Gastrointestinal mesenchymal tumor (GIST) is one of the tumors that differentiate from mesenchymal mesenchymal-derived cells, a type of cell with non-directional differentiation, i.e., with multiple differentiation potentials that can form smooth muscle (sarcoma), hemangioma (sarcoma), lipoma (sarcoma) neurofibroma, malignant nerve sheath tumor, etc., of which GIST is only one, non-lymphoid non-epithelial non-myogenic and non-neurogenic. Nevertheless, it is the type of mesenchymal-derived tumor (GIMT) that occupies the largest number. Although GIST has been widely used in pathology, many GISTs are underdiagnosed or misdiagnosed due to insufficient understanding in clinical practice, leading to failure of surgical treatment or inappropriate selection of chemotherapeutic agents, and the data cannot be effectively and accurately counted and analyzed for correlation. In this paper, we review the pathogenesis, pathological changes, immunological characteristics, treatment and prognosis of GIST. Origin and pathogenesis Pathological ultrastructural and immunohistochemical studies show that GIST is likely to originate from gastrointestinal Cahal cells. Evidence 1: Both have similar ultrastructure under electron microscopy, such as dendritic protrusions, clusters of dense core granules distributed near the protrusions or Golgi’s zone, incomplete or absent tumor cell substrates, and cytoplasmic regions with bridging granule-like junctions and interstitial filopodia-like fibers. Evidence 2: Cahal cells are the more specific cells expressing C-KIT gene protein in the gastrointestinal tract except for GIST cells. The C-KIT gene is a proto-oncogene that encodes a transmembrane protein with tyrosine kinase activity and a molecular weight of 117-145 kD. The protein receptor is regulated by stem cell factor (SCF), and SCF/KIT transmits extracellular signals to the cell via multiple signaling factors to initiate normal cell proliferation and differentiation or other gene expression. When the C-KIT gene is mutated, it fails to precisely regulate cell differentiation, proliferation and regulation of death, allowing more cells to enter the proliferative phase from the quiescent phase, which may be one of the key mechanisms causing the malignant transformation of GIST. The mutation rate at the 550-570 sites in the proximal membrane region of the inner region is 50-60% and is the main site of pathogenesis where malignant GIST can be detected. [2, 3] It is generally accepted that C-KIT gene mutation is an early event in the development of GIST, and C-KIT gene is closely associated with tumor invasion and metastasis, and homokaryon number, surgical cure rate and distant metastasis are independent prognostic factors of GIST. [PDGFRA is a platelet-derived growth factor receptor A, and its gene structure is similar to that of C-KIT gene, both belong to type III tyrosinase family, PDGFRA gene mainly shows exon 12 and 18 mutations, and the mutation rate is lower than that of C-KIT, which is mostly seen in PDGFRA mutations are associated with the site of mesenchymal tumor, mainly retroperitoneal and gastric-derived tumors. According to the identified GISTs, they can be divided into 3 categories according to genetic alterations: (1) C-KIT mutant (80%-85%); (2) PDGFRA mutant (5%-10%); (3) wild-type GIST (10%). There are roughly 3 types of genetic alterations, and they concluded that the most common one is the short arm 14, and the other is the long arm 1 and the short arm 22, and the alteration of the long arm 1 is related to the biological behavior of GIST and GIST in the small intestine site. [7] These different chromosomal abnormalities suggest that the formation of GIST is associated with mutations in genes other than C-KIT and PDGFRA. The immunomarker CD117 is the C-KIT gene product,CD117 is the most specific among several indicators for the diagnosis of GIST,and the positive rate can reach more than 85% [8].CD117 positivity is seen in benign and malignant GIST.In addition to its expression in GIST,CD117 is also seen in systemic lupus erythematosus,acute myocardial infarction,and epithelial malignancies.CD34 is a The analysis of the causes of GIST with negative CD117 expression may be related to the following factors: (1) the means of standardized detection of CD117 are not yet the same, and there are differences in immunopathological testing between different methods and ligand concentrations; (2) deletion of larger fragments of the C-KIT gene can affect CD34 is not expressed in true smooth muscle tumors and nerve sheath tumors, and CD34 can be present alone in CD117-negative GISTs, and for gastrointestinal tumors that are CD117-negative and CD34-positive or both, diagnosis is required by pathological features combined with C-KIT and PDGFRA gene test results. PDGFRA gene test results for diagnosis. P16 is a cell cycle protein-dependent kinase 4 inhibitor gene protein, which has a significant role in inhibiting proliferation and promoting apoptosis, and can affect the development of GIST. Schneider’s survival follow-up of 157 GIST patients found that P16 deletion, tumor necrosis and metastasis were independent prognostic factors of GIST, and P16-negative patients had significantly worse prognosis than P16-positive patients. prognosis, and the risk of mortality among relatives of the former with malignant disease with P16 deletion was 2.3 times higher than that of the latter. [P21WAF1 is a cell cycle-dependent kinase inhibitor, a tumor suppressor gene, which is lowly expressed in benign cases of GIST and highly expressed in malignant and potentially malignant GISTs, and its upregulation helps to inhibit tumor cell proliferation and induce apoptosis, a late event in GIST. scholars suggested that P21WAF1 could be one of the indicators to evaluate the malignant potential of GIST. [10] BCL-2 is an apoptosis inhibitory gene protein that induces tumor development through the inhibition of apoptosis in GIST tumor cells. both Ki-67 and PCNA reflect the rate of cell proliferation and growth and have some significance in determining the degree of benignity and malignancy and prognosis of GIST. nestin (neuroepithelial stem cell) is an Nestin (neuroepithelial stem cell) is an intermediate filament protein with a molecular weight of 210-240 KD. Studies have shown that Nestin is expressed in normal gastrointestinal cells, but also in primitive tumors derived from muscle and neural tissues, and gastrointestinal Cahal cells can also express Nestin. Nestin is expected to be a new GIST immunomarker. Bumming studied the expression of 12 different types of synaptic microbubble proteins in 41 GIST patients and concluded that the expression of synaptic microbubble proteins was associated with the malignancy, C He concluded that the expression of synaptic microbubble proteins was not related to the malignancy of GIST or to mutations in the C-KIT and PDGFRA genes, but this confirmed that GIST has a function in regulating neurotransmitter and hormone secretion. [12] Clinical classification According to Lewin (1992) and Emory (1999), GIST can be classified into three categories: (1) Frankly Malignant, with histologically confirmed metastases or infiltration into adjacent organs, or with two or more of (2) indicators; (2) Malignant Potential, with only one of the following indicators Potential), with only one of the following indicators: gastric GIST > 5.5 cm, intestinal GIST > 4 cm, nuclear division image of gastric > 5/50 HPF, intestinal > 1/50 HPF with tumor necrosis, obvious nuclear heterogeneity, abundant and dense cells, epithelial cells in the form of nests or glandular vesicles; (3) those who do not have the above indicators are benign. Treatment Surgery is the main treatment for GIST, and the prognosis is closely related to the first surgical treatment and complete resection. Except for some low-grade malignant tumors and elderly patients who opt for small-scale resection, most GISTs advocate complete resection of the tumor due to the chance of later recurrence, and the resection should include a sufficient amount of normal tissue margins. Large omental resection is advocated. In the process of resection, the tumor should not be turned randomly to avoid destroying the pseudocapsule and causing the tumor to spread. If the tumor spreads and implants during the surgery, the patient’s survival rate decreases significantly. For those who cannot completely clarify the pathological origin intraoperatively, intraoperative frozen biopsy should be performed if necessary for whole tumor biopsy. Since GIST rarely has lymph node metastasis, intraoperative lymph node dissection is of little significance. Laparoscopic resection treatment is suitable for tumors less than 5 cm in size. GISTs are generally not suitable for tumor removal. GISTs of the stomach with a diameter of < 3 cm can be locally resected or wedge resection with the cutting edge at least 3 cm from the tumor; 3-5 cm should be treated by wedge resection or major gastrectomy with the cutting edge at least 5 cm from the tumor; those with a diameter > 5 cm should be operated according to the scope of D2 clearance for gastric cancer. For rectal GISTs, especially for lower GISTs, surgical management is sometimes very difficult, because it is difficult to determine their malignancy before surgery. For patients with 5 cm diameter or recurrence, the choice should be made between anus preservation and enlargement surgery with full preoperative consultation. For those with local infiltration or distal metastasis, combined organ resection should be performed under the premise of radical treatment. For GIST with liver metastases, some Japanese scholars believe that a more complete resection of the invading liver lobe should be attempted, which is still the basic principle of treatment [13], but the author believes that it should be determined on a case-by-case basis. Although GIST itself is not sensitive to radiotherapy and general chemotherapeutic agents, most scholars still advocate relevant local treatment of metastases for tumors with liver metastases and abdominal metastases. Imatinib (code name STI571) is a molecularly targeted therapeutic agent that specifically inhibits tyrosine kinase receptors derived from C-KIT or PDGFRA, blocks cell signaling, and controls tumor cell growth and proliferation while inducing apoptosis, and is suitable for patients with inoperable and/or extensive metastases as well as for patients who have relapsed after surgery. By molecular genetic studies, STI571 was found to be equally sensitive to wild-type and mutant C-KIT, and the mutant type of the C-KIT gene occurring in exon 11 survived longer after treatment than mutations at several other loci [14]. STI571 can develop resistance in some patients during treatment, and early resistance may be associated with different types of gene mutations. It has been suggested that mutations in exon 9 of the C-KIT gene and in the D842V site of PDGFRA are more effective for early treatment of STI571, but also poorer survival throughout the post-treatment period, and that increasing the drug dose (from 400 mg to 800 mg) is effective for the type of exon 9 mutation in the C-KIT gene. [15] Late resistance occurs mainly in genes with exon 11 mutations in C-KIT, and these tumors can produce mutations in new sites, such as exons 13, 14, 17 and 18, which produce proteins that can override the tyrosine kinase ATP binding site, in addition to the activation of some signaling systems that transgress the C-KIT and PDGFRA genes, which are also important for late drug resistance. [16] Theou current study found that the presence of P-glycoprotein and multidrug resistance protein was detectable in most drug-resistant cases of GIST. [17]China approved the use of imatinib for the treatment of GIST from July 2003, the number of cases treated to do statistical analysis is still small, and there is insufficient information on the duration of use of imatinib treatment, adverse effects, and health economics evaluation, which needs to continue to be accumulated.Sunitinib is an anti-neovascular formation drug that interferes with the ability of tumor cells to develop new blood vessels. At the molecular level, it inhibits tyrosine kinase activity and consequently further prevents the growth of blood vessels. sunitinib is suitable for the treatment of cases resistant to STI571.