Patterns of expression of cell cycle/apoptosis genes along the spectrum of thyroid carcinoma progression

Saltman, Benjamin; Singh, Bhuvanesh; Hedvat, Cyrus V.; Wreesmann, Volkert B.; Ghossein, Ronald

doi:10.1016/j.surg.2006.07.027

Cited by 60 publications

(44 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…ATC and PDTC were strikingly distinct showing the highest MIB-1 labeling index. Interestingly, a significant progressive increase in MIB-1 along the spectrum of thyroid cancer progression has been described (20). In the case of well differentiated tumors, lower, but overlapping, values between groups were noted in our study.…”

Section: Discussionsupporting

confidence: 72%

Diagnostic and prognostic potential of MIB-1 proliferation index in thyroid fine needle aspiration biopsy

Sofiadis

Tani²,

Foukakis³

et al. 2009

Int J Oncol

View full text Add to dashboard Cite

Abstract. Fine needle aspiration biopsy (FNAB) is the preferred technique for the initial diagnostic evaluation of thyroid lesions, which nevertheless poses a diagnostic challenge for all clinicians involved. The latter necessitates the use of molecular markers on thyroid cytology. MIB-1 is a molecular marker already used in the cytological evaluation of various tumors. In this study, we assessed whether MIB-1 proliferation index adds diagnostic information to the conventional cytological analysis of thyroid nodules and prognostic information in thyroid cancers. MIB-1 index for various thyroid lesions was retrospectively reviewed in a series of 504 patients. Furthermore, the prognostic value of MIB-1 index was investigated for 183 of the patients with papillary thyroid cancer (PTC). MIB-1 index was significantly higher in anaplastic thyroid cancer (ATC) compared to other tumor types (p<0.01). No significant difference in MIB-1 index was observed between thyroid adenomas and follicular carcinomas. In PTC, MIB-1 index equal to or >4% was found to be an independent factor significantly associated with higher risk of distant metastasis and disease-related mortality (p<0.05). Conclusively, this study shows that preoperative MIB-1 index assessment in FNAB of thyroid nodules offers little diagnostic information as far as follicular tumors are concerned. In cases of PTC, though, MIB-1 may serve as a prognostic indicator of disease spreading and poor survival and hence influence the planning of the overall treatment scheme.

show abstract

Section: Discussionsupporting

confidence: 72%

Diagnostic and prognostic potential of MIB-1 proliferation index in thyroid fine needle aspiration biopsy

Sofiadis

Tani²,

Foukakis³

et al. 2009

Int J Oncol

View full text Add to dashboard Cite

show abstract

“…57,58 A positive correlation between the nuclear overexpression of cyclin D1, cellular proliferation, and the proliferation marker, Ki-67, with tumor stage and aggressive biological behavior was reported previously. 31,32,39,[59][60][61][62][63][64] An alteration in the gene encoding cyclin D1 has not been reported in thyroid neoplasia, but a link between aberrant b-catenin expression and upregulation of cyclin D1 has been shown in a variety of neoplasms. [65][66][67] In this study, the nuclear expression of cyclin D1 was markedly increased in the vast majority of indolent and aggressive neoplasms.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological and molecular characterization of nine cases of columnar cell variant of papillary thyroid carcinoma

et al. 2011

View full text Add to dashboard Cite

The majority of papillary thyroid carcinoma is indolent and associated with long-term survival. The columnar cell variant, however, is a rare subtype that is variable in biological behavior; some are clinically aggressive, whereas others are more clinically indolent. Tumor size, tumor circumscription, and encapsulation may influence the behavior of columnar cell carcinomas. Other variables including genetic changes and putative biomarkers associated with malignant growth have not been thoroughly examined in these neoplasms. In this study, nine cases of columnar cell variant of papillary thyroid carcinoma from three institutions were classified as clinically indolent or aggressive based on pathological features, clinical history, and outcome. Indolent tumors were typically small, circumscribed or encapsulated, and from younger female patients, whereas aggressive tumors were large, locally aggressive, associated with regional and distant metastasis, and from older male patients. The missense mutation, V600E in the BRAF oncogene (BRAF V600E ), was detected in three of nine of cases, of which two were clinically aggressive. Immunohistochemical evaluation of neoplasiaassociated markers showed increased nuclear cyclin D1 expression, elevated Ki-67 proliferation indices, and predominantly weak nuclear p53 staining in both indolent and aggressive tumors. Expression of b-catenin was largely restricted to a membranous pattern in both tumor types. Cytoplasmic expression of bcl-2 was overall mildly reduced in indolent neoplasms. Nuclear expression of estrogen and progesterone receptors was increased in both indolent and aggressive neoplasms, but was without sex-or age-related differences; however, whereas progesterone receptor expression was diffuse and strong in clinically indolent carcinomas, its expression was diminished in aggressive neoplasms. Recognition of the clinicopathological characteristics and the molecular and immunophenotypic features of the columnar cell variant of papillary thyroid carcinoma may aid in characterizing neoplasms that behave indolently or aggressively. Keywords: BRAF (BRAF V600E ); b-catenin; columnar cell variant; cyclin D1; papillary thyroid carcinoma Papillary thyroid carcinoma is a common endocrine neoplasm that is typically indolent and associated with long-term survival. This favorable biological behavior reflects the vast majority of conventional and histological variants of well-differentiated papillary thyroid carcinoma. However, a more aggressive tumoral growth characterizes a small subset that behaves more akin to poorly differentiated and undifferentiated thyroid carcinoma. Initially included in this group of aggressive neoplasms, the columnar cell variant is a rare subtype with variable biological behavior. Early reports described tumors with fast growth rates, aggressive local invasion, high rates of recurrence, early metastasis to regional lymph nodes and distant

show abstract

“…The prognosis of thyroid carcinoma varies from the indolent well-differentiated papillary and follicular thyroid carcinomas, with a 30-year mortality rate of approximately 6%, to poorly differentiated thyroid carcinoma, which has a 60% 5-year survival rate, to anaplastic thyroid carcinoma (ATC), which is very aggressive and always fatal in a few months (Saltman et al, 2006). Surgical resection and radioactive iodine can be an effective treatment only for well-differentiated tumors.…”

Section: Introductionmentioning

confidence: 99%

Histone deacetylase inhibitors induce thyroid cancer-specific apoptosis through proteasome-dependent inhibition of TRAIL degradation

et al. 2009

View full text Add to dashboard Cite

Anaplastic thyroid carcinoma (ATC) is considered one of the most aggressive malignancies, having a poor prognosis and being refractory to conventional chemotherapy and radiotherapy. Alteration in histone deacetylase (HDAC) activity has been reported in cancer, thus encouraging the development of HDAC inhibitors, whose antitumor action has been shown in both solid and hematological malignancies. However, the molecular basis for their tumor selectivity is unknown. To find an innovative therapy for the treatment of ATCs, we studied the effects of deacetylase inhibitors on thyroid tumorigenesis models. We show that HDACs 1 and 2 are overexpressed in ATCs compared with normal cells or benign tumors and that HDAC inhibitors induce apoptosis selectively in the fully transformed thyroid cells. Our results indicate that these phenomena are mediated by a novel action of HDAC inhibitors that reduces tumor necrosis factor-related apoptosis-inducing ligand protein degradation by affecting the ubiquitin-dependent pathway. Indeed, the combined treatment with HDAC and proteasome inhibitors results in synergistic apoptosis. These results strongly encourage the preclinical application of the combination deacetylaseproteasome inhibitors for the treatment of ATC.

show abstract

Patterns of expression of cell cycle/apoptosis genes along the spectrum of thyroid carcinoma progression

Cited by 60 publications

References 21 publications

Diagnostic and prognostic potential of MIB-1 proliferation index in thyroid fine needle aspiration biopsy

Diagnostic and prognostic potential of MIB-1 proliferation index in thyroid fine needle aspiration biopsy

Clinicopathological and molecular characterization of nine cases of columnar cell variant of papillary thyroid carcinoma

Histone deacetylase inhibitors induce thyroid cancer-specific apoptosis through proteasome-dependent inhibition of TRAIL degradation

Contact Info

Product

Resources

About