Immunohistochemical localization of p53 in human thyroid neoplasms: Correlation with biological behavior (original) (raw)
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Histopathology, 1994
In an attempt to find whether or not p53 immunoreactivity in the thyroid gland is restricted to undifferentiated carcinomas and to evaluate the putative prognostic usefulness of its detection, we investigated p53 immunoreactivity in a series of 14 benign thyroid lesions and 65 thyroid carcinomas (12 papillary; six minimally invasive follicular; four widely invasive follicular; 31 poorly differentiated and 12 undifferentiated tumours). Unequivocal nuclear immunostaining for p53 was observed in two widely invasive follicular carcinoma (20.0%), five poorly differentiated carcinomas (16.1%) and in 10 undifferentiated carcinomas (83.3%). The percentage of immunoreactive cells was much smaller in the former groups than in undifferentiated carcinomas. Despite a trend to a more aggressive behaviour of the p53 immunoreactive cases no significant differences in the outcome of patients with positive and negative tumours was found when the comparison was made within each category of carcinomas. We conclude that p53 immunoreactivity can be detected both in undifferentiated carcinomas and in some differentiated and poorly differentiated thyroid carcinomas. Larger series of cases are necessary to evaluate the prognostic usefulness of this finding.
p53 in a Thyroid Follicular Carcinoma with Foci of Poorly Differentiated and Anaplastic Carcinoma
Pathology - Research and Practice, 1996
The clinical and pathologic features of a rare case of follicular carcinoma with small foci of poorly differentiated and anaplastic carcinoma are presented. Eight years after the removal of the primary neoplasm, the patient developed pulmonary and brain metastases that were predominantly composed of the poorly differentiated and anaplastic components. A comparative immunohistochemical and molecular analysis of p53 status in the follicular, poorly differentiated and anaplastic components of the tumor was performed. p53 immunostaining was restricted to the poorly differentiated and anaplastic areas. Single strand conformation polymorphism analysis (SSCP-PCR) from DNA obtained by microdissection demonstrated the presence of a mutation (TAT-+ TGT; Tyr-+ Cys) in codon 220, exon six of the p53 gene in the anaplastic component, that was absent in the well-differentiated follicular areas. The results of that study in this rare tumor support that p53 has a tumor progression role in thyroid tumorigenesis.
Significance of P53 in human thyroid tumors
World Journal of Surgery, 1994
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. TGGE seems to be a sensitive method for detecting p53 mutations (1% sensitivity) and might play a role in tumor screening in the future.
Journal of Clinical Investigation, 1993
The p53 gene was analyzed in tumor specimens obtained from 52 patients with various types of carcinoma of the thyroid gland by a combined molecular and immunocytochemical approach. The histologic types included 37 well-differentiated papillary and follicular carcinomas, 8 poorly differentiated, and 7 undifferentiated carcinomas. The p53 gene was shown to be unaffected in all differentiated tumors by single-strand conformation polymorphism analysis. However, in two out of eight (25%) of poorly differentiated carcinomas and five out of seven (71%) undifferentiated carcinomas, p53 mutations were identified and subsequently characterized by DNA sequencing. One undifferentiated carcinoma displayed two areas with varying degrees of differentiation. The comparative analysis of the p53 gene, in both the more and the less differentiated area of this tumor, clearly showed that the p53 mutation was confined to the latter component of the tumor specimen. These results indicate that mutations of the p53 gene are associated with the most aggressive histologic types of thyroid tumors, such as the undifferentiated carcinoma and, to a certain extent, the poorly differentiated carcinoma, and that the alterations of this gene represent a late genetic event in human thyroid carcinogenesis. (J. Clin. Invest. 1993.91:1753-1760 Key words: immunocytochemistry * polymerase chain reaction * single-strand conformation polymorphismtumor progressiontumor suppressor gene Address reprint requests to Dr.
p53 expression in anaplastic carcinomas arising from thyroid papillary carcinomas
Journal of Clinical Pathology, 1994
AIM--To study the expression of p53 tumour suppressor gene in anaplastic carcinomas arising from thyroid papillary carcinomas. METHODS--Formalin fixed, paraffin wax embedded tissues from four cases of anaplastic carcinomas associated with thyroid papillary carcinomas were studied by immunohistochemistry with two different p53 monoclonal antibodies. RESULTS--The anaplastic component showed nuclear immunostaining in two cases, but not in the other two. In
P53 and Expression of Immunological Markers May Identify Early Stage Thyroid Tumors
Clinical and Developmental Immunology, 2013
Background. Besides its major role in cell proliferation, DNA repair, and apoptosis, functional p53 protein is involved in the induction of antitumor cytotoxic-T-cell activity against carcinoma cells. We aimed to investigate p53 and immune cell markers utility as diagnostic and prognostic markers of differentiated thyroid cancer (DTC). Methods. ACIS-III system was used to evaluate p53 and immune cell markers including tumor-associated macrophages (TAM); CD68 and tumor-infiltrating lymphocytes (TIL) subsets such as CD3, CD4, CD8, and CD20 in 206 thyroid carcinomas, 105 benign nodules, and 18 normal tissues. Also, TP53 was sequenced in 78 out of 164 patients with papillary thyroid carcinoma. Results. P53 expression was observed more frequently in malignant than in benign lesions ( < 0.0001) and helped discriminate follicular patterned lesions. In addition, p53 was more frequent in smaller ( = 0.0015), unique tumors ( = 0.0286), with thyroiditis ( = 0.0486) and without metastasis at diagnosis ( = 0.0201). TAM was more frequent in P53 negative tumors ( = 0.002). Infiltration of CD8+ TIL was found in 61.7% of P53 positive and 25.6% of P53 negative DTC ( < 0.001). Conclusions. We suggest that p53 and CD8+ TIL immune profile analysis might be useful in DTC.
Clinical Significance of P53 Protein Expression in Papillary Thyroid Carcinoma
World Journal of Surgery, 2008
Background Although mutations in the p53 suppressor gene in thyroid carcinoma have usually been detected in anaplastic carcinoma, P53 protein expression has been detected immunohistochemically in papillary thyroid carcinoma (PTC). In the present study, we examined the immunohistochemical expression of P53 protein in PTC to investigate the relations between its expression and the clinicopathologic features. Methods The study was performed on 68 patients in whom thyroidectomy with lymph node dissection had been performed to treat PTC at Teikyo University Hospital. Expression of P53 protein was evaluated immunohistochemically in sections of paraffin-embedded tissue in 68 primary tumors and 196 lymph node metastases. Results Overexpression of P53 protein in the primary tumor was observed in 29 cases (43%). Statistical analysis revealed significant correlation between P53 protein expression in the primary tumor and large tumor size (unpaired t-test: p \ 0.01), the presence of lymph node metastasis (unpaired t-test: p \ 0.05), and the mean number of lymph node metastases (unpaired t-test: p \ 0.05). Although 29 (43%) of the primary tumors overexpressed P53 protein, 143 (73%) of the metastatic lymph nodes overexpressed P53 protein irrespective of whether there was P53 overexpression by the primary tumor.
P53 is an independent prognostic factor for survival in thyroid cancer
Anticancer research
p53 has been reported to be of prognostic importance in different types of cancer. Immunohistochemical measurement of p53 antigen activity could be a prognostic marker for aggressiveness and survival in thyroid cancer. Different types of antibodies have been used to detect p53 in previous studies without direct comparison to each other. A series of 54 patients with thyroid cancer who had undergone thyroidectomy between 1993 and 1998 is reported. All samples were chosen retrospectively and classified by routine histopathology, followed by immunohistopathological examination with three different types of antibodies (PAb1801, CM1 and DO-7) with the peroxidase method. Survival data was generated. The mean time of follow-up was 9.0 years. Eighteen patients died. Twenty-three (42.6%) samples were positive for p53 using the antibody PAb1801, 17 (31.5%) with using CM1 and only 4 (7.4%) cases with DO-7. Statistical analysis determined that the size (p = 0.02) and classification of the tumor ...