Dataset Information

Neovascular PSMA expression is a common feature in malignant neoplasms of the thyroid.

ABSTRACT:

Aim

PSMA (prostate-specific membrane antigen) is physiologically expressed in normal prostate tissue and over expressed in prostate cancer cells, therefore constituting a potential target for antibody-based radioligand therapy. Very recent imaging findings reported PSMA-PET/CT uptake in various thyroid lesions. We were therefore encouraged to systematically analyse PSMA expression in different benign and malignant thyroid lesions.

Methods

Immunohistochemistry was used to detect PSMA expression in 101 thyroid lesions, while neovasculature was identified by CD34 immunostaining.

Results

PSMA expression in the neovasculature was significantly more frequent in malignant tumors (36/63; 57.1%) compared to benign diseases (5/38; 13.2%; p = 0.0001). In addition, PSMA expression levels in the neovasculature of poorly and undifferentiated thyroid cancers were significantly higher compared to differentiated thyroid tumors (p = 0.021). However, one case with a strong expression in follicular adenoma was identified.

Conclusions

We conclude that neovascular PSMA expression is common in thyroid cancer but may also rarely be found in benign thyroid diseases, such as follicular adenoma. High expression in the tumor-associated neovasculature is predominantly found in poorly differentiated and undifferentiated (anaplastic) thyroid cancer. This knowledge is highly relevant when interpreting PSMA/PET-CT scans from patients with prostate cancer. In addition, our findings might provide a rationale for further evaluation of PSMA-targeted anti-neovascular or radioligand therapy in metastatic dedifferentiated thyroid cancer.

SUBMITTER: Heitkotter B

PROVIDER: S-EPMC5839407 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Publications

Neovascular PSMA expression is a common feature in malignant neoplasms of the thyroid.

Heitkötter Birthe B Steinestel Konrad K Trautmann Marcel M Grünewald Inga I Barth Peter P Gevensleben Heidrun H Bögemann Martin M Wardelmann Eva E Hartmann Wolfgang W Rahbar Kambiz K Huss Sebastian S

Oncotarget 20180104 11

<h4>Aim</h4>PSMA (prostate-specific membrane antigen) is physiologically expressed in normal prostate tissue and over expressed in prostate cancer cells, therefore constituting a potential target for antibody-based radioligand therapy. Very recent imaging findings reported PSMA-PET/CT uptake in various thyroid lesions. We were therefore encouraged to systematically analyse PSMA expression in different benign and malignant thyroid lesions.<h4>Methods</h4>Immunohistochemistry was used to detect PS ...[more]

PMID: 29515776

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Project description:BACKGROUND:Prostate-specific membrane antigen (PSMA) is overexpressed on the endothelial cells of tumor neo-vessels of several solid malignancies, including differentiated thyroid cancer (DTC). We aimed to test the potential role of PSMA as a biomarker for DTC aggressiveness and outcome prediction. We retrospectively screened all patients who underwent thyroidectomy between 1 January 2010 and 31 December 2017 in our institution. Applying the inclusion (histological diagnosis of thyroid cancer and tissue availability) and exclusion criteria (no clinical or follow-up data or diagnosis of medullary thyroid cancer), a cohort of 59 patients was selected. The monoclonal mouse anti-human PSMA antibody was used to stain tissue sections. A 3-point scale was used to score PSMA positivity: 0-5% expression was considered as negative (score 0), 6-50% as moderately positive (score 1), and 51-100% as highly positive (score 2). A cumulative score (0-10%, 11-79%, and 80-100%) was also explored. Univariate and multivariate logistic regression analyses were performed to predict the presence of distant metastases, chosen as endpoint of aggressiveness. The area under the curve (AUC) was calculated. Cox models were built to predict patient outcome in terms of recurrence, iodine refractoriness, and status at last follow-up, which were calculated using the Kaplan-Meier failure function. RESULTS:At immunostaining, 12, 25, and 22 patients had scores of 0, 1, and 2, respectively. According to the cumulative score, PSMA expression was ??10% in 17 cases, 11-79% in 31 cases, and ??80% in 11 cases. At multivariate analysis, age, sex, histotype, vascular invasion, T and N parameters, and PSMA positivity were significant predictors of distant metastases. The AUC was 0.92. Recurrence or progression occurred in 19/59 patients. Twelve patients developed radioiodine (RAI) refractoriness, after a median time of 17?months (range 2-32). One patient died of DTC; 46 of the 58 patients alive at last follow-up were disease free. Median DFS was 23?months (range 3-82). The final multivariate model to predict RAI refractoriness included as covariates the stage, high PSMA expression (??80%), and the interaction between moderate PSMA expression (11-79%) and stage. CONCLUSIONS:PSMA, a marker of neovasculature formation expressed by DTC, contributes in the prediction of tumor aggressiveness and patient outcome.

Dataset Information

Neovascular PSMA expression is a common feature in malignant neoplasms of the thyroid.

Aim

Methods

Results

Conclusions

Publications

Neovascular PSMA expression is a common feature in malignant neoplasms of the thyroid.

Similar Datasets

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