Dataset Information

Cytoplasmic versus nuclear THR alpha expression determines survival of ovarian cancer patients.

ABSTRACT:

Purpose

Thyroid hormone receptors (THR) have manifold functions and are involved in the carcinogenesis of several tumor types. Within this study, we aimed to investigate the expression pattern (nuclear versus cytoplasmic) of the THR alpha and its impact on patients survival in ovarian cancer (OvCa).

Methods

The presence of the thyroid hormone receptors THR?, THR?1 and - 2 was investigated in 156 ovarian cancer samples using immunohistochemistry (IHC) using semi-quantitative immunoreactivity (IR) scores and correlated with clinical, pathological data, subtype of ovarian cancer, clinical data, staining of 20 already described OvCa marker proteins and overall survival (OS).

Results

Among all subtypes of OvCa, clear cell carcinomas showed the highest THR? expression. Furthermore, nuclear THR? was associated with a reduced survival in this subtype. However, nuclear expressed THR?1 turned out to be a positive prognosticator for all subtypes of OvCa patients. Nuclear THR?2 is a positive prognosticator for OvCa patients of the serous subtype. In contrast, cytoplasmic expression THR?2 was associated with a reduced OS in all subtypes of OvCa patients; while, cytoplasmic expression of THR?1 is associated with reduced OS in mucinous OvCa patients only. In addition, THR? expression correlates with gonadotropin receptors, steroid hormone receptors, TA-MUC1 and glycodelin.

Conclusion

Depending on nuclear or cytoplasmic expression, our study shows that THR? and its isoforms 1 and 2 provide different prognostic information for ovarian cancer patients. Further investigations should analyze if THRs may represent new endocrine targets for the treatment of ovarian cancer.

SUBMITTER: Ditsch N

PROVIDER: S-EPMC7324415 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Publications

Cytoplasmic versus nuclear THR alpha expression determines survival of ovarian cancer patients.

Ditsch Nina N Heublein Sabine S Jeschke Udo U Sattler Cornelia C Kuhn Christina C Hester Anna A Czogalla Bastian B Trillsch Fabian F Mahner Sven S Engel Jutta J Mayr Doris D Schmoeckel Elisa E

Journal of cancer research and clinical oncology 20200612 8

<h4>Purpose</h4>Thyroid hormone receptors (THR) have manifold functions and are involved in the carcinogenesis of several tumor types. Within this study, we aimed to investigate the expression pattern (nuclear versus cytoplasmic) of the THR alpha and its impact on patients survival in ovarian cancer (OvCa).<h4>Methods</h4>The presence of the thyroid hormone receptors THRα, THRα1 and - 2 was investigated in 156 ovarian cancer samples using immunohistochemistry (IHC) using semi-quantitative immuno ...[more]

PMID: 32533406

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Project description:We previously showed that nuclear localization of the actin-binding protein, filamin A (FlnA), corresponded to hormone-dependence in prostate cancer. Intact FlnA (280 kDa, cytoplasmic) cleaved to a 90 kDa fragment which translocated to the nucleus in hormone-naïve cells, whereas in hormone-refractory cells, FlnA was phosphorylated, preventing its cleavage and nuclear translocation. We have examined whether FlnA localization determines a propensity to metastasis in advanced androgen-independent prostate cancer.We examined, by immunohistochemistry, FlnA localization in paraffin-embedded human prostate tissue representing different stages of progression. Results were correlated with in vitro studies in a cell model of prostate cancer.Nuclear FlnA was significantly higher in benign prostate (0.6612 +/- 0.5888), prostatic intraepithelial neoplasia (PIN; 0.6024 +/- 0.4620), and clinically localized cancers (0.69134 +/- 0.5686) compared with metastatic prostate cancers (0.3719 +/- 0.4992, P = 0.0007). Cytoplasmic FlnA increased from benign prostate (0.0833 +/- 0.2677), PIN (0.1409 +/- 0.2293), localized cancers (0.3008 +/- 0.3762, P = 0.0150), to metastases (0.7632 +/- 0.4414, P < 0.00001). Logistic regression of metastatic versus nonmetastatic tissue yielded the area under the receiver operating curve as 0.67 for nuclear-FlnA, 0.79 for cytoplasmic-FlnA, and 0.82 for both, indicating that metastasis correlates with cytoplasmic to nuclear translocation. In vitro studies showed that cytoplasmic localization of FlnA induced cell invasion whereas nuclear translocation of the protein inhibited it. FlnA dephosphorylation with the protein kinase A inhibitor H-89 facilitated FlnA nuclear translocation, resulting in decreased invasiveness and AR transcriptional activity, and induced sensitivity to androgen withdrawal in hormone-refractory cells.The data presented in this study indicate that in prostate cancer, metastasis correlates with cytoplasmic localization of FlnA and may be prevented by cleavage and subsequent nuclear translocation of this protein.

Dataset Information

Cytoplasmic versus nuclear THR alpha expression determines survival of ovarian cancer patients.

Purpose

Methods

Results

Conclusion

Publications

Cytoplasmic versus nuclear THR alpha expression determines survival of ovarian cancer patients.

Similar Datasets

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