Diagnostic Value of Differential Expression of CK19, Galectin-3, HBME-1, ERK, RET, and p16 in Benign and Malignant Follicular-Derived Lesions of the Thyroid: An Immunohistochemical Tissue Microarray Analysis

Barroeta, Julieta E.; Baloch, Zubair W.; Lal, Priti; Pasha, Theresa L.; Zhang, P. J.; LiVolsi, Virginia A.

doi:10.1385/ep:17:3:225

Cited by 104 publications

(83 citation statements)

References 39 publications

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“…It has been reported that a target of CBX7 would be the CDKN2A/p16 tumor suppressor gene (11,12,33), suggesting that overexpression of CBX7 could enable cells to evade oncogeneinduced senescence; we then evaluated CDKN2A/p16 expression in (34,35), we show that CDKN2A/p16 is moderately overexpressed in PTCs and highly overexpressed in ATCs compared with normal thyroid tissues (Fig. 5).…”

Section: Cbx7 In Thyroid Carcinomasmentioning

confidence: 82%

Loss of the CBX7 Gene Expression Correlates with a Highly Malignant Phenotype in Thyroid Cancer

et al. 2008

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Using gene expression profiling, we found that the CBX7 gene was drastically down-regulated in six thyroid carcinoma cell lines versus control cells. The aims of this study were to determine whether CBX7 is related to the thyroid cancer phenotype and to try to identify new tools for the diagnosis and prognosis of thyroid cancer. We thus evaluated CBX7 expression in various snap-frozen and paraffin-embedded thyroid carcinoma tissues of different degrees of malignancy by quantitative reverse transcription-PCR and immunohistochemistry, respectively. CBX7 expression progressively decreased with malignancy grade and neoplasia stage. Indeed, it decreased in an increasing percentage of cases going from benign adenomas to papillary (PTC), follicular, and anaplastic (ATC) thyroid carcinomas. This finding coincides with results obtained in rat and mouse models of thyroid carcinogenesis. CBX7 loss of heterozygosity occurred in 36.8% of PTC and in 68.7% of ATC. Restoration of CBX7 expression in thyroid cancer cells reduced growth rate, with a retention in the G 1 phase of the cell cycle, suggesting that CBX7 can contribute to the proliferation of the transformed thyroid cells. In conclusion, loss of CBX7 expression correlates with a highly malignant phenotype in thyroid cancer patients. [Cancer Res 2008;68(16):6770-8]

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Section: Cbx7 In Thyroid Carcinomasmentioning

confidence: 82%

Loss of the CBX7 Gene Expression Correlates with a Highly Malignant Phenotype in Thyroid Cancer

et al. 2008

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“…This low specificity makes the clinical application of Gal-3 debated and prompted several researchers to search for other markers to be used alone or in combination. The combined analysis of Gal-3 and cytokeratin-19, fibronectin-1, or HBME-1 has previously been investigated, demonstrating its value when applied to inconclusive FNAB (Prasad et al 2005, Saggiorato et al 2005, Barroeta et al 2006. However, those studies also demonstrated the limits of this analysis in adenomatous hyperplasia where Gal-3 is frequently expressed.…”

Section: Discussionmentioning

confidence: 99%

“…However, more recent studies indicate that the search for Gal-3 protein expression in combination with other markers by immunohistochemical methods may be useful to improve the diagnostic accuracy of FNAB. Immunocytochemical expression of Gal-3, HBME-1, cytokeratin-19, RET, CITED-1, and fibronectin-1 demonstrated that a combination of two or a panel of markers may more effectively distinguish benign from malignant thyroid nodules (Prasad et al 2005, Saggiorato et al 2005, Barroeta et al 2006, Nakamura et al 2006.…”

Section: Introductionmentioning

confidence: 99%

Combined analysis of galectin-3 and BRAFV600E improves the accuracy of fine-needle aspiration biopsy with cytological findings suspicious for papillary thyroid carcinoma

Sapio¹,

Guerra²,

Posca³

et al. 2007

Endocrine Related Cancer

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Ten to fifteen percent of fine-needle aspiration biopsy (FNAB) of thyroid nodules are indeterminate. Galectin-3 (Gal-3) and the oncogene BRAF V600E are markers of malignancy useful to improve FNAB accuracy. The objective of this study was to determine whether the combined analysis of Gal-3 and BRAF V600E expression in thyroid aspirates could improve the diagnosis in FNAB with suspicious cytological findings. Two hundred and sixty-one surgical thyroid tissues and one hundred and forty-four thyroid aspirates were analyzed for the presence of the two markers. In surgical specimens, Gal-3 expression was present in 27.4% benign nodules, 91.9% papillary (PTC) and 75% follicular (FTC) thyroid carcinomas. BRAF V600E was not detected in 127 benign nodules, as well as in 32 FTCs, while was found in 42.9% PTC. No correlation was found between BRAF mutation and Gal-3 expression. Forty-seven consecutive FNAB suspicious for PTC were analyzed for the presence of the two markers. Of these nodules, 23 were benign at histology, 6 were positive for Gal-3, none displayed BRAF V600E, and 17 were negative for both the markers. Twenty suspicious nodules were diagnosed as PTC and four FTCs at histology. Of these 24 carcinomas, 9 resulted positive for BRAF V600E, 17 for Gal-3, and 22 for one or both the markers. The sensitivity, specificity, and accuracy for the presence of Gal-3 and/or BRAF V600E were significantly higher than those obtained for the two markers alone. Notably, the negative predictive value increased from 70.8 to 89.5%. In conclusion, the combined detection of Gal-3 and BRAF V600E improves the diagnosis in FNAB with cytological findings suspicious for PTC and finds clinical application in selected cases.

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“…The Hector Battifora mesothelial antigen-1 (HBME-1) and Cytokeratin-19 (CK-19) have been the most commonly studied adjunctive markers to Gal-3. Their use has often enhanced the sensitivity and specificity for distinguishing between benign and malignant thyroid lesions, when compared with Gal-3 alone, although this difference was usually small 84,91,93,96 (Table 2). Furthermore, in a recent review of marker panel studies for thyroid cancer diagnosis reported by our group, Gal-3 was often identified as a top performer, and in several cases, the individual performance of Gal-3 was better than any other marker combination investigated.…”

Section: Immunopanel Evaluation With Gal-3mentioning

confidence: 99%

Diagnostic Utility of Galectin-3 in Thyroid Cancer

Chiu

Strugnell

Griffith

et al. 2010

The American Journal of Pathology

135

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Galectin-3 (Gal-3), which has received significant recent attention for its utility as a diagnostic marker for thyroid cancer, represents the most well-studied molecular candidate for thyroid cancer diagnosis. Gal-3 is a protein that binds to ␤-galactosidase residues on cell surface glycoproteins and has also been identified in the cytoplasmic and nuclear compartment. This marker has been implicated in regulation of normal cellular proliferation and apoptosis, as well as malignant transformation and the metastasis of cancer cells. We here present a mechanistic review of Gal-3 and its role in cancer development and progression. Gal-3 expression studies in thyroid tissue and cytologic tumor specimens and their methodological considerations are also discussed in this article. Despite great variance in their methodology, the majority of immunohistochemical studies found that Gal-3 was differentially expressed in thyroid carcinoma compared with benign and normal thyroid specimens, suggesting that Gal-3 is a good diagnostic marker for thyroid cancer. Recent studies have also demonstrated improved methodological reliability. On the other hand, Gal-3 genomic expression studies have shown inconsistent results for diagnostic utility and are not recommended. Overall, the development of Gal-3 as a diagnostic marker for thyroid cancer represents a promising avenue for future study, and its clinical application could significantly reduce the number of diagnostic thyroid operations performed for cases of indeterminant fine needle aspiration biopsy cytology, and thus positively impact the current management of thyroid nodular disease. (Am J

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Diagnostic Value of Differential Expression of CK19, Galectin-3, HBME-1, ERK, RET, and p16 in Benign and Malignant Follicular-Derived Lesions of the Thyroid: An Immunohistochemical Tissue Microarray Analysis

Abstract: HBME-1, ERK, and p16 were more specific for malignancy, whereas CK19 and GAL-3 stained benign lesions with a higher frequency and were not specific for malignant FDLT. RET-oncoprotein showed poor sensitivity and specificity.

Cited by 104 publications

References 39 publications

Loss of the CBX7 Gene Expression Correlates with a Highly Malignant Phenotype in Thyroid Cancer

Loss of the CBX7 Gene Expression Correlates with a Highly Malignant Phenotype in Thyroid Cancer

Combined analysis of galectin-3 and BRAFV600E improves the accuracy of fine-needle aspiration biopsy with cytological findings suspicious for papillary thyroid carcinoma

Diagnostic Utility of Galectin-3 in Thyroid Cancer

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