Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutational changes in the p53 tumor suppressor gene are the most frequent genetic alterations in human malignant tumors. Studies have shown a correlation of p53 expression in breast cancer with tumor prognosis. In contrast to mutational activation of ras and GSP in thyroid tumors, little is known about the role of p53 in thyroid tumor development. Therefore thyroid tumors and thyroid tumor cell lines were studied for the presence of p53 mutations. Snap-frozen tissues from 57 differentiated thyroid carcinomas (DTCs) and 5 goiters were studied by immunohistochemical methods. A panel of six antibodies (pAb 240, 421, 1620, 1801, DO7, and CM1) was employed by using the ABC technique. Five cell lines from DTCs (FTC133, 236, 238, PTC337, MTC164) were examined by the same technique. Additionally, genomic DNA from the cells was amplified by the polymerase chain reaction (PCR) and the PCR product studied for p53 mutations (R273H) by mutation-specific oligonucleotide hybridization (MOH) and temperature gradient gel electrophoresis (TGGE) for the p53 exon 8. None of the benign thyroid tumors and 7 of 57 (12%) DTCs strongly express p53 with a heterogeneous distribution in the tumor tissue. All seven patients have metastatic disease or dedifferentiated tumors G3 (three of seven). CM1 was positive in two cell lines (FTC-133, PTC-337), questionable in FTC-238, and negative in FTC-236 and MTC-164. All three follicular cell lines, however, and the original tumor tissue showed the same p53 mutation (R273H) in MOH analysis and TGGE. P53 mutations are rare in thyroid tumors, but the presence of p53 mutations indicates a poor prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Significance of P53 in human thyroid tumors. 772 41

Mantle cell (centrocytic) non-Hodgkin's lymphoma (MCL) is a malignant tumour with unique biological features. The pathogenesis of MCL seems to be strongly associated with aberrant function of the cell cycle. 110 cases of MCL have been analysed for their cytomorphological features, mitotic and proliferation indices, bcl-1 rearrangements, p53 expression patterns and DNA content by both interphase cytogenetic as well as DNA flow cytometric analyses. According to cytomorphology, three subtypes were recognized: a common, a lymphoblastoid and a pleomorphic variant of MCL. Blastic MCL subtypes were characterized by distinctly elevated mitotic and proliferation indices, frequent bcl-1 rearrangements at the MTC locus, and overexpression of p53. The most interesting finding, however, was a striking tendency of blastoid MCL subtypes to harbour chromosome numbers in the tetraploid range, a feature clearly separating these neoplasms from other types of B-cell NHL and possibly being related to its unphysiological expression of cyclin D1. Although characterised by a uniform immunophenotype and common biological background, MCL shows a broad spectrum of morphological features ranging from small cell to blastic types, and this spectrum is mirrored by distinct biological features.
 ...
PMID:The cytomorphological spectrum of mantle cell lymphoma is reflected by distinct biological features. 1003 1

The study of thyroid tumor genetics has great relevance to surgeons and facilitates understanding tumor pathogenesis, prediction of tumor behavior, and management decisions. The genes implicated can be broadly categorized as oncogenes or tumor-suppressor genes. The RET oncogene has well established roles in the development of both papillary (PTC) and medullary (MTC) thyroid carcinoma. Genetic screening for germline RET mutations in members of multiple endocrine neoplasia type II (MEN-II) families is now widely performed, and prophylactic thyroidectomy in gene carriers is advisable at an early age. Patients with apparently sporadic MTC can also be screened to rule out familial disease. The demonstration of a RET rearrangement in a patient's PTC may have prognostic significance, but as yet there are no management implications. The thyrotropin receptor (TSH-R) and Gsalpha become oncogenic through point mutation and are associated with the development of toxic thyroid adenomas. The ras oncogene is implicated in the early stages of development of several thyroid tumor types. Tumor-suppressor genes also have a role in thyroid tumor formation. The p53 gene appears to be involved in the process of transformation to the anaplastic phenotype and the PTEN gene in the development of follicular adenomas but not carcinomas. There is still limited evidence for the so called adenoma-carcinoma sequence of the thyroid follicular cell. Loss of heterozygosity studies have enabled identification of tumor-suppressor genes, and their findings suggests differences in the pathogenesis of PTCs compared with follicular cancers. Surgical decision-making will benefit from these basic molecular advances, which rapidly translates into improved patient management.
 ...
PMID:Molecular genetics of thyroid tumors and surgical decision-making. 1086 36

Analysis of 22 human thyroid cancers including papillary, follicular and medullary subtypes (PTC, FTC, MTC) by PCR-SSCP, and immunohistochemistry detected 4 deletions and 3 mutations. Deletions involved exons 1, 2-3 and 5-6 in 3 PTCs, mutations exons 2-3 in 2 MTCs and exons 8-9 in PTC4. p53 alterations occurred in 2/5 recurrent tumors and 2/3 tumors developing to cell lines. Immuno-histochemistry detected p53 mutations in differentiated areas of papillary thyroid cancers as frequent events occurring at stage T1 to T4 in contrast to prior findings by other authors which restrict p53 alterations to undifferentiated stages.
 ...
PMID:P53 gene alterations in differentiated thyroid cancers. 2159 8