Dataset Information

Prostate-specific membrane antigen (PSMA) expression in adenoid cystic carcinoma of the head and neck.

ABSTRACT:

Background

Treatment options for advanced head and neck adenoid cystic carcinoma (AdCC) are limited. Prostate-Specific Membrane Antigen (PSMA), a transmembrane protein that is known for its use in diagnostics and targeted therapy in prostate cancer, is also expressed by AdCC. This study aimed to analyse PSMA expression in a large cohort of primary, recurrent and metastasized AdCC of the head and neck.

Methods

One hundred ten consecutive patients with histologically confirmed AdCC in the period 1990-2017 were included. An analysis was made of clinical details, revised pathology and semiquantitative immunohistochemical expression of PSMA on tissue microarray and whole slides. Associations of PSMA expression with clinicopathological parameters were explored and survival was analysed by multivariate Cox-proportional Hazard analysis.

Results

PSMA expression was present in 94% of the 110 primary tumours, with a median of 31% positive cells (IQR 15-60%). Primary tumours (n =?18) that recurred (n =?15) and/or had metastases (n =?10) demonstrated 40, 60 and 23% expression respectively. Expression was not independently related to increased pathological stage, tumour grade, and the occurrence of locoregional recurrence or metastasis. After dichotomization, only primary tumour PSMA expression ?10% appeared to be associated with reduced 10-years recurrence-free survival (HR 3.0, 95% CI 1.1-8.5, p =?.04).

Conclusions

PSMA is highly expressed in primary, recurrent and metastatic AdCC of the salivary and seromucous glands. PSMA expression has no value in predicting clinical behaviour of AdCC although low expression may indicate a reduced recurrence-free survival. This study provides supporting results to consider using PSMA as target for imaging and therapy when other diagnostic and palliative treatment options fail.

SUBMITTER: Klein Nulent TJW

PROVIDER: S-EPMC7275445 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

Prostate-specific membrane antigen (PSMA) expression in adenoid cystic carcinoma of the head and neck.

Klein Nulent Thomas J W TJW Valstar Matthijs H MH Smit Laura A LA Smeele Ludwig E LE Zuithoff Nicolaas P A NPA de Keizer Bart B de Bree Remco R van Es Robert J J RJJ Willems Stefan M SM

BMC cancer 20200605 1

<h4>Background</h4>Treatment options for advanced head and neck adenoid cystic carcinoma (AdCC) are limited. Prostate-Specific Membrane Antigen (PSMA), a transmembrane protein that is known for its use in diagnostics and targeted therapy in prostate cancer, is also expressed by AdCC. This study aimed to analyse PSMA expression in a large cohort of primary, recurrent and metastasized AdCC of the head and neck.<h4>Methods</h4>One hundred ten consecutive patients with histologically confirmed AdCC ...[more]

PMID: 32503460

Similar Datasets

Project description:BackgroundPSMA expression in the prostate epithelium is controlled by a cis-element, PSMA enhancer (PSME). PSME contains multiple binding sites for Sox proteins, and in this study, we identified Sox7 protein as a negative regulator of PSMA expression through its interaction with PSME.MethodsThe statistical correlation between Sox7 and PSMA mRNA expression was evaluated using five prostate cancer studies from cBioportal. In vitro and in vivo interaction between Sox7 and PSME was evaluated by chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA), and luciferase reporter assay. Synthetic oligonucleotides were generated to define the sites in PSME that interact with Sox7 protein. Sox7 mutants were generated to identify the region of this protein required to regulate PSMA expression. Sox7 was also stably expressed in LNCaP/C4-2 and 22Rv1 cells to validate the regulation of PSMA expression by Sox7 in vivo.ResultsSox7 mRNA expression negatively correlated with PSMA/FOLH1 and PSMAL/FOLH1B mRNA expression in Broad/Cornell, TCGA and MSKCC studies, but not in two studies containing only metastatic prostate tumors. PC-3 cells mostly expressed the 48.5 KDa isoform 2 of Sox7, and the depletion of this isoform did not restore PSMA expression. Ectopic expression of canonical, wild-type Sox7 in C4-2 and 22Rv1 cells suppressed PSMA protein expression. ChIP assay revealed that canonical Sox7 protein preferentially interacts with PSME in vivo, and EMSA identified the SOX box sites #2 and #4 in PSME as required for its interaction. Sox7 was capable of directly binding to PSME and suppressed PSME-mediated transcription. The NLS regions of Sox7, but not its β-catenin interacting motif, are essential for this suppressing activity. Furthermore, restoration of wild-type Sox7 expression but not Sox7-NLS mutant in Sox7-null prostate cancer cell lines suppressed PSMA expression.ConclusionsThe inactivation of canonical Sox7 is responsible for the upregulated expression of PSMA in non-metastatic prostate cancer.

Dataset Information

Prostate-specific membrane antigen (PSMA) expression in adenoid cystic carcinoma of the head and neck.

Background

Methods

Results

Conclusions

Publications

Prostate-specific membrane antigen (PSMA) expression in adenoid cystic carcinoma of the head and neck.

Similar Datasets

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