Molecular Changes

Experimental evidence has allowed the delineation of a few crucial pathways in human primary cell transformation. Although there are many important cellular capabilities, allowing a normal cell to bypass cell cycle arrest checkpoints, escape apoptosis, guard against crisis, and provide its own mitogenic signals, may be sufficient to allow for transformation to the oncogenic phenotype. These basic genetic elements may be generalized to most human cancers, however, specific alterations that...

Future Of Animal Models Investigating Thyroid Carcinogenesis

In the last 75 years, very different models investigating thyroid carcinogensis have been developed. The concept of initiation and promotion of carcinogenesis is well demonstrated by the studies reviewed in this chapter. The initiation step may be produced by diverse agents, including ionizing radiation and many classes of carcinogens. The action of these agents is promoted by raising the level of trophic stimulation (TSH), which can also be achieved in a variety of ways (for instance goitrogen...

References

Abbatt JD, Doniach I, Howard-Flanders P, Logothetopoulos JH Comparison of the inhibition of goitrogenesis in the rat produced by X-rays and radioactive iodine. Br J Radiol 1957 30 86-88. 2. Akimova P, Gonina R, Zotikov LA, Kulik GI Results of a biochemical, histochemical and ultrastructural study of the thyroid gland in the process of experimental carcinogenesis. In Hedinger C (ed) Thyroid cancer. UICC Monograph series, volume 12, Springer-Verlag Berlin, 1969, pp. 149-154. 3. Al-Saadi Precursor...

Preoperative Evaluation Of Thyroid Nodules

Thyroid nodules are extremely common with prevalence rates approaching 50-60 of adults under 60 years old. Because only approximately 5 of thyroid nodules are malignant, accurate pre-operative characterization of thyroid nodules is critical in selecting patients appropriate for surgical thyroidectomy. Fine needle aspiration (FNA) is the single most important diagnostic procedure in the evaluation of thyroid nodules. Table 1. Molecular markers for thyroid nodules and lymph nodes Potential...

Info

For diagnostic purposes the gamma emissions are important. The distribution of the radiopharmaceutical inside the body can be externally measured through imaging with gamma cameras. For therapeutic purposes the beta energy emission is important because of the destructive character in tissue. The path length of the beta particle depends on the energy and ranges from several mm to 1 cm. An important property of is that it can both be used for imaging purposes (high energy gamma ray) as well as...

Spontaneous Thyroid Tumors In Animals

Roe (1965) defined a spontaneous thyroid tumor as a neoplasm that had developed without any influence exerted by internal or external carcinogens. Data on the incidence of spontaneous thyroid tumors in animals are contradictory. McCoy (1909) and Woolley & Wherry (1912) were the first to systematically investigate thyroids of animals. They searched for tumors in 23,000 and 100,000 wild rats, but failed to detect them. In 1917, Bullock and Rhodenburg firstly described nine tumors found in...

Genetic Requirements For Cancer

Epidemiologic analyses have shown that four to six rate-limiting events must occur before a tumor becomes clinically apparent (4,5). The changes that must occur are genetic and or epigenetic in nature. Most of these events result from somatic mutations that occur infrequently or are induced by carcinogen exposure, and only in aggregate do they lead to the tumorigenic state. In a seminal series of studies, Vogelstein and his colleagues described a stepwise genetic history of colorectal tumors...

Staging

The recommended staging system is Musshoff's modification ofthe Ann Arbor staging system (36). See Table 1. Over 90 of patients present as stages IE or IIE. Enlargement of the thyroid gland, either rapidly or slowly, is the commonest gross manifestation (Figure 1). This is often accompanied by extrathyroidal extension into surrounding soft tissue and skeletal muscle. The lymphomatous gland varies in its naked eye appearance fleshy, tan, white, grey or red with a fish-flesh appearance, firm or...

Introduction

The NTRK1 gene encodes the high affinity receptor for Nerve Growth Factor, and its action regulates neural development and differentiation. Deregulation of NTRK1 activity is associated with several human disorders. Loss of function mutations cause the genetic disease Congenital Insensitivity to Pain with Anhidrosis (CIPA). Constitutive activation of NTRK1 has been detected in several tumor types. An autocrine loop involving NTRK1 and NGF is responsible for tumor progression in prostate...

The Retinoblastoma Gene Network

Aberrations of the Rb gene is found in 50 all human tumors (1) and yet it has not been as intensively studied in human cancers as have p53 . Indeed alterations in the Rb signalling pathway, by activation of positive acting components such as G1 cyclins and cyclin-dependent kinases (cdk), by inactivation of negative acting components such as cdk inhibitors and p53, or by mutations in Rb itself has been detected in virtually all human cancers (58). Rb plays a pivotal role in the G1 checkpoint in...

Gene Expression Profiling In Thyroid Cancer

A limited number of studies have reported on DNA microarray studies in thyroid cancer two on follicular tumors, one on papillary carcinoma (PTC) and only one that examined a range of benign and malignant thyroid disease. The numbers of samples analyzed in each study was small to moderate in size. Most of the studies quoted are, however, robust and pass muster for the stringent rules stipulated for reporting of gene expression studies (4). Huang et al. (12) used oligonucleotide DNA chips...

C

Ligand binding RXR interation transattivation Figure 2. PPARy Gene Rearrangements in Follicular Thyroid Carcinoma. The breakpoints of two chromosomal rearrangements, t(2 3)(q13 p25) and t(3 7)(p25 q31), have been cloned from human follicular thyroid carcinomas. Each rearrangement encodes a chimeric fusion protein that contains identical domains (A-E) of the PPARy nuclear receptor. well with the known tumor suppressor-like effects of wild-type PPARy in a variety of epithelial cells 40-44 . In...

Experimental Induction Of Thyroid Tumors

Methods for inducing thyroid tumors in animals can be subdivided into two groups according to the mechanism of action. The first group comprises methods based on the application of substances with a direct oncogenic effect on thyroid cells, i.e., proper carcinogenic agents. The methods in the second group aim primarily at establishing a hormonal imbalance that, in turn, will lead to tumor development. Such a division, however, is rather artificial. Some known carcinogenic agents with a direct...

Radiationassociated Thyroid Tumors

The thyroid gland is highly sensitive to radiation during childhood, the excess relative risk per Gray being 7.7, and 88 of thyroid cancers occurring in these subjects being attributable to radiation. The irradiated thyroid gland is thus an adequate model for the study of radiocarcinogenesis. Several epidemiological studies have suggested a familial predisposition to developing a thyroid carcinoma after irradiation. Firstly, approximately 3-5 of patients with thyroid cancer, without previous...

Relationship Between Low And Highgrade Maltlymphomas

The coexistence of low- and high-grade MALT-lymphoma suggests either a patho-genetic link between the two components, or that they represent two independent de novo clones. The weight of evidence points to a close relationship between the low-and high-grade foci often there is a transition noted microscopically, both immuno-histochemical and molecular studies substantiate commonality and transformation of low-grade to high-grade lymphoma, and the clinical presentation of a sudden and or rapid...

Anaplastic Carcinoma

Anaplastic or undifferentiated carcinoma accounts for 5 to 10 of all primary malignant tumors of the thyroid (192) but in many centres this is decreasing with earlier detection of disease. These tumors are rapidly growing, with massive local invasion that usually overshadows the early metastases, most frequently to lung, adrenals and bone (4,5). They are highly lethal with a 5 year survival rate of 7.1 (193) and a mean survival period of 6.2 to 7.2 months (193,194). Microscopically, anaplastic...

Abnormal Expression Of Estrogen And Progesterone Receptors In Thyroid Cancer

Thyroid carcinoma is more common in women than in men (5). For 2003, the estimate of new cases of thyroid cancer has a female predominance with a 2.9 1 ratio (6). This predominance suggests that estrogens may play a critical role in the development of thyroid carcinoma. In the past two decades, efforts have been made to demonstrate the presence of estrogen receptors (ERs) in thyroid tumors and to correlate tumor malignancy with ER expression. Using a dextran-coated charcoal method and analysis...

Immunohistochemistry

The use of immunohistochemistry in thyroid lymphomas is somewhat limited in that there isn't a characteristic or diagnostic immunoprofile. The application of LCA and cytokeratins as a first line investigation usually accomplishes the separation of lymphoma from carcinoma. MZBL of MALT-type, MZBL with blasts and DLBCL are all B-cell lymphomas and will stain positively with traditional B-cell markers CD20, CD79a . The reactive T-cells decorate with CD3, while light chain restriction in plasma...

Thyroid Follicular Hyperplasia And Neoplasia

Follicular nodules are the most commonly encountered problems in the surgical pathology of the thyroid. These lesions can be classified along the full spectrum of thyroid pathology from hyperplastic nodules to benign follicular adenomas and malignant fol-licular carcinomas. Sporadic nodular goitre is characterised by numerous follicular nodules with heterogeneous architecture and cytology, features that have suggested a hyperplastic rather than neoplastic pathogenesis 7-10 . The gland may be...

Papillary Lesions Of Thyroid

Hyperplastic nodules and adenomas with papillary architecture The papillary hyperplastic nodule of the thyroid is usually identified in girls, usually teenagers in and around the age of menarche. These present as solitary nodules and it is unusual for them to be associated with clinical hyperfunction, although that might occur. These lesion are distinguished from papillary carcinoma in that they are totally encapsulated, often show central cystic change, have subfollicle formation in the...