Expression of MRP1 and ABCG2 is associated with adverse clinical outcomes of papillary thyroid carcinoma with a solid component

Ohashi, Ryuji; Kawahara, Kiyoko; Namimatsu, Shigeki; Okamura, Ritsuko; Igarashi, Takehito; Sugitani, Iwao; Naito, Zenya

doi:10.1016/j.humpath.2017.03.012

Cited by 25 publications

(11 citation statements)

References 26 publications

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“…Kakudo et al reported that Ki67 labeling index >10% can be a predictor of aggressive thyroid tumors including PDTC [41]. We recently demonstrated that expression levels of both CK19 and HBME1 were lower in solid nests than in papillary components within the tumor of SVPTC [42]. We further found that SVPTC cases with lower expression of CK19 and HBME1 was more likely to have a tumor recurrence after surgery.…”

Section: Immunohistochemical Profilessupporting

confidence: 51%

“…Yun et al A found that a higher expression of ATP-binding cassette G2 (ABCG2) and multidrug resistance associated protein 1 (MRP1), a candidate for CSC marker, was related to shorter overall survival in patients with ATC [38]. Likewise, we recently reported that expression of ABCG2 and MRP1 is immunohistochemically increased in solid components of SVPTC and its expression levels correlate with poor prognosis [42].…”

Section: Immunohistochemical Profilesmentioning

confidence: 95%

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Solid variant of papillary thyroid carcinoma: an under-recognized entity

Ohashi

2020

Endocr J

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Solid variant of papillary thyroid carcinoma (SVPTC) is a rare morphological variant of papillary thyroid carcinoma (PTC). SVPTC is histologically characterized by predominant solid, trabecular and insular nests of tumor cells while cytological features of PTC such as nuclear grooves and nuclear inclusions are preserved. In fine needle aspiration cytology smears, tumor cells of SVPTC may be presented in cohesive, syncytial or trabecular clusters accompanied by some discohesiveness in the absence of necrosis. Although SVPTC and poorly differentiated thyroid carcinoma (PDTC) share similar histological findings of solid nests, SVPTC can be differentiated from PDTC in the lack of tumor necrosis, severe nuclear atypia, and a higher mitotic index. Immunohistochemical expression of CK19 and HBME-1, common markers of PTC, is decreased in solid nests of SVPTC. In pediatric patients exposed to radiation after the Chernobyl nuclear accident, there was a higher prevalence of SVPTC with RET/PTC3 type rearrangement. BRAF mutations are also reported in a small number of adult patients with SVPTC without any prior radiation exposure. Patients with SVPTC may have a slightly higher incidence of metastasis and recurrence of the tumor compared to conventional PTC, although overall survival rate is comparable. In this article, the current knowledge of SVPTC will be reviewed and discussed with an emphasis on the histopathological feature.

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Section: Immunohistochemical Profilessupporting

confidence: 51%

Section: Immunohistochemical Profilesmentioning

confidence: 95%

Solid variant of papillary thyroid carcinoma: an under-recognized entity

Ohashi

2020

Endocr J

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“…Indeed, recent studies have shown that the presence of the solid component in PTC, regardless of the proportion, is associated with adverse clinical parameters and a shorter disease-free survival [ 26 , 27 ]. At a molecular level, the solid component is enriched in the expression of cancer stem cell markers ATP-binding cassette G2 (ABCG2) and multidrug resistance associated protein 1 (MRP1) that were absent or significantly lower expressed in the papillary component of the same tumor, whereas they are frequently overexpressed in ATC and are related to adverse clinical outcomes [ 28 , 29 ]. This is consistent with the idea that the solid component is less differentiated and may be a progression toward a poorly differentiated or anaplastic phenotype.…”

Section: Discussionmentioning

confidence: 99%

Loss of One or Two PATZ1 Alleles Has a Critical Role in the Progression of Thyroid Carcinomas Induced by the RET/PTC1 Oncogene

Monaco

Palma

Vitiello

et al. 2018

Cancers

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POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) is an emerging cancer-related gene that is downregulated in different human malignancies, including thyroid cancer, where its levels gradually decrease going from papillary thyroid carcinomas (PTC) to poorly differentiated and undifferentiated highly aggressive anaplastic carcinomas (ATC). The restoration of PATZ1 expression in thyroid cancer cells reverted their malignant phenotype by inducing mesenchymal-to-epithelial transition, thus validating a tumor suppressor role for PATZ1 and suggesting its involvement in thyroid cancer progression. Here, we investigated the consequences of the homozygous and heterozygous loss of PATZ1 in the context of a mouse modeling of PTC, represented by mice carrying the RET/PTC1 oncogene under the thyroid specific control of the thyroglobulin promoter RET/PTC1 (RET/PTC1TG). The phenotypic analysis of RET/PTC1TG mice intercrossed with Patz1-knockout mice revealed that deficiency of both Patz1 alleles enhanced thyroid cancer incidence in RET/PTC1TG mice, but not the heterozygous knockout of the Patz1 gene. However, both RET/PTC1TG;Patz1+/− and RET/PTC1TG;Patz1−/− mice developed a more aggressive thyroid cancer phenotype—characterized by higher Ki-67 expression, presence of ATCs, and increased incidence of solid variants of PTC—than that shown by RET/PTC1TG; Patz1+/+ compound mice. These results confirm that PATZ1 downregulation has a critical role in thyroid carcinogenesis, showing that it cooperates with RET/PTC1 in thyroid cancer progression.

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“…In addition, ABCG2 was identified as a marker for cancer stem cells (CSCs) [24, 72], which are believed to have a critical role in tumorigenesis and metastasis [61]. One study demonstrated that the overexpression of ABCG2 caused by drug selection regimens contributes to “stem cell-like” properties in multidrug-resistant breast cancer cell lines [10], further suggesting that ABCG2 may play a protective role in the survival of CSCs [29, 36, 71]. More importantly, high ABCG2 expression has been linked to poor clinical outcomes especially in patients with lung carcinoma [29], esophageal squamous cell carcinoma [23, 58] and acute myeloid leukemia (AML) [14, 15, 51, 60].…”

Section: Discussionmentioning

confidence: 99%

Tyrphostin RG14620 selectively reverses ABCG2-mediated multidrug resistance in cancer cell lines

Hsiao

Murakami

et al. 2017

Cancer Letters

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The multidrug resistance (MDR) phenotype associated with the overexpression of ATP-binding cassette (ABC) drug transporters ABCB1, ABCC1 and ABCG2 is a major obstacle in cancer chemotherapy. Numerous epidermal growth factor receptor (EGFR) inhibitors have previously been shown capable of reversing MDR in ABCG2-overexpressing cancer cells. However, most of them are not transporter-specific due to the substantial overlapping substrate specificity among the transporters. In this study, we investigated the interaction between ABCG2 and tyrphostin RG14620, an EGFR inhibitor of the tyrphostin family, in multidrug-resistant cancer cell lines. We found that at nontoxic concentrations, tyrphostin RG14620 enhances drug-induced apoptosis and restores chemosensitivity to ABCG2-overexpressing multidrug-resistant cancer cells. More importantly, tyrphostin RG14620 is selective to ABCG2 relative to ABCB1 and ABCC1. Our findings were further supported by biochemical assays demonstrating that tyrphostin RG14620 stimulates ATP hydrolysis and inhibits photoaffinity labeling of ABCG2 with IAAP, and by a docking analysis of tyrphostin RG14620 in the drug-binding pocket of this transporter. Taken together, our findings indicate that tyrphostin RG14620 is a potent and selective modulator of ABCG2 that may be useful to overcome chemoresistance in patients with drug-resistant tumors.

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Expression of MRP1 and ABCG2 is associated with adverse clinical outcomes of papillary thyroid carcinoma with a solid component

Cited by 25 publications

References 26 publications

Solid variant of papillary thyroid carcinoma: an under-recognized entity

Solid variant of papillary thyroid carcinoma: an under-recognized entity

Loss of One or Two PATZ1 Alleles Has a Critical Role in the Progression of Thyroid Carcinomas Induced by the RET/PTC1 Oncogene

Tyrphostin RG14620 selectively reverses ABCG2-mediated multidrug resistance in cancer cell lines

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