Anaplastic transformation of thyroid cancer: Review of clinical, pathologic, and molecular evidence provides new insights into disease biology and future therapy

Wiseman, Sam M.; Loree, Thom R.; Rigual, Néstor R.; Hicks, Wesley L.; Douglas, Wade G.; Anderson, Garth R.; Stoler, Daniel L.

doi:10.1002/hed.10277

Cited by 102 publications

(62 citation statements)

References 86 publications

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“…25 At the other end of the spectrum, anaplastic thyroid carcinoma is morphologically undifferentiated, clinically aggressive, and fatal in most cases notwithstanding hard-hitting multimodality therapy. 1,2 The relationship between well-differentiated and undifferentiated thyroid carcinoma has long been a point of interest. The current consensus holds that most, if not all, anaplastic thyroid carcinomas arise from a pre-existing well-differentiated thyroid carcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…In reported series, anywhere from 8 to 90% of anaplastic thyroid carcinomas are seen in association with a differentiated carcinoma. 1,3 The direct and casual relationship between well-differentiated and undifferentiated thyroid carcinoma, however, has not been convincingly confirmed at the molecular genetic level. With their complex karyotypes and extensive allelic imbalances, anaplastic thyroid carcinomas show little resemblance to well-differ- entiated thyroid carcinoma, leading some investigators to conclude that anaplastic thyroid carcinomas arise de novo.…”

Section: Discussionmentioning

confidence: 99%

“…1 Yet, despite the presumed close relationship between well-differentiated thyroid carcinoma and its anaplastic counterpart, the contrast between the two is striking. Clinically, anaplastic thyroid carcinoma is a highly aggressive and rapidly fatal.…”

mentioning

confidence: 99%

“…3,4 At the genetic level, anaplastic thyroid carcinoma demonstrates advanced genetic alterations. Compared to well-differentiated carcinomas, anaplastic thyroid carcinomas are more likely to be aneuploid, 5 they demonstrate a much higher prevalence of loss of heterozygosity, 1,6 and they harbor alterations of key regulators of cell growth and differentiation that are not targeted in earlier stages of tumorigenesis. 7,8 As one example, mutations of p53 are commonly noted in anaplastic thyroid carcinomas, but they are rarely present in well-differentiated thyroid carcinomas.…”

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confidence: 99%

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BRAF mutations in anaplastic thyroid carcinoma: implications for tumor origin, diagnosis and treatment

et al. 2004

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Anaplastic thyroid carcinoma is a highly aggressive neoplasm. Affected patients typically present with advanced disease where there is little hope for cure using conventional therapeutic modalities. Understanding the genetic alterations underlying the development of anaplastic thyroid carcinoma, such as mutational activation of BRAF, could help clarify its relationship with well-differentiated forms of thyroid carcinoma (ie follicular and papillary carcinoma) and could help select patients most likely to benefit from novel therapeutic strategies targeting BRAF. We tested 16 anaplastic thyroid carcinomas for the thymine (T)-adenine (A) missense mutation at nucleotide 1796 in the BRAF gene using a newly developed assay that employs a novel primer extension method (Mutector s assay). Seven of these anaplastic thyroid carcinomas arose in association with a well-differentiated thyroid carcinoma, and these were also evaluated. The 1796T-A mutation was detected in eight (50%) of the anaplastic thyroid carcinomas, in four of five (80%) associated papillary thyroid carcinomas, and in zero of two (0%) associated follicular carcinomas. In all seven cases where anaplastic thyroid carcinoma arose in association with a well-differentiated thyroid carcinoma, BRAF status in the two components was concordant. Like papillary thyroid carcinoma, a significant percentage of anaplastic thyroid carcinomas also harbor BRAF mutations. Indeed, when papillary thyroid carcinoma and anaplastic thyroid carcinoma occur together, they consistently share the same BRAF profile, supporting the notion that many anaplastic thyroid carcinomas actually represent progressive malignant degeneration of a pre-existing welldifferentiated thyroid carcinoma. The high frequency of BRAF mutations in a tumor that is generally regarded as uniformly fatal justifies evaluation of the potential benefits of anti-BRAF therapy for patients with anaplastic thyroid carcinoma.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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BRAF mutations in anaplastic thyroid carcinoma: implications for tumor origin, diagnosis and treatment

et al. 2004

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“…Very few anaplastic thyroid cancer patients survive longer than a year, and report of longterm survivors casts doubt on the validity of their diagnosis [5,6]. Passler and coworkers [7] found that irrespective of the surgical approach used, 5-year survival rate ranges from 4% to 8%.…”

Section: Discussionmentioning

confidence: 99%

Immunoexpression of TTF-1 and Ki-67 in a coexistent anaplastic and follicular thyroid cancer with rare long-life surviving.

Ziad

Ruchała²,

Bręborowicz³

et al. 2009

Folia Histochem Cytobiol.

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Abstract:We report the immunohistochemical diagnosis, including TTF-1 (thyroid transcription factor 1) and Ki-67, of a rare mixed thyroid neoplasm composed of minimally invasive well differentiated follicular areas and highly aggressive undifferentiated anaplastic areas. A 75 old female presented to our clinic with a rapidly growing neck mass. Considering the dynamics of the disease and the multiple challenges presented by the patient: advanced age, tumor size, history of a longstanding goiter we decided to transfer her to the department of surgery. The intraoperative findings were an enlarged right lobe with tracheal and surrounding tissues infiltration. Total thyroidectomy, radical neck lymph nodes dissection and tracheostomy were performed. The histopathological and immunohistochemical examination revealed a coexistent anaplastic and follicular thyroid carcinoma. The proliferation index Ki-67, a cell proliferation marker, was found to be significantly higher in the anaplastic areas (30 ± 5%) in the comparison with the follicular areas (2 ± 1%). The evaluation of the thyroid transcription factor 1 (TTF-1) expression revealed a correlation with the tumor cells aggressiveness accordingly to the cancer areas. After a radical surgery an external adjuvant radiation was applied. The patient is alive and more than five years after diagnosis she presented an increase of the serum thyroglobulin level suggesting, probably, a recurrence of the follicular form of the cancer. According to our survey we suggest that in thyroid cancers TTF-1 and Ki-67 could provides useful information on the differentiation activities of thyroid tumor cells and may be helpful to distinguish well differentiated and undifferentiated areas in a mixed thyroid cancer.

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Identification of Molecular Markers Altered During Transformation of Differentiated Into Anaplastic Thyroid Carcinoma

Wiseman

Griffith²,

Deen³

et al. 2007

Arch Surg

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Anaplastic transformation of thyroid cancer: Review of clinical, pathologic, and molecular evidence provides new insights into disease biology and future therapy

Abstract: It is based on an understanding of this process that effective treatments for this aggressive malignancy are currently being developed.

Cited by 102 publications

References 86 publications

BRAF mutations in anaplastic thyroid carcinoma: implications for tumor origin, diagnosis and treatment

BRAF mutations in anaplastic thyroid carcinoma: implications for tumor origin, diagnosis and treatment

Immunoexpression of TTF-1 and Ki-67 in a coexistent anaplastic and follicular thyroid cancer with rare long-life surviving.

Identification of Molecular Markers Altered During Transformation of Differentiated Into Anaplastic Thyroid Carcinoma

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