Cytogenetic findings in 31 papillary thyroid carcinomas

Roque, Lúcia; Clode, A.; Gomes, Paula; Rosa-Santos, Jorge; Soares, Jorge; Castedo, Sérgio

doi:10.1002/gcc.2870130304

Cited by 27 publications

(19 citation statements)

References 29 publications

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“…Within the group of benign lesions, aneuploidy is more frequent in adenomas than in nodular goiters [2,11,18,22,30,33]. In the group of malignant tumors, aneuploidy is more frequent in follicular carcinomas than in papillary carcinomas [17,21,22,31].…”

Section: Discussionmentioning

confidence: 99%

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Fetal adenomas and minimally invasive follicular carcinomas of the thyroid frequently display a triploid or near triploid DNA pattern

et al. 2001

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The ploidy pattern and the percentage of S-phase cells were investigated by means of flow cytometry using fresh or frozen samples in a series of 143 tumors and tumor-like lesions of the thyroid in an attempt to find whether there is any relationship between the histological characteristics of the lesions and their DNA content. The percentages of aneuploidy cases per category were: nodular goiter, 18.5% (15/81); fetal adenoma (including cases with trabecular/solid growth pattern), 58.3% (14/24); follicular adenoma other than fetal adenoma, 0% (0/18); papillary carcinoma, 11.1% (1/9); and minimally invasive follicular carcinoma, 57.1% (4/7). Regardless of the histological category, aneuploid lesions had a significantly higher (P < 0.001) percentage of S-phase cells (7.3%) than diploid lesions (4.1%). All the six cases with a DNA content within the triploid range were fetal adenomas, but one was a follicular carcinoma displaying a fetal adenoma-like growth pattern. The other three follicular carcinomas with an aneuploid DNA pattern also displayed foci of fetal adenoma-like growth pattern. Image cytometry of the four aneuploid follicular carcinomas showed similar DNA indexes in the peripheral, invasive foci of the lesions and in the central fetal adenoma-like areas. These results demonstrate that aneuploidy in benign tumors is restricted to adenomas displaying a fetal or fetal/embryonal growth pattern and support the concept that chromosome instability is a major pathway of tumorigenesis in thyroid follicular neoplasms.

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Section: Discussionmentioning

confidence: 99%

“…In the benign lesions of the thyroid, the percentage of cases with abnormal DNA content varies from 10% to 22% in goiters [13,18,31,37] and from 18% to 52% in follicular adenomas [8,18,22,34]. The prevalence of abnormal DNA content is particularly high in Hürthle cell adenomas [6,7,40].…”

Section: Introductionmentioning

confidence: 99%

Fetal adenomas and minimally invasive follicular carcinomas of the thyroid frequently display a triploid or near triploid DNA pattern

et al. 2001

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“…They have a greater tendency to local recurrences and are associated with a higher mortality (20 to 25%) than the classic PTC variant. 4 -6 Furthermore, DNA topoisomerase II 7 and p53 8 expression is higher, p27KIP1 expression lower, 9 and the frequency of trisomy of chromosome 2 higher 10 in the TCV than in classic PTC. Somatic rearrangements of the RET proto-oncogene are the most frequent genetic lesion found in PTC (from 2.5% to 40% depending on the series).…”

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Potent Mitogenicity of the RET/PTC3 Oncogene Correlates with Its Prevalence in Tall-Cell Variant of Papillary Thyroid Carcinoma

Basolo

Giannini

Monaco

et al. 2002

The American Journal of Pathology

103

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The tall-cell variant (TCV) of papillary thyroid carcinoma (PTC), characterized by tall cells bearing an oxyphilic cytoplasm, is more clinically aggressive than conventional PTC. RET tyrosine kinase rearrangements, which represent the most frequent genetic alteration in PTC, lead to the recombination of RET with heterologous genes to generate chimeric RET/PTC oncogenes. RET/PTC1 and RET/PTC3 are the most prevalent variants. We have found RET rearrangements in 35.8% of TCV (14 of 39 cases). Whereas the prevalences of RET/PTC1 and RET/PTC3 were almost equal in classic and follicular PTC, all of the TCV-positive cases expressed the RET/PTC3 rearrangement. These findings prompted us to compare RET/PTC3 and RET/PTC1 in an in vitro thyroid model system. We have expressed the two oncogenes in PC Cl 3 rat thyroid epithelial cells and found that RET/ PTC3 is endowed with a strikingly more potent mitogenic effect than RET/PTC1. Mechanistically, this difference correlated with an increased signaling activity of RET/PTC3. In conclusion, we postulate that the correlation between the RET/PTC rearrangement type and the aggressiveness of human PTC is related to the efficiency with which the oncogene subtype delivers mitogenic signals to thyroid cells. Follicular-cell-derived thyroid tumors are divided into four main types: benign adenomas, well differentiated (papillary or follicular), poorly differentiated, and undifferentiated (anaplastic) carcinomas. Papillary thyroid carcinoma (PTC) is the most common thyroid carcinoma. It is defined on the basis of the architectural pattern and/or distinctive nuclear features, ie, ground glass appearance and longitudinal grooves with cytoplasm invaginations.

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“…The proto-oncogenes ras, ret and trk have been implicated to varying degrees as genetic events involved in the progression of PTC (Fagin, 1994;Bongarzone et al, 1989;Lemoine et al, 1989;Namba et al, 1990;Suarez et al, 1990). Cytogenetic analysis has revealed both trisomy 2 and trisomy 7 (Roque et al, 1995) as well as chromosome 10 alterations consistent with ret and trk activation (Sozzi et al, 1992). Areas of allelic loss that may signify putative tumor-suppressor gene loci have been identified at llq13 in follicular thyroid carcinomas, but a similar alteration has not been described in papillary carcinomas (Matsuo eta!., 1991).p53 mutations have been described in anaplastic or dedifferentiated thyroid cancers but have been very rarely observed in a papillary phenotype (Wright et al, 1991;Ito et al, 1992).…”

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An allelotype of papillary thyroid cancer

et al. 1996

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Although papillary carcinoma accounts for approximately 70% of all thyroid cancers, preliminary studies of allelic loss have thus far not identified any areas of chomosomal deletion. We evaluated 30 papillary thyroid carcinomas for chromosomal loss/allelic imbalance by testing at least 2 microsatellite markers from every autosomal arm. Fifteen of the 30 tumors tested exhibited loss of heterozygosity/allelic imbalance (LOH/AI) at one or more loci. Chromosomal arms with frequent LOH/AI included 4q, Sp, 7p and I I p. An average of I. I chromosomal arms displayed LOH/AI in each individual tumor. Therefore, 4q, 5p, 7p and, to a lesser extent, I I p display significant LOH/AI in papillary thyroid cancer, which indicates the presence of putative tumor-suppressor gene loci at these chromosomal arms.o I996 Witey-Liss, Inc.Papillary thyroid carcinoma (PTC) accounts for approximately 70% of all thyroid cancers (Goepfert and Callender, 1994). This neoplasm exhibits a wide variation in clinical behavior and may result in substantial morbidity and mortality (Robbins et al., 1991). However, little is known about the molecular genetic events involved in the progression of PTC. , 1994). There have been few comprehensive attempts to define other possible areas of chromosomal loss in PTC that may indicate the inactivation of tumor-suppressor gene loci. Two initial allelotypes of PTC examined showed an insufficient number of chromosomal arms with a low degree of informativity (Matsuo et al., 1991) or no chromosomal arm or locus exhibiting any loss of heterozygosity (LOH) due to small sample size (Kubo et al., 1991). In this study, 30 PTCs were evaluated for microsatellite loss at all autosomal arms, using microsatellite markers with a high degree of informativity to identify novel, frequently occurring areas of chromosomal deletion or imbalance. MATERIAL AND METHODS Tissue and DNA extractionThirty fresh frozen tumor samples were harvested from thyroid resection specimens from patients with PTC. All thyroid resections were done at Johns Hopkins Hospital. Representative sections from tissue used for DNA extraction were stained with hematoxylin and eosin, and diagnosis was confirmed for each lesion by a pathologist (W.W.). Fresh frozen tissue was meticulously dissected on a cryostat to ensure that the specimen contained at least 75% neoplastic cells. Approximately 35 (12 km thick) sections were then collected and placed in SDS/proteinase K at 48°C for 24 hr. DNA was isolated by phenol-chloroform extraction and ethanol precipitation as previously described (van der Riet et al., 1994). Normal control DNA was obtained either by (i) venipuncture and isolation of lymphocyte DNA as previously described (van der Riet et al., 1994), (2) collection of skeletal muscle in the previously mentioned fresh frozen resection specimens followed by DNA isolation or, if necessary, (iii) collection of distant (normal) thyroid tissue from the resection and subsequent DNA isolation. Analysis for allelic losslimbalanceMicrosatellite markers suitable for PC...

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Cytogenetic findings in 31 papillary thyroid carcinomas

Cited by 27 publications

References 29 publications

Fetal adenomas and minimally invasive follicular carcinomas of the thyroid frequently display a triploid or near triploid DNA pattern

Fetal adenomas and minimally invasive follicular carcinomas of the thyroid frequently display a triploid or near triploid DNA pattern

Potent Mitogenicity of the RET/PTC3 Oncogene Correlates with Its Prevalence in Tall-Cell Variant of Papillary Thyroid Carcinoma

An allelotype of papillary thyroid cancer

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