Clear Cell Change in Thyroid Carcinoma: A Clinicopathologic and Molecular Study with Identification of Variable Genetic Anomalies

Ede

2019

Genes

The dynamic and never exactly repeatable tumor transcriptomic profile of people affected by the same form of cancer requires a personalized and time-sensitive approach of the gene therapy. The Gene Master Regulators (GMRs) were defined as genes whose highly controlled expression by the homeostatic mechanisms commands the cell phenotype by modulating major functional pathways through expression correlation with their genes. The Gene Commanding Height (GCH), a measure that combines the expression control and expression correlation with all other genes, is used to establish the gene hierarchy in each cell phenotype. We developed the experimental protocol, the mathematical algorithm and the computer software to identify the GMRs from transcriptomic data in surgically removed tumors, biopsies or blood from cancer patients. The GMR approach is illustrated with applications to our microarray data on human kidney, thyroid and prostate cancer samples, and on thyroid, prostate and blood cancer cell lines. We proved experimentally that each patient has his/her own GMRs, that cancer nuclei and surrounding normal tissue are governed by different GMRs, and that manipulating the expression has larger consequences for genes with higher GCH. Therefore, we launch the hypothesis that silencing the GMR may selectively kill the cancer cells from a tissue.

Section: Resultsmentioning

confidence: 99%

The Gene Master Regulators (GMR) Approach Provides Legitimate Targets for Personalized, Time-Sensitive Cancer Gene Therapy

Ede

2019

Genes

The Kaohsiung J of Med Scie

“…The etiology and pathogenesis of thyroid cancer are still unclear. Multiple clinical treatment methods, including surgical resection, molecularly targeted tumor therapy, immune gene therapy and other methods have been developed in the recent years [1,22]. However, due to recurrence and metastasis, the final treatment effects are not satisfactory.…”

Section: Discussionmentioning

confidence: 99%

“…Thyroid carcinoma is the most common malignant tumor in the endocrine system [1,2]. The incidence of papillary thyroid cancer (PTC) is the highest among all thyroid malignancies and accounts for more than 80% of thyroid cancers [3].…”

Section: Introductionmentioning

confidence: 99%

Ginsenoside improves papillary thyroid cancer cell malignancies partially through upregulating connexin 31

Chen

et al. 2018

Connexin 31 (Cx31) is considered a suppressor for many tumors. Ginsenoside (Rg1) is a traditional Chinese herb that is widely acknowledged due to its anti-tumor characteristics. However, limited studies have focused on the role of Rg1 in papillary thyroid cancer (PTC) cells. In the current study, we found that the expression of Cx31 in thyroid cancer tissues and thyroid cancer cell lines was significantly lower than that in normal thyroid epithelial tissues and cell lines. Overexpression of Cx31 reduced thyroid cancer cell proliferation, migration and invasion. Furthermore, we found that Rg1 significantly enhanced the expression of Cx31. Moreover, the proliferation and migration of IHH-4 and BCPAP cells were significantly reduced by Rg1 treatment. In contrast, the silencing of Cx31 enhanced the expression of Ki67 and proliferating cell nuclear antigen (PCNA). Meanwhile, treatment with Rg1 significantly decreased the protein levels of Ki67 and PCNA, but these effects could be abolished by transfection with si-Cx31. In summary, we provide novel evidence that the expression of Cx31 was decreased in thyroid cancer cells, but Rg1 treatment could significantly enhance the expression of Cx31 thereby suppressing thyroid cancer cell proliferation and migration.

“…[1][2][3][4][5][6] The most comprehensive studies yet report clear cell change in frequencies ranging from less than 1% to 3% of primary thyroid carcinomas (most often in FTCs, more seldom in PTCs). [2][3][4][5][6][7][8] The reason for the clear cell phenotype is believed to be intracytoplasmic deposits of glycogen, lipids or colloid vacuoles, but the causal mechanism for this aberrancy is not fully elucidated. 6,9 For ccFTCs, the underlying genetics partly mirrors the findings in conventional follicular tumors, with RAS mutations and PAX8-PPARG rearrangements reported, but also surprisingly TP53 mutations in individual cases.…”

Section: Introductionmentioning

confidence: 99%

“…8,10 The histologic manifestation of clear cell change seems to carry little prognostic implication but could constitute a major differential diagnostic problem for both cytologists and pathologists. 1,8,11 Especially, medullary thyroid carcinoma, metastatic renal cell and parathyroid carcinoma must be ruled out before a diagnosis of a clear cell follicular thyroid tumor can be established. 1 In this report, we present a rather unique finding of a clear cell variant follicular thyroid tumor with uncertain malignant potential (ccFT-UMP).…”

Section: Introductionmentioning

confidence: 99%

Clear Cell Variant of a Follicular Thyroid Tumor With Uncertain Malignant Potential: A Case Report

et al. 2018

Follicular neoplasms of the thyroid gland are most often characterized by follicular-patterned thyrocytes with a neutrally stained cytoplasm, while a minority of cases present with oncocytic differentiation (Hürthle cell tumors). Exceedingly rare variants with a clear cell phenotype have also been reported, both as clear cell follicular thyroid adenomas (ccFTAs) and clear cell follicular carcinomas (ccFTCs). We present a patient with a 30-mm lesion in the thyroid isthmus in which the preoperative cytology proposed a follicular tumor. On postoperative histopathological evaluation, the tumor surprisingly displayed uniform clear-cell differentiation. No nuclear features suggestive of papillary thyroid carcinoma were observed, and differential diagnoses such as medullary thyroid carcinoma, metastatic renal cell, and parathyroid carcinoma were ruled out. The histological investigation revealed intracapsular collections of tumor cells displaying a debatable relation to the surrounding capsule and blood vessels, and the final diagnosis was a follicular tumor of uncertain malignant potential (FT-UMP) as defined by the WHO 2017 classification. As subsets of FT-UMPs with TERT promoter mutations do recur as advanced malignant tumors, a sequencing analysis was undertaken but could not identify TERT promoter mutations at position C228 or C250. To our knowledge, no previous literature has described a clear cell phenotype in an FT-UMP. We therefore advocate that endocrine pathologists should be aware of this entity in addition to ccFTAs and ccFTCs.