasis, and p27 low expression is significantly associated with short survival and poor prognosis. In this year’s ASCO meeting, a study by Porter et al. using tissue microarray technology showed that in breast cancer patients treated with AC regimen chemotherapy, p27 non-expression or low expression suggested poor prognosis in terms of OS and DFS.
COX-2 (cyclooxygenase-2): The expression of COX-2 in breast cancer tissues may be a useful indicator for clinical evaluation of patient prognosis and identification of patients at high risk of postoperative recurrence.
Ki-67: correlates with the prognosis of breast cancer, especially in patients with negative lymph node metastases, and helps to determine whether to use adjuvant chemotherapy.
E-cadherin: E-cadherin is a class of calcium-dependent transmembrane glycoproteins that establish tight junctions between cells, maintain cell polarity and keep tissue structure intact. E-cadherin expression or loss of function decreases the adhesion between cancer cells and neighboring cells, resulting in increased tumor cell activity and range, thus increasing the metastatic and infiltrative ability of cancer cells, which can be used as a prognostic indicator for breast cancer.
PS2: PS2 may be more useful than ER assay in predicting response to endocrine therapy, and PS2 expression is the best indicator of response to endocrine therapy in breast cancer.
Calponin: In the normal, hyperplastic and atypical hyperplasia groups of the breast, almost all myoepithelial cells expressed p63, α-SMA and Calponin, while all glandular epithelial cells were negative for the 3 antibodies; it is helpful to determine invasive carcinoma, carcinoma in situ and atypical hyperplasia.
CK : CK-L, CK8/18, CK7, CK20, CK34βE12 are cytokeratin (CK), EMA (Epithelial membrane antigen) is epithelial membrane antigen and CEA (carcinoembryonic antigen) is cytokine. carcinoembryonic antigen. These markers are often used in combination to detect, for example, tumors of epithelial origin, such as gastrointestinal tract tumors (esophageal cancer, gastric cancer, etc.), urological tumors (prostate cancer, kidney cancer, etc.), and gynecological tumors such as breast cancer. Since these indicators can detect many tumors with relatively low specificity, they should be combined with other examinations including medical history, physical examination and biopsy pathology to make a diagnosis, and we cannot rely on these indicators alone to confirm a certain tumor. However, the test results you mentioned have many positive results, suggesting the existence of tumor, and further examination is needed.
SMA (smooth muscle actin): Smooth muscle actin is a reliable marker antibody. The disappearance of ME is a gradual process from normal breast tissue, benign lesions to carcinoma in situ, early infiltration and infiltrative carcinoma.
EMA: Epithelial membrane antigen (EMA) is a group of high molecular weight glycoproteins, and its tissue distribution is generally limited to the luminal surface membrane of epithelial cells, and there is no EMA distribution on the basal and lateral cell membranes. EMA is not usually found in mesenchymal tumors, so EMA is a good marker of epithelial-derived tumors and can be used as one of the important indicators of lymph node micrometastasis in gastric cancer.
Laminin: Laminin mainly exists in the basal lamina structure and is a non-collagenous glycoprotein unique to the basal lamina, with a relative molecular mass of 820 kDa, containing 13-15% sugar, and three subunits, i.e. heavy chain (α chain, 400 kDa) and two light chains of β1 (215 kDa) and β2 (205 kDa). The structure shows an asymmetric cross shape, consisting of one long arm and three similar short arms. All four arms have rod-shaped segments and spherical terminal domains. β1 and β2 have two spherical domains on the short arm, and the short arm of the α chain has three spherical domains, one of which binds to type IV collagen, the second to heparin, and the other to cell surface receptors. It is these independent binding sites that allow LN to act as a bridge molecule that mediates cell binding to the basement membrane. The main function of LN is to act as a major structural component of the basement membrane, forming a network structure on the cell surface and anchoring the cell to the basement membrane.LN has many other roles, such as stimulating cell adhesion and cell motility during cell development.LN also stimulates neuraxis growth in the embryo and promotes regrowth and regeneration after neural injury in adult animals. LN is also a large glycoprotein that, together with type IV collagen, forms the basement membrane and is the earliest component of the extracellular matrix to appear in the developing embryo. The three short arms are each composed of the N-terminal sequences of three peptide chains. There are at least 8 cell binding sites in the LN molecule. For example, in the long arm near the spherical region. The chain contains the IKVAV pentapeptide sequence that binds to nerve cells and promotes nerve growth. The RGD sequence on the mouse LNα1 chain binds to αvβ3 integrins. Seven LN molecules with eight subunits (α1,α2,α3,β1,β2,β3,γ1,γ2) have been identified, and unlike FN, these eight subunits are encoded by eight structural genes. lN is a glycoprotein with high sugar content (15-28%), with about 50 N-linked glycan chains, and is the most complex glycoprotein with the most complex glycan chain structure known to date. Moreover, multiple receptors for LN are recognized and bound to its glycan structure.
Cyclin D1: High expression of Cyclin D1 may play an important role in the development and progression of human breast cancer. The clinical significance of high expression in breast cancer is that Cyclin D1 expression correlates with tumor size, TNM stage and axillary lymph node metastasis.
EGFR : Epithelial growth factor receptor (Epidermdl grouth factor receptor, EGFR) EGFR, like C-erdB-2, belongs to the same type I growth factor receptor family brigade. It is a tyrosine kinase receptor, mainly distributed in cell membranes. Under normal conditions, EGF is a potential mitogenic factor that can stimulate cell proliferation when it binds to target cell receptors. The cells surrounding the tumor are stimulated by the tumor cell secretory factor to start expressing EGFR, and the expression of EGFR gradually converts the “normal” surrounding cells to a malignant phenotype.
nm23: nm23, also known as an anti-metastatic oncogene, is an oncogene whose product is a 152 amino acid protein with a high degree of homology to the amino acid sequence of nucleoside diphosphate kinase (NDPK). The human nm23 gene has 2 isoforms: nm23H1 and nm23H2, which have 88% homology, and nm23H1 is more closely related to the prognosis of breast cancer. nm23 protein has NDPK function, regulates cell motility by affecting microtubule polymerization, and plays a negative regulatory role by affecting G protein signaling, thus inhibiting tumor metastasis. However, its action is not dependent on NDPK activity. Some experimental results suggest that it is the expression level of nm23NDPK rather than the activity of NDPK that is associated with metastatic potential. nm23 is an independent prognostic indicator, and its expression is independent of age, tumor size, ER, PR and C-erbB-2, and has a significant relationship with lymph node metastatic status, histological staging, grading and clinical stage. The prognosis of those with high nm23 expression is significantly better than that of those with low nm23 expression. breast cancers with reduced nm23 expression are less differentiated, have low ER expression levels, and often have lymph node metastasis with poor prognosis. During the progression of breast cancer, the expression level of nm23 decreases. The detection of nm23 can improve the outcome of treatment by screening out cases with potential distant metastasis in patients with positive axillary lymph nodes and potentially high metastatic tendency in patients with negative axillary lymph nodes for appropriate prophylactic treatment.
VEGF: vascular endothelial growth factor (VEGF) Angiogenesis plays a key role in tumor growth, infiltration and metastasis, which is regulated by a series of promoting and inhibiting factors, one of the most important promoting factors is VEGF secreted by tumor cells during growth, its coding gene is located at 6P21.3 and consists of 8 exons, due to the different shearing forms of mRNA Five different VEGFs are formed, containing 121, 145, 165, 189 and 206 amino acids, respectively, of which VEGF165 is the most important and predominantly expressed in various cells, VEGF121 and VEGF189 can be detected in most tissues and cells expressing VEGF, VEGF145 and VEGF206 are very rare, of which VEGF145 and VEGF206 are very rare, with VEGF206 only detectable in human fetal liver cDNA libraries. vEGF is active only when it forms a dimer through disulfide bonding, and its receptor is a tyrosine protein kinase-type membrane receptor with a high degree of specificity. VEGF is mainly produced by tumor cells, with a small proportion coming from the interstitial cells, and it is an independent prognostic indicator, independent of age and menopausal status. It is an independent prognostic indicator, independent of age and menopausal status, negatively correlated with ER and PR, and high VEGF expressers are prone to metastasis and recurrence with poor prognosis, and the effect of endocrine therapy and chemotherapy is poor. VEGF expression, etc., VEGF monoclonal antibodies Avastin and Elitecan.
It has been shown that circulating VEGF is a prognostic indicator, that those with high expression are prone to metastatic recurrence, and that this indicator can be used to guide treatment. In this year’s ASCO meeting, Ghosh et al. reported that VEGF expression was significantly higher in breast cancer tissues than in the stroma and correlated with several poor prognostic factors, with high expression suggesting poor prognosis at 20-year survival. Traina reported a study of letrozole + VEGF monoclonal antibody bevacizumab in patients with hormone receptor-positive metastatic breast cancer, in which VEGF was measured in tissues to guide treatment and to evaluate the correlation with outcome.
BRCA1: Basal cell-like breast cancers are a group of high-grade breast cancers with poor prognosis, and they typically present with ER, PR and HER-2 negative expression. The incidence is approximately 15-20% of all breast cancer patients and there is a strong association between incidence and BRCA1 gene mutations.
Bcl-2: Apoptosis suppressor genes include Bcl-2, Bcl-x1, Bcl-w, mcl-1, etc.; pro-apoptosis genes include Bcl-xs, Bax, Bad, Bak, Hrk and Bim. These two types of substances bind to each other and inhibit each other, and the relative amount of them often determines whether apoptosis occurs or not. Among the Bcl-2 family, Bcl-2 protein was the first to be identified and isolated, and so far it has been studied more thoroughly. Bcl-2 proteins play a key role in mediating the apoptotic pathway by regulating the translocation of substances inside and outside the nucleus involving endoplasmic reticulum Ca2+ and membrane permeability transition (PT) to prevent the release of cytochrome C from mitochondria, This prevents its interaction with Apaf-1 and procaspase-9, and ultimately inhibits the apoptotic cascade reaction triggered by Caspase-9 and Caspase-3. In conclusion, as an anti-apoptotic gene, Bcl-2 can protect cells from apoptosis induced by viruses, oxidants and other stimuli. Current studies suggest that high expression of Bcl-2 gene and its related proteins inhibit apoptosis as an important factor in tumorigenesis and drug resistance phenomenon.
CD44v6: CD44v6 is a transmembrane protein closely related to the invasive and metastatic behavior of cancer cells, mediating not only the adhesion of tumor cells to the extracellular matrix, but also participating in the interactions between tumor cells and between tumor cells and other cells. CD44v6, as a homing receptor for lymphocytes and a major receptor for hyaluronan, is able to connect to the extracellular matrix, bind to cytoskeletal proteins, and It is involved in the formation of cellular pseudopods, causing morphological and swimming changes in cells, and can be directly involved in the invasion and metastasis of tumor cells.
Pokemon: Pokemon is overexpressed in a variety of human tumors. Pokemon acts by specifically inhibiting the transcription of the tumor suppressor gene ARF, and cells lacking Pokemon gene do not respond to oncogenic transformation, thus this gene plays a critical role in tumorigenesis.
CD117: CD117 generally marks gastrointestinal mesenchymal tumors.
S-100: CgA(-), S-100, SyN(-) are neuroendocrine indicators. Negative indicates that it is not a neuroendocrine carcinoma. s-100 protein is an acidic calcium-binding protein with a molecular weight of 21 000, mainly found in the cytosol of astrocytes in various departments of the central nervous system, and is named because it is 100% soluble in saturated ammonium sulfate. s-100 protein consists of two subunits, α and β, in three different forms: S-100 ββ (S-100 b) is mainly found in glial cells and Schwann cells, S-100 αα (S-100 a0) is mainly found in glial cells, and S-100 αβ (S-100 a) is mainly found in transverse muscle, heart and kidney. It is generally believed that S-100 protein leaks out of the cytosol into the cerebrospinal fluid (CSF) when CNS cells are injured, and then enters the blood through the damaged blood-brain barrier. Therefore, increased S-100 protein in CSF and blood is a specific and sensitive biochemical marker of CNS injury.