Molecular Evidence for the Same Clonal Origin of Multifocal Papillary Thyroid Carcinomas

McCarthy, Ryan P.; Wang, Mingsheng; Jones, Timothy D.; Strate, Randall W.; Liu, Cheng

doi:10.1158/1078-0432.ccr-05-2818

Cited by 85 publications

(56 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although the study by McCarthy et al (19) reported that multifocality is highly homologous within the gland and is not associated with tumor invasion, Shindo et al (17) and Chow et al (20) found that neck lymph node metastasis and tumor multifocality remain significantly correlated, which is the major reason for lymph node metastasis. The present study is consistent with their findings.…”

Section: Discussionmentioning

confidence: 98%

Outcome of papillary thyroid microcarcinoma: Study of 1,990 cases

Zhang

Wei

et al. 2015

Molecular and Clinical Oncology

View full text Add to dashboard Cite

Abstract. The present study examines the requirement of prophylactic neck node dissection in papillary thyroid microcarcinoma (PTMC) patients by analyzing high-risk factors of neck lymph node metastasis in PTMC. The clinical pathological data was a review of 1,990 patients diagnosed between January 2013 and January 2014. The data included information on patient gender, age, tumor size, multifocal, tumor pathological staging, bilateral thyroid cancer, the subtypes, BRAF V600E mutation, human telomerase reverse transcriptase (hTERT), extrathyroidal invasion and neck lymph node metastasis. The univariate analysis (χ 2 test) showed that a number of factors were significantly associated with neck lymph node metastasis in PTMC (P<0.05): Male gender, aged <45 years, extrathyroidal invasion, bilateral thyroid cancer, various subtypes (package type, follicular variant, diffuse sclerosing variant, eosinophils, tall cell and column variant), BRAF V600E mutation-positive, hTERT mutation-positive, pt3/4 and multifocality. The multivariate analysis (regression binary logistic) showed that the male gender, <45 years, tumor size >5 mm, extrathyroidal invasion, bilateral thyroid tumors, multifocality, BRAF V600E mutation-positive, hTERT mutation-positive and pt3/4 are associated with the neck lymph node metastasis in PTMC (P<0.05). These paired analysis results show that the subtypes of PTMC with tumor size >5 mm is more common than the specific types of PTMC in which the tumor is ≤5 mm in neck lymph node metastasis. The neck lymph node metastasis incidence of the >45 years age group patients without high-risk factors in PTMC is 8.13 and 6.80%, respectively. In conclusion, PTMC patients with high-risk factors only are recommended to undergo a prophylactic lymph node dissection.

show abstract

Section: Discussionmentioning

confidence: 98%

Outcome of papillary thyroid microcarcinoma: Study of 1,990 cases

Zhang

Wei

et al. 2015

Molecular and Clinical Oncology

View full text Add to dashboard Cite

show abstract

“…26,28 The clonality of the samples was evaluated on the basis of a polymorphism of the X-linked human androgen receptor gene (HUMARA) locus. 26,[28][29][30] This technique is dependent on digestion of DNA with the methylation-sensitive restriction enzyme HhaI, PCR amplification of the HUMARA locus and the detection of methylation at this locus. With this method, only the methylated HUMARA allele is amplified by PCR.…”

Section: Detection Of X-chromosome Inactivationmentioning

confidence: 99%

Inverted papilloma of the urinary bladder: a molecular genetic appraisal

et al. 2006

Self Cite

View full text Add to dashboard Cite

Inverted papilloma of urinary bladder is an uncommon urothelial neoplasm. Its relationship to urothelial carcinoma is controversial. Little is known of the genetic abnormalities of inverted papilloma. To better understand its genetics, we analyzed 39 inverted papillomas, including 36 from men and three from women, for loss of heterozygosity (LOH). We examined four polymorphic microsatellite markers located on chromosome 9q32-33(D9S177), chromosome 9p22 (IFNA), chromosome 3p14.2 (D3S1300) and chromosome 17p13.1 (TP53), where genetic alterations occur frequently in urothelial carcinomas. Additionally, the status of inactivation of X-chromosome was examined in three female patients. The frequency of LOH in informative cases was 8% (3 of 37) for D9S177, 10% (4 of 38) for TP53, 8% (3 of 37) for IFNA and 8% (3 of 36) for D3S1300. In the analysis of X-chromosome inactivation, all three cases yielded informative results and one had nonrandom inactivation of X-chromosomes. The monoclonal origin demonstrated in the study of X-chromosome inactivation indicates the clonal process of inverted papilloma; however, the low incidence of LOH supports the view that inverted papilloma in urinary bladder is a benign neoplasm with molecular genetic abnormalities different from those of urothelial carcinoma.

show abstract

“…It was reported that multifocal PTC was more likely to have nodal and pulmonary metastases, as well as persistent disease (Mazzaferri et al 1977). X-chromosome inactivation in female cases and a narrow panel of loss of heterozygosity (LOH) were used to identify the clonality of multifocal PTC and 50-87% of the cases were found to arise from the same clone (Shattuck et al 2005, McCarthy et al 2006. The importance to separate multifocal independent primary (IP) PTC from PTC with intrathyroid metastasis is unclear.…”

Section: Introductionmentioning

confidence: 99%

Molecular analysis of multifocal papillary thyroid carcinoma

Lin¹,

Finkelstein²,

Zhu³

et al. 2008

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

Papillary thyroid carcinoma (PTC) frequently presents as a multifocal process. To study the importance of separating independent primary (IP) from intrathyroid metastatic (ITM) PTC, we examined 19 molecular markers on 42 separate tumors from 18 multifocal PTC cases. In 12 of 18 (66 . 7%) cases, including 6 of 12 (50%) papillary microcarcinoma cases, the same or similar profile of loss of heterozygosities (LOH) and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation was demonstrated, indicating that they were from the same primary and represented ITM. Different profiles of LOHs and BRAF mutation were detected in separate tumors of 6 of 18 cases, indicating that they represented IP. Patients with ITM, including papillary microcarcinoma, had significantly increased lymph node metastasis. The frequencies of LOHs of 17q21, 17p13, 10q23, and 22q13 were higher in tumors with lymph node metastasis, suggesting that these LOHs may be important in increased lymph node metastasis. LOH of 9p21 was found at the highest frequency in PTC (53 . 8%), followed by 1p36 (46 . 2%), 10q23 (34 . 6%), and 22q13 (34 . 6%). Papillary microcarcinoma had acquired similar genomic mutations as conventional PTC, but higher frequencies of mutations of BRAF, 1p36, 18q, and 22q13 were found in the larger PTC, suggesting that they might play a role in the aggressiveness of PTC. Different profiles of mutations were observed in conventional, follicular variants, and diffuse sclerosing variant of PTC, which might influence the different morphological appearances and clinical courses. In conclusion, molecular analysis can separate multifocal IP PTC from ITM PTC, and may be more important than tumor size in predicting lymph node metastasis, aggressiveness, and prognosis of PTC.

show abstract

Molecular Evidence for the Same Clonal Origin of Multifocal Papillary Thyroid Carcinomas

Cited by 85 publications

References 30 publications

Outcome of papillary thyroid microcarcinoma: Study of 1,990 cases

Outcome of papillary thyroid microcarcinoma: Study of 1,990 cases

Inverted papilloma of the urinary bladder: a molecular genetic appraisal

Molecular analysis of multifocal papillary thyroid carcinoma

Contact Info

Product

Resources

About