Prevalences of G<sub>s</sub>α, ras, p53 mutations and ret/PTC rearrangement in differentiated thyroid tumours in a Korean population

Park, K Y; Koh, Jung‐Min; Kim, Y I; Park, H J; Gong, Gyungyub; Hong, Suck Joon; Ahn, Il-Min

doi:10.1046/j.1365-2265.1998.00515.x

Cited by 59 publications

(60 citation statements)

References 31 publications

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“…Meta-analysis of the data published worldwide over a greater than 10-year period (Table 3) demonstrates an average prevalence of 18% for Southern blotting (67/370 cases tested, range 0-33%), [26][27][28][29][30][31] 15% for direct visualization of the RT-PCR amplicons (47/309 cases tested, range 4-45%) 7,32-35 and 48% for hybridization of blotted RT-PCR products (153/314 cases tested, range 0-85%). 4,[21][22][23][36][37][38][39] Allowing for the fact that Southern blotting permits the identification of all RET/PTC variants while the cases analyzed by RT-PCR listed above only screened the tumors for RET/PTC1, -2 and -3, there is a good correspondence between the sensitivity of Southern blotting and of direct gel visualization of RT-PCR products, as also demonstrated by parallel analysis of the same samples with the two methods. 44 When RT-PCR is followed by blotting of the amplicons and hybridization with RET-specific probes the sensitivity increases dramatically, by at least 100-fold according to some investigators.…”

Section: Discussionmentioning

confidence: 99%

Real-time quantitative RT-PCR identifies distinct c-RET, RET/PTC1 and RET/PTC3 expression patterns in papillary thyroid carcinoma

Rhoden

Johnson

Brandao

et al. 2004

Laboratory Investigation

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RET/PTC1 and RET/PTC3 are the markers for papillary thyroid carcinoma. Their reported prevalence varies broadly. Nonrearranged c-RET has also been detected in a variable proportion of papillary carcinomas. The published data suggest that a wide range in expression levels may contribute to the different frequency of c-RET and, particularly, of RET/PTC detection. However, quantitative expression analysis has never been systematically carried out. We have analyzed by real-time RT-PCR 25 papillary carcinoma and 12 normal thyroid samples for RET/PTC1, RET/PTC3 and for RET exons 10-11 and 12-13, which are adjacent to the rearrangement site. The variability in mRNA levels was marked and four carcinoma groups were identified: one lacking RET/ PTC rearrangement with balanced RET exon levels similar to those of the normal samples (7/25 cases, 28%), the second (6/25 cases, 24%) with balanced RET expression and very low levels of RET/PTC1, the third with unbalanced RET exons 10-11 and 12-13 expression, high RET/PTC1 levels but no RET/PTC3 (7/25 cases, 28%), and the fourth with unbalanced RET expression, high RET/PTC1 levels and low levels of RET/PTC3 (5/25 cases, 20%). Papillary carcinomas with high RET/PTC1 expression showed an association trend for large tumor size (P ¼ 0.063). Our results indicate that the variability in c-RET and RET/PTC mRNA levels contributes to the apparent inconsistencies in their reported detection rates and should be taken into account not only for diagnostic purposes but also to better understand the role of c-RET activation in thyroid tumorigenesis. Oncogenic c-RET activation in thyroid tumors composed of follicular cells is the result of chromosomal rearrangements resulting in the fusion of the RET tyrosine-kinase (RET-TK) domain to the 5 0 -terminal region of heterologous genes. The rearrangements are a molecular marker for papillary thyroid carcinoma as their very name, RET/PTC for papillary thyroid carcinoma, implies, 1 and consist of balanced inversions or translocations that involve the 3.0 kb intron 11 of c-RET. To date, at least 16 chimeric mRNAs affecting 11 different genes have been reported (Saenko et al, 2 reviewed in Tallini and Asa 3 ), of which RET/PTC1 (consisting of the fusion of RET with H4) and RET/PTC3 (consisting of the fusion of RET with RFG/ELE1) are by far the most common. 3 Their prevalence varies broadly from zero to more than 60% in nonradiation-associated cases 3 and is close to 90% in some series of papillary carcinomas from the Chernobyl area diagnosed after the 1986 nuclear disaster. 4 While the high prevalence of RET/PTC in radiation-associated thyroid tumors is consistent with misrepair of radiationinduced double-strand DNA breaks, 5,6 the high variability in the prevalence of RET/PTC in sporadic tumors has no specific explanation. In addition to rearranged RET forms, c-RET expression has also been identified in a highly variable proportion of papillary carcinoma samples. Although its signifi-

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Section: Discussionmentioning

confidence: 99%

Real-time quantitative RT-PCR identifies distinct c-RET, RET/PTC1 and RET/PTC3 expression patterns in papillary thyroid carcinoma

Rhoden

Johnson

Brandao

et al. 2004

Laboratory Investigation

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“…Certain studies regarding the immunohistochemical analysis of p53 expression have demonstrated that p53 overexpression may act as a significant and independent prognostic indicator for differentiated thyroid carcinomas (3,4,7,22,24). However, this association has provided controversial results (3,5,21,30,31).…”

Section: Discussionmentioning

confidence: 99%

“…In thyroid cancers, it was suggested that the presence of p53, as detected by immunohistochemistry, was associated with the occurrence of p53 gene mutations (5); however, the detection of p53 protein expression was also reported in differentiated papillary and follicular thyroid carcinomas regardless of the occurrence of p53 gene mutations; of note, the incidence rate of p53 protein overexpression in PTC was reported to be between 11 and 59% (4,(21)(22)(23)(24)(25).…”

Section: Discussionmentioning

confidence: 99%

“…p53 protein overexpression, as determine by immunohistochemistry, was reported to be correlated with the presence of p53 gene mutations (7); however, the immunohistochemical detection of p53 overexpression has been identified in differentiated follicular and papillary thyroid carcinomas regardless of the occurrence of p53 gene mutations. p53 protein overexpression was reported to have an incidence rate of between 11 and 59% (6,22,23). Certain studies regarding the immunohistochemical analysis of p53 protein expression have demonstrated that p53 overexpression may be used as an independent prognostic indicator for differentiated thyroid carcinomas (3)(4)(5)(6)(7)22,24).…”

Section: Introductionmentioning

confidence: 99%

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Associations of the BRAF (V600E) mutation and p53 protein expression with clinicopathological features of papillary thyroid carcinomas patients

et al. 2015

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Abstract. The BRAF (V600E) mutation is the most prevalent type of genetic alteration that has been identified in papillary thyroid carcinoma (PTC); in addition, previous immunohistochemical studies have revealed the overexpression of p53 protein in PTC. The aim of the present study was to investigate the prevalence of the BRAF (V600E) mutation and the expression of p53 in PTC, as well as to determine any associations between these two factors and the clinicopathological features of PTC. The study was performed on 66 PTC patients who underwent surgical tumor resection between January and December 2012. Polymerase chain reaction-based DNA amplification was used to analyze extracted DNA from the tumor specimens in order to determine the prevalence of the BRAF (V600E) mutation. In addition, immunohistochemical analysis was employed in order to evaluate the protein expression of p53 in sections of tumor tissue. Furthermore, statistical analysis was performed in order to determine any associations among the BRAF (V600E) mutation prevalence, p53 overexpression and the clinicopathological features of PTC patients, including age, gender, tumor size, multiplicity, lymph node metastasis and extrathyroidal extension. The results revealed that the BRAF (V600E) mutation was observed in 50 (75.8%) of the 66 PTC patients and overexpression of p53 was found in 52 (78.8%) of 66 cases. No significant correlations were observed between the BRAF (V600E) mutation or p53 protein overexpression and the clinicopathological features of patients. However, the BRAF (V600E) mutation demonstrated noteworthy, but non-significant, correlations with the overexpression of p53 (P=0.0854) and extrathyroidal extension (P= 0.0661). In addition, a significant correlation was observed between lymph node metastasis and bilaterality (P=0.0280). In conclusion, the present study demonstrated that the BRAF (V600E) mutation and overexpression of p53 were not significantly correlated with clinicopathological features of PTC, although notable associations were identified between BRAF (V600E) mutation and overexpression of p53 as well as extrathyroidal extension. In addition, lymph node metastasis was significantly associated with bilaterality.

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“…In thyroid carcinomas, TP53 mutations are not different from those of cancers at other sites and have been described in exons 5-9, with 273 being the codon most often altered (42,67,69,70,71,72,73). No p53 expression or mutation has been found in normal thyroid or in benign lesions, including follicular adenoma, adenomatous goitre and chronic thyroiditis (72,73,74,75,76). For years it was repeated that more than 98% of DTC (PTC and FTC) had a normal TP53 gene (18,69,70,71,72,73,75,77), even when cases secondary to radiation exposure were included (78).…”

Section: Tp53 Mutationsmentioning

confidence: 99%

ENDOCRINE TUMOURS: Genetic predictors of thyroid cancer outcome

Tavares

Melo

Cameselle-Teijeiro³

et al. 2016

European Journal of Endocrinology

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Genetic predictors of outcome are reviewed in the context of a disease -cancer -that can be (too) simplistically described as a 'successful, invasive clone of our own tissues'. Context has many faces that determine a thyroid cancer patient's outcome beyond the influence of genetic markers. There is also plenty of evidence on the prognostic meaning of the interplay between genetics and context/microenvironment factors (encapsulation, degree of invasion, staging, etc.). This review addresses only genetic alterations detected by molecular methods in surgically resected specimens, thus ruling out immunohistochemistry and (F)ISH, despite their crucial relevance as topographically oriented methods. For the sake of the discussion, well-differentiated carcinomas were divided into two main morphologic types: papillary carcinoma (classic and most variants) displaying BRAFV600E mutations and RET/papillary thyroid carcinoma rearrangements and the group of follicular patterned carcinomas that encompasses follicular carcinoma and the encapsulated form of follicular variant of papillary carcinoma, displaying RAS mutations and PAX8/PPARg rearrangement. TERT promoter mutations have been recently described (and associated with distant metastases and reduced survival) in papillary and follicular carcinomas, as well as in poorly differentiated and undifferentiated carcinoma. TP53 mutations, previously thought to be restricted to less differentiated carcinomas, were also detected in papillary and follicular carcinoma and found to carry a guarded prognosis. Besides their putative importance for targeted therapies, the prognostic meaning of such mutations is discussed per se and in the setting of concurrent BRAF mutation.

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Prevalences of G_sα, ras, p53 mutations and ret/PTC rearrangement in differentiated thyroid tumours in a Korean population

Cited by 59 publications

References 31 publications

Real-time quantitative RT-PCR identifies distinct c-RET, RET/PTC1 and RET/PTC3 expression patterns in papillary thyroid carcinoma

Real-time quantitative RT-PCR identifies distinct c-RET, RET/PTC1 and RET/PTC3 expression patterns in papillary thyroid carcinoma

Associations of the BRAF (V600E) mutation and p53 protein expression with clinicopathological features of papillary thyroid carcinomas patients

ENDOCRINE TUMOURS: Genetic predictors of thyroid cancer outcome

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Prevalences of Gsα, ras, p53 mutations and ret/PTC rearrangement in differentiated thyroid tumours in a Korean population

Cited by 59 publications

References 31 publications

Real-time quantitative RT-PCR identifies distinct c-RET, RET/PTC1 and RET/PTC3 expression patterns in papillary thyroid carcinoma

Real-time quantitative RT-PCR identifies distinct c-RET, RET/PTC1 and RET/PTC3 expression patterns in papillary thyroid carcinoma

Associations of the BRAF (V600E) mutation and p53 protein expression with clinicopathological features of papillary thyroid carcinomas patients

ENDOCRINE TUMOURS: Genetic predictors of thyroid cancer outcome

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Product

Resources

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Prevalences of G_sα, ras, p53 mutations and ret/PTC rearrangement in differentiated thyroid tumours in a Korean population