Anaplastic thyroid carcinoma: review of treatment protocols

Tiedje, Vera; Stuschke, Martin; Weber, Frank; Dralle, Henning; Moss, Laura; Führer, Dagmar

doi:10.1530/erc-17-0435

Cited by 85 publications

(68 citation statements)

References 46 publications

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“…22,23 Indeed, the median overall survival has not changed in the last decades. 24,25 It is well recognized that EMT represents a major mechanism of tumor progression and, in particular, in thyroid carcinogenesis. [26][27][28] Here, through an EMT profiler array, we found that JAM-A was one of the most downregulated genes in ATC and this was confirmed at the protein level.…”

Section: In Breast Cancers Both Overexpression and Downregulation Ofmentioning

confidence: 99%

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Junctional adhesion molecule‐A is down‐regulated in anaplastic thyroid carcinomas and reduces cancer cell aggressiveness by modulating p53 and GSK3 α/β pathways

Orlandella

Mariniello

Iervolino

et al. 2019

Molecular Carcinogenesis

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Junctional adhesion molecule A (JAM‐A) is a transmembrane protein that contributes to different biological process, including the epithelial to mesenchymal transition (EMT). Through an EMT profiler array, we explored the molecular players associated with human thyroid cancer progression and identified JAM‐A as one of the genes mostly deregulated. The quantitative real‐time polymerase chain reaction and immunohistochemistry analyses showed that downregulation of JAM‐A occurred in anaplastic thyroid carcinoma (ATC) compared with normal thyroid (NT) and papillary thyroid carcinoma (PTC) tissues and correlated with extrathyroid infiltration, tumor size, and ATC histotype. In ATC cell lines, JAM‐A restoration suppressed malignant hallmarks of transformation including cell proliferation, motility, and transendothelial migration. Accordingly, knockdown of JAM‐A enhanced thyroid cancer cell proliferation and motility in PTC cells. Through the proteome profiler human phospho‐kinase array, we demonstrated that higher expression of JAM‐A was associated with a significant increased level of phosphorylation of p53 and GSK3 α/β proteins. In conclusion, our findings highlight a novel role of JAM‐A in thyroid cancer progression and suggest that JAM‐A restoration could have potential clinical relevance in thyroid cancer treatment.

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Section: In Breast Cancers Both Overexpression and Downregulation Ofmentioning

confidence: 99%

“…Currently, there aren't any effective therapies for this disease . Indeed, the median overall survival has not changed in the last decades …”

Section: Introductionmentioning

confidence: 99%

Junctional adhesion molecule‐A is down‐regulated in anaplastic thyroid carcinomas and reduces cancer cell aggressiveness by modulating p53 and GSK3 α/β pathways

Orlandella

Mariniello

Iervolino

et al. 2019

Molecular Carcinogenesis

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“…Furthermore, analysis of different thyroid tumor entities revealed significant higher expression of CD1d and CD1d mRNA in ATCs compared to normal thyroid tissue and all other thyroid tumor types. On average, patients with ATCs survive only a few months after primary diagnosis . Although radiotherapy and different chemotherapies result in slightly improved survival rates, outcome is still very poor .…”

Section: Discussionmentioning

confidence: 99%

“…On average, patients with ATCs survive only a few months after primary diagnosis . Although radiotherapy and different chemotherapies result in slightly improved survival rates, outcome is still very poor . Therefore, several treatment strategies are currently under research .…”

Section: Discussionmentioning

confidence: 99%

“…Although radiotherapy and different chemotherapies result in slightly improved survival rates, outcome is still very poor . Therefore, several treatment strategies are currently under research . Regarding cancer therapy, in the last few years a lot of effort was put into the research of immunotherapy with NKT cells, for which CD1d serves as target receptor .…”

Section: Discussionmentioning

confidence: 99%

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Increased cytoplasmatic expression of cancer immune surveillance receptor CD1d in anaplastic thyroid carcinomas

et al. 2019

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Background Anaplastic thyroid carcinomas are associated with rapid tumor growth, short survival time and without any promising therapy to improve the poor prognosis. In this study, expression of immunoregulative receptor CD1d and lymphocyte infiltration in different thyroid tumors as well as in healthy tissue were analyzed in order to find new targets for an immunotherapeutic approach. Methods CD1d immunohistochemistry was performed in samples of 18 anaplastic, 17 follicular, 27 papillary, and 4 medullary thyroid carcinomas as well as in 19 specimens from normal thyroid tissue and additionally in 10 samples of sarcoma, seven malignant melanoma and three spindle‐cell lung carcinoma. Furthermore, thyroid samples were stained with antibodies against CD3, CD20, CD56, CD68, and LCA in order to analyze lymphocyte infiltration. Results For the first time CD1d receptor expression on normal thyroid tissue could be demonstrated. Moreover, anaplastic thyroid carcinomas showed significantly higher expression levels compared to other thyroid samples. Most astonishingly, CD1d expression disappeared from the cellular surface and was detected rather in the cytoplasm of anaplastic thyroid carcinoma cells. In addition, histologically similar tumors to anaplastic carcinoma like sarcoma and malignant melanoma revealed distinct CD1d staining patterns. Furthermore, infiltration of T cells, B cells, and macrophages in anaplastic thyroid carcinomas was different when compared to normal thyroid tissue and all other thyroid carcinomas. Conclusions Anaplastic thyroid carcinomas show significantly higher expression of CD1d, a receptor for NKT cells, which are subject of several anticancer therapy studies. These results may offer a novel approach to explore immunotherapeutic treatment options.

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Response to neoadjuvant paclitaxel predicts survival in anaplastic thyroid carcinoma

et al. 2022

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The clinical utilities of paclitaxel in anaplastic thyroid carcinoma (ATC) have been reported. The current study investigated the outcomes in ATC patients treated by paclitaxel as neoadjuvant setting. Furthermore, the prognostic factor for overall survival (OS) and predictive marker for response to paclitaxel were investigated. Records of ATC patients treated by paclitaxel as neoadjuvant setting in our hospital were reviewed. The median OS for the patients with ( n = 43) and without ( n = 23) resection were 14.7 (95% CI, 11.0–21.7) and 4.2 (95% CI, 3.0–5.4) months, respectively ( p < 0.001). Univariate analysis identified the factors of stage ( p = 0.028), prognostic index (PI) ≥2 ( p < 0.001), response to paclitaxel ( p = 0.007), resection ( p < 0.001), and radiotherapy ( p < 0.001) to be associated with OS, and multivariate analysis revealed that the factors of PI ≥2 [hazard ratio (HR), 2.406 (95% CI, 1.096–5.281), p = 0.029], response to paclitaxel [HR, 0.423 (95% CI, 0.193–0.930), p = 0.032], resection [HR, 0.316 (95% CI, 0.129–0.773), p = 0.012], and radiotherapy [HR, 0.229 (95% CI, 0.100–0.526), p < 0.001] were independent prognostic factors of OS. There were no significant predictive factors for response to paclitaxel in baseline characteristics. PI ≥2, response to paclitaxel, resection, and radiotherapy were independent prognostic factors in ATC patients treated with paclitaxel as neoadjuvant setting. It is important to investigate predictor for response to paclitaxel for improving resectability and prognosis in ATC.

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Anaplastic thyroid carcinoma: review of treatment protocols

Cited by 85 publications

References 46 publications

Junctional adhesion molecule‐A is down‐regulated in anaplastic thyroid carcinomas and reduces cancer cell aggressiveness by modulating p53 and GSK3 α/β pathways

Junctional adhesion molecule‐A is down‐regulated in anaplastic thyroid carcinomas and reduces cancer cell aggressiveness by modulating p53 and GSK3 α/β pathways

Increased cytoplasmatic expression of cancer immune surveillance receptor CD1d in anaplastic thyroid carcinomas

Response to neoadjuvant paclitaxel predicts survival in anaplastic thyroid carcinoma

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