Thyroid cancer

Description: Thyroid carcinoma is the most common thyroid malignancy. It is a malignant tumor derived from thyroid epithelial cells. Most thyroid cancers originate from follicular epithelial cells and can be classified into papillary carcinoma according to pathological type (60%). ), follicular adenocarcinoma (20%), but the prognosis is better; follicular adenocarcinoma tumors grow faster, moderately malignant, easy to pass blood transport; undifferentiated cancer has a poor prognosis, the average survival time is 3 ~ 6 months. Papillary carcinoma is more common in thyroid cancer. Causes: (1) Causes of disease 1. Iodine and thyroid cancer iodine is an essential trace element in human body. It is generally believed that iodine deficiency is endemic goiter, iodine deficiency leads to decreased synthesis of thyroid hormone, and thyroid stimulating hormone (TSH) level is increased. Thyroid follicular hyperplasia, thyroid enlargement, thyroid hormone, increase the incidence of thyroid cancer, the current opinion is not consistent, but mostly follicular thyroid cancer, not the most common pathological type of thyroid cancer - papillary thyroid cancer, In the endemic goiter area, thyroid papillary carcinoma accounts for 85% of well-differentiated thyroid cancer. There is no significant change in the incidence of thyroid cancer before and after iodized salt prevention. The proportion of thyroid papillary carcinoma after effective iodized salt prevention Increased, high intake of foods containing high levels of iodine, high iodine diet may increase the incidence of papillary thyroid cancer. 2. Radiation and thyroid cancer X-ray irradiation of the thyroid gland of the experimental mouse can promote thyroid cancer in the animal, the nuclear deformation, the synthesis of thyroxine is greatly reduced, leading to cancer; on the other hand, the thyroid gland is destroyed and no endocrine is produced. The massive secretion of thyroid stimulating hormone (TSH) can also trigger thyroid cell carcinogenesis. In clinical practice, many facts indicate that the occurrence of thyroid is related to the role of radiation. Children who have undergone upper mediastinal or cervical radiation therapy due to thymic enlargement or lymphoid adenoid proliferation during infancy are particularly susceptible to thyroid cancer. The cells of children and adolescents proliferate vigorously, and radiation is an additional stimulus that easily triggers the formation of tumors. The chances of developing thyroid cancer after receiving cervical radiation therapy in adults are rare. 3. Chronic thyroid stimulating hormone and thyroid cancer thyroid follicles are highly differentiated, with iodine and synthetic thyroglobulin function. TSH also regulates the growth of thyroid follicular cells through cAMP-mediated signaling pathway, and thyroid cancer may occur. Serum TSH levels are elevated, nodular goiter is induced, and thyroid follicular carcinoma can be induced by mutagen and TSH stimulation, and clinical studies have shown that TSH inhibition therapy plays a role in the treatment of differentiated thyroid cancer after surgery. An important role, but whether TSH stimulation is a causative factor in the development of thyroid cancer remains to be confirmed. 4. The role of sex hormones and thyroid cancer Because in the well-differentiated thyroid cancer patients, women are significantly more than men, so the relationship between sex hormones and thyroid cancer is valued, clinically compared to the tumor size of well-differentiated thyroid cancer, usually young people The tumor is larger than that of adults. Young people have cervical lymph node metastasis or distant metastasis of thyroid cancer earlier than adults, but the prognosis is better than that of adults. There are also maternal women, but the incidence of women after 10 years of age is significantly increased. It is possible that estrogen Increased secretion is associated with the development of thyroid cancer in young people. Therefore, some people have studied the sex hormone receptors in thyroid cancer tissues and found that there are sex hormone receptors in the thyroid tissue: estrogen receptor (ER) and progesterone receptor (PR), and the thyroid gland. ER in cancer tissues. However, the impact of sex hormones on thyroid cancer is still inconclusive. 5. Animals with thyroid gland and thyroid cancer have confirmed that taking thyroid material for a long time can induce thyroid cancer, which can also hinder the synthesis of thyroid hormone, increase the secretion of TSH, stimulate thyroid follicular hyperplasia, and possibly produce new thyroid gland. The organism, accompanied by diffuse enlargement of the thyroid gland, causes thyroid tumors. 6. Other thyroid diseases and thyroid cancer (1) Nodular goiter: Thyroid cancer occurs in nodular goiter. It has always been a risk factor for thyroid cancer, and thyroid cancer occurs in nodular goiter. The rate can be as high as 4% to 17%, but the relationship between nodular goiter and thyroid cancer has always been controversial, and the relationship between benign nodules and well-differentiated cancer progression is unclear. The reasons for the inevitable connection between thyroid cancer and nodular goiter are: 1 Compare the histological changes of nodular goiter and thyroid cancer. Nodular goiter is a lesion of thyroid follicles. The bubble is highly expanded, the cells of the follicular wall are flat, and the expanded follicles are aggregated into nodules of varying sizes, filled with a large amount of colloid, and the fibrous envelope around the nodules is incomplete. But the most common thyroid cancer is not follicular thyroid cancer but papillary thyroid cancer. 2 comparing the age of onset of nodular goiter and thyroid cancer, found that the age of onset of thyroid cancer is significantly lower than the age of onset of nodular goiter, does not seem to support thyroid cancer secondary to nodular goiter. 3 compare the incidence of nodular goiter and thyroid cancer, nodular goiter in the population of 40,000 / 1 million, and thyroid cancer is only 40 / 1 million, far less than thyroid cancer in the nodular thyroid The incidence of swelling is 4% to 17%; the high incidence of thyroid cancer in nodular goiter is related to the selected cases of surgical treatment. In some cases, malignant thyroid disease is suspected in clinical practice, so it is not universal. significance. Despite this, the presence of thyroid cancer in nodular goiter is still an indisputable fact. Nodular goiter is caused by TSH-induced follicular epithelial hyperplasia in different parts of the thyroid gland, resulting in papillary hyperplasia and angiogenesis, papillary Hyperplasia may occur in papillary thyroid cancer. After feeding rats or mice with drinking water and food in areas with iodine deficiency, serum TSH levels are increased, not only to induce nodular goiter, but also to produce thyroid gland in nodular goiter. Cancer, including papillary thyroid cancer and follicular thyroid cancer, has a prevalence of thyroid cancer of 15.6%, which is a risk factor for thyroid cancer. (2) thyroid hyperplasia: the relationship between thyroid hyperplasia and thyroid cancer is not clear, it has been reported that congenital proliferative goiter has not been properly treated for a long time, and eventually thyroid cancer occurs, so congenital proliferative goiter is found in time, and It is very important to eliminate the long-term stimulation of TSH by thyroid hormone replacement therapy. (3) thyroid adenoma: Most people think that thyroid cancer occurs with single thyroid adenoma. If thyroid cancer is secondary to thyroid adenoma, the type of thyroid cancer should be mainly follicular carcinoma, but the actual thyroid nipple Most of the cancers in the thyroid follicular carcinoma often have a history of adenomas, but it is difficult to confirm the relationship between them. Even with histological observation, it is difficult to confirm the relationship between them. (4) Chronic lymphocytic thyroiditis (Hashimoto thyroiditis, HT): In recent years, more and more reports of thyroid cancer have been found in HT, the incidence rate is 4.3% to 24%, the difference is large, and because HT does not need more Surgical treatment, the actual incidence is more difficult to estimate, HT and thyroid cancer can be two unrelated diseases while coexisting in the gland of the thyroid gland, on the other hand, focal HT may also be the body's thyroid cancer Immune response, HT may lead to destruction of thyroid follicular cells, hypothyroidism, decreased thyroid hormone secretion, feedback caused by increased TSH, TSH continues to stimulate thyroid follicular cells, thyroid follicular cells hyperplasia and cancer; may also be TSH as a contributing factor Carcinogenesis occurs at the same time as thyroid oncogene overexpression; others believe that HT has a common background of autoimmune abnormalities with thyroid cancer. (5) Hyperthyroidism: Because of the low level of serum TSH in patients with hyperthyroidism, it has been previously thought that thyroid cancer does not occur in patients with hyperthyroidism, or the incidence of thyroid cancer is consistent in patients with hyperthyroidism and the general population (0.6% to 1.6%). The incidence of thyroid cancer is 2.5% to 9.6%. In thyroid cancer, the incidence of hyperthyroidism can reach 3.3% to 19%, while patients with hyperthyroidism who are treated surgically are either due to large thyroid gland or because thyroid gland is already present. Section, so the actual incidence is unclear, and most of them are treated with drugs. Therefore, we should pay attention to the clinical situation of hyperthyroidism combined with thyroid cancer, and should be alert to the existence of thyroid cancer. Thyroid cancer can be seen in a variety of causes of hyperthyroidism, including Graves disease, while the secretion of thyroid hormone by the tumor itself causes hyperthyroidism is rare, LATS), LATS is not stimulated by feedback inhibition of thyroid hormone to stimulate thyroid follicles, TSAb is a TSH receptor antibody (TSH Receptor Antibodies, TRAb), may induce thyroid cell malignant transformation, thyroid cancer, but has not been confirmed, but still controversial, whether it is Graves disease, or toxic nodular goiter, tumor lesions are small or For occultity, the incidence of metastasis is low, the prognosis is good, and it is similar to thyroid cancer in patients with non-hyperthyroidism. 7. Family factors and thyroid cancer Thyroid cancer is less common as an independent familial syndrome, but it can be used as part of familial syndrome or hereditary disease. A small number of families have a tendency to have multi-focal differentiated thyroid cancer, thyroid cancer. Familial colonic polyposis (such as Gardner syndrome), including colon adenomatous polyps with soft tissue, with fibromatosis most, with fibrosarcoma, is an autosomal dominant genetic disease, consisting of APC genes located on chromosome 5q21 ~ q22 Due to mutation, the latter is a signaling protein involved in the regulation of cell proliferation, and a few people can develop cancer under TSH stimulation. Thyroid cancer. (II) Pathogenesis 1. Molecular biology Molecular biology research progress indicates that the transformation of human normal cells into malignant tumor cells has accumulated a variety of molecular biological changes, including initiation, resulting in cell growth without normal growth. Regulatory control, or cells do not respond to normal regulation, eventually malignant changes in cells, thyroid cancer has a variety of oncogenes and tumor suppressor gene abnormalities, gene amplification and other pathways activate, transforming normal cells into uncontrolled malignant growth Cells must be involved in other genes. Cell malignant transformation usually has several genes, or gene mutations and amplification occur simultaneously. This section discusses molecular biological changes in thyroid cancer. (1) trk, trk, trk) is located in the q31 region of chromosome 1, encoding a cell surface receptor of a nerve growth factor belonging to a receptor tyrosine kinase, such as a Trk-T1 oncogene conjugated with TPP to activate . The expression of the trk oncogene can be found in papillary thyroid carcinoma. The met(7q31) gene has 120 kb, including 21 exons separated by 20 introns, a transmembrane receptor tyrosine kinase, metephropathy in various cancerous tissues, but thyroid follicular The expression in cancer is only 25%. The original recognition of the ret proto-oncogene is due to its ability to efficiently transform cultured NIH3T3 fibroblasts. It is a dominant transforming oncogene that plays a role in the development of medullary thyroid carcinoma and papillary thyroid carcinoma, including 20 The phenotype, about 30 kb in length, encodes a transmembrane tyrosine kinase receptor, and is expressed by the extracellular ligand binding region, the neural crest cells, and the genitourinary system. The system, which regulates neural crest cell proliferation, MEN) type 2, is activated by gene rearrangement in papillary thyroid carcinoma. In 1987, Fusco found that 25% of thyroid papillary carcinomas and their metastatic lymph nodes have conversion sequences in DNA transfection experiments, which are considered to be new oncogenes and named PTC (representing thyroid papillary carcinoma), resulting in coding The ret gene of the tyrosine kinase is produced by juxtaposition with the 5' end sequence of one of the various unrelated genes, so it is called ret/PTC oncogene. According to the difference of the collocated sequence, at least 7 ret/ have been identified. PTC oncogenes, such as ret proto-oncogenes, D10S170 (H4) gene rearrangement (ret/PTC1) on the same chromosome, ret proto-oncogene and RIα gene rearrangement on chromosome 17 (ret/PTC2), ret primary cancer The rearrangement of the gene and the RFG/ELE1 gene located in the same chromosomal region (ret/PTC3) is the most common mode of activation. It was found that the ELE1 gene and the ret proto-oncogene tyrosine kinase coding region are linked to the 5' end of other genes. The encoded protein exhibits phosphorylation activity and is activated by the formation of a dimer with its physiological ligand GDNF. Ret/PTC gene-encoded dimeric protein-mediated ret kinase activation, ret/PTC oncogene also has a transforming effect on cultured thyroid cells, indicating that ret gene mutation is associated with tumorigenesis initiation, ret/PTC oncogene The expression is almost exclusively in papillary thyroid carcinoma, the incidence rate is 5% to 44%, and the ret/PTC positive expression rate of thyroid papillary carcinoma in children associated with the Chernobyl nuclear accident is as high as 67% to 87%, and Mostly RET/PTC3. Differences in incidence may reflect geography. There is no significant difference in the pathological features of thyroid papillary carcinoma or trk oncogene expressing ret/PTC oncogene. It is possible that trk functions similarly to ret/PTC, but not in ret/PTC and TRK. In typical papillary thyroid carcinoma, it may be that other receptor tyrosine kinases or their downstream signaling molecules cause corresponding nuclear changes, and patients with multiple mucosal neuroma have almost the 918th retinoin gene. Sub-mutation, in the sporadic MTC, the incidence of codon mutation at position 918 of the ret proto-oncogene can reach 33% to 67%, but not in the DNA of normal cells, which may occur just in the receptor tyrosine. The catalytically active site of the acid kinase. A mutation in codon 918 of the ret proto-oncogene may indicate a poor prognosis. (2) ras gene: The name of the ras gene is derived from the prefix of rat sarcoma, which was isolated from the retrovirus of rat sarcoma in 1964 and located in Kirstern of the short arm of chromosome 12 (12p). K)-ras and neuroblastoma(N)-ras located on the short arm of chromosome 1 (1p1), which are composed of 4 exons and 5 introns respectively. The encoded proteins are 21kD protein p21ras. It consists of 188-189 amino acid residues, is immobilized on the inner side of the cell membrane, has GTPase (GTPase) activity, and is a member of the large family of G proteins. Although it is a small molecule, it is different from the G protein with a trimer structure. It has the function of regulating cell growth and differentiation, is an intracellular signal transduction, and transmits growth signals to cells. When p21ras binds to GTP, it is activated. After GTP hydrolysis, p21ras binds to GDP in an inactive state. The ras oncogene passes through the 12th, changes the GTP binding or GTPase activity of the p21 protein, and isolates the H-ras oncogene with dominant activation. The 12th codon of H-ras changes from normal -GGC-(glycine) -GTC-(valine), the mutant H-ras is exactly the same as the oncogene VH-ras in Harveg sarcoma virus. This amino acid change affects the spatial conformation of p21ras, which reduces the GTPase activity by 1000-fold, while the p21ras protein is at The activation state combined with GTP causes cell malignant transformation, so the normal product becomes a carcinogenic product. Mutations in the ras oncogene are found in a variety of human malignancies. The role of ras protein in the signal transduction process of normal thyroid follicular cell proliferation is still unclear. Whether it is a benign thyroid adenoma or a malignant differentiated or undifferentiated carcinoma, there is a point mutation in the ras oncogene, indicating that The ras oncogene mutation occurs in the early stage of thyroid follicular cell tumor formation. The mutant ras interacts with other oncogenes to transform normal adult thyroid follicular cells, stop differentiation, proliferate, reduce iodine, and express thyroid gland. Oxidase, even in human tissue culture, forms cell clones similar to thyroid tumors. Mutations in the ras gene are associated with thyroid follicular carcinoma. The mutation rate of ras gene detected in radiation-related thyroid tumors can reach 60%. (3) myc gene: members of the myc gene family include c-myc, a nuclear transcription factor protooncogene, a protein encoding 439 amino acid residues, the product of which is a protein of 456 amino acid residues, and the encoded product is 364 amino acids. The protein of the residue is a nuclear transcriptional regulator. The myc protein can be structurally divided into a transcriptional activation region, a non-specific DNA binding region, a nuclear target sequence, an alkaline region, a helix-loop-helix and a leucine zipper region, and a base. The sex region follows the spiral-loop-helix and can be combined with special chromosomal DNA sequences to regulate the transcription process, regulate cell growth, and have the chromosomal gene translocation of myc gene in the body tumor, which is regulated by various substances. The regulatable gene is also a gene that allows cells to proliferate indefinitely and promote cell division. The c-myc gene is also involved in apoptosis. Read more...