PubMed · 14183658
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H A WILMET, R PAULY, M COOLS. 1964-07-15. [PRIMARY HYPERPARATHYROIDISM].. https://pubmed.ncbi.nlm.nih.gov/14183658/
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The high mobility group As (HMGAs) belong to a family of nonhistone nuclear proteins that orchestrate the assembly of nucleoprotein complexes. Through a complex network of protein-DNA and protein-protein interaction, they play important roles in gene transcription, recombination, and chromatin structure. This protein family is involved, through different mechanisms, in both benign and malignant neoplasias. We have recently reported that transgenic mice carrying the Hmga1 or Hmga2 genes under transcriptional control of the cytomegalovirus promoter develop pituitary adenomas secreting prolactin and growth hormone. We have shown that the mechanism of the HMGA2-induced pituitary adenoma is based on the increased E2F1 activity. The expression profile of mouse normal pituitary glands and adenomas induced in HMGA transgenic mice revealed an increased expression of the ccnb2 gene, coding for the cyclin B2 protein, in the neoplastic tissues compared with the normal pituitary gland. Here, we show, by electrophoretic mobility shift assay and chromatin immunoprecipitation, a direct binding of HMGA proteins to the promoter of ccnb2 gene, whereas luciferase assays showed that HMGAs are able to up-regulate ccnb2 promoter activity. Finally, we report an increased CCNB2 expression in human pituitary adenomas of different histotypes that is directly correlated with HMGA1 and HMGA2 expression. Because cyclin B2 is involved in the regulation of the cell cycle, these results taken together indicate that HMGA-induced cyclin B2 overexpression gives an important contribution to experimental and human pituitary tumorigenesis.
PURPOSE: Since the concept of "advanced" or "dangerous" adenomas was introduced in 1992, less concern has been directed to diminutive colorectal adenomas. They apparently confer no increased risk of metachronous colorectal cancer and some investigators have suggested that they need neither follow-up nor treatment. This study is intended to discover how often small colorectal adenomas have unfavorable histologic features. METHODS: Since 1995 the details of all colorectal polyps have been entered into a database, along with data concerning patients, symptoms, treatment, and outcome. Using this database all adenomas were categorized into three groups: Group I, <6 mm diameter, Group II, 6 to 10 mm diameter, and Group III, >10 mm diameter. "High risk" adenomas were defined as those containing >25 percent villous architecture, those with severe dysplasia, and those over 10 mm in size. Thus all Group III adenomas are high-risk by definition. The effects of family history, patient age, and polyp location on the proportions of Group I and Group II adenomas that were histologically high risk were examined. RESULTS: There were 5,722 polyps of which 4,381 (76.6 percent) were Group I, 666 (11.6 percent) were Group II, and 675 (11.8 percent) were Group III. These included 24 invasive cancers (2 in Group I, 1 in Group II, and 21 in Group III. Of the Group I adenomas, 91/2,064 (4.4 percent) were high risk compared to 65/417 (15.6 percent) in Group II. Of the 564 Group III adenomas, 326 (57.8 percent) had unfavorable histology. There was no effect of age, family history, or site of the polyp on the proportion of polyps that were high risk. CONCLUSIONS: Four percent of adenomas less than 6 mm diameter and 16 percent of those between 6 and 10 mm have unfavorable histology. Small adenomas can still be clinically significant and should not be ignored. Since the concept of "advanced" or "dangerous" adenomas was introduced in 1992, less concern has been directed to diminutive colorectal adenomas. They apparently confer no increased risk of metachronous colorectal cancer and some investigators have suggested that they need neither follow-up nor treatment. This study is intended to discover how often small colorectal adenomas have unfavorable histologic features.
Thyroid nodules are common clinically (prevalence, about 5%) and even more common on ultrasound examination (about 25%). About 5% of thyroid nodules are malignant. Most thyroid cancers are well-differentiated papillary or follicular tumours with an excellent prognosis (10-year survival, 80%-95%). The incidence of papillary thyroid cancer appears to be increasing on the east coast of Australia. Fine-needle aspiration biopsy of the thyroid is the most cost-effective diagnostic tool. Recommended initial management of all follicular carcinomas and of papillary carcinomas > 1.0 cm is total thyroidectomy followed by radioiodine ablation. Most patients should be managed postoperatively with doses of thyroid hormone sufficient to suppress plasma levels of thyroid-stimulating hormone. Recurrences can occur many years after initial therapy, and follow-up should be lifelong. Thyroid nodules are very common, but have a relatively low risk of malignancy