Prostate‐specific membrane antigen expression in melanoma metastases

Snow, Hayden; Hazell, Stephen; Francis, Nicholas; Mohammed, Kabir; O'Neill, Stéphanie; Davies, Emma; Mansfield, David; Messiou, Christina; Hujairi, Nabil; Nicol, David; Harrington, Kevin; Smith, Myles

doi:10.1111/cup.13774

Cited by 9 publications

(6 citation statements)

References 33 publications

(45 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Tissue expression of CCR6 and its ligand CCL20 (MIP-3a) were identified as progression predictors in primary melanoma patients [11]. Prostate-specific membrane antigen (PSMA) was identified by immunohistochemistry analysis as a good marker of metastatic melanoma, in 41 Stage III/IV melanoma human specimens [12]. The ROC analysis measured an AUC = 0.82, i.e., a good performance but not good enough to allow its clinical application as a melanoma marker.…”

Section: Introductionmentioning

confidence: 99%

Investigating Serum and Tissue Expression Identified a Cytokine/Chemokine Signature as a Highly Effective Melanoma Marker

Cesati

Scatozza

D’Arcangelo

et al. 2020

Cancers

View full text Add to dashboard Cite

The identification of reliable and quantitative melanoma biomarkers may help an early diagnosis and may directly affect melanoma mortality and morbidity. The aim of the present study was to identify effective biomarkers by investigating the expression of 27 cytokines/chemokines in melanoma compared to healthy controls, both in serum and in tissue samples. Serum samples were from 232 patients recruited at the IDI-IRCCS hospital. Expression was quantified by xMAP technology, on 27 cytokines/chemokines, compared to the control sera. RNA expression data of the same 27 molecules were obtained from 511 melanoma- and healthy-tissue samples, from the GENT2 database. Statistical analysis involved a 3-step approach: analysis of the single-molecules by Mann–Whitney analysis; analysis of paired-molecules by Pearson correlation; and profile analysis by the machine learning algorithm Support Vector Machine (SVM). Single-molecule analysis of serum expression identified IL-1b, IL-6, IP-10, PDGF-BB, and RANTES differently expressed in melanoma (p < 0.05). Expression of IL-8, GM-CSF, MCP-1, and TNF-α was found to be significantly correlated with Breslow thickness. Eotaxin and MCP-1 were found differentially expressed in male vs. female patients. Tissue expression analysis identified very effective marker/predictor genes, namely, IL-1Ra, IL-7, MIP-1a, and MIP-1b, with individual AUC values of 0.88, 0.86, 0.93, 0.87, respectively. SVM analysis of the tissue expression data identified the combination of these four molecules as the most effective signature to discriminate melanoma patients (AUC = 0.98). Validation, using the GEPIA2 database on an additional 1019 independent samples, fully confirmed these observations. The present study demonstrates, for the first time, that the IL-1Ra, IL-7, MIP-1a, and MIP-1b gene signature discriminates melanoma from control tissues with extremely high efficacy. We therefore propose this 4-molecule combination as an effective melanoma marker.

show abstract

Section: Introductionmentioning

confidence: 99%

Investigating Serum and Tissue Expression Identified a Cytokine/Chemokine Signature as a Highly Effective Melanoma Marker

Cesati

Scatozza

D’Arcangelo

et al. 2020

Cancers

View full text Add to dashboard Cite

show abstract

“…Skin uptake in multiple locations was noticed in two patients with no specific corresponding abnormality. Uptake of [ 18 F]PSMA-1007 was previously reported in several skin conditions including neurofibromatosis, melanoma and angiolipoma, mostly associated with PSMA expression in endothelial capillaries (22)(23)(24).…”

Section: Discussionmentioning

confidence: 94%

False Positive Findings of [18F]PSMA-1007 PET/CT in Patients After Radical Prostatectomy with Undetectable Serum PSA Levels

et al. 2022

View full text Add to dashboard Cite

BackgroundPET-CT using prostate-specific membrane antigen (PSMA)-targeting radiopharmaceuticals labeled with 68Ga or 18F has emerged as the most sensitive staging tool in prostate cancer (PC). Nonetheless, the occurrence of false positive (FP) findings presents a major concern of this approach. In this prospective study, we investigated the frequency and pattern of false-positive findings of [18F]PSMA-1007 PET/CT in patients after radical prostatectomy with undetectable serum PSA levels. Any discrete non-physiological accumulation of [18F]PSMA-1007 in this population is by definition FP.MethodsSeventeen men after radical prostatectomy, whose serum PSA levels were <0.05 ng/mL at 2–24 months after surgery were prospectively recruited. PET/CT was acquired at both 1 and 2 h after injection of [18F]PSMA-1007.FindingsThree studies (18%) were interpreted as completely normal. Thirty-five foci of “non-physiological” uptake were observed in the remaining 14 (82%) patients, including a single skeletal focus in four patients, multiple skeletal foci in five patients and soft tissue uptake in eight, including in a desmoid tumor and in pelvic lymphocele. The SUVmax of all lesions was in the range of 1–7, except for the desmoid tumor which measured 12.7. All foci were visible in both the 1- and the 2 h studies, presenting a minor (<10%), statistically insignificant increase of SUVmax during this time-interval.InterpretationFP [18F]PSMA-1007-avid foci are found in about 80% of patients with undetectable serum PSA levels. Thus, focal uptake of [18F]PSMA-1007 outside its physiological distribution is not a categorical sign of metastasis and can arise from non-specific uptake of the ligand. The interpretation of [18F]PSMA-1007 PET/CT studies should always consider the clinical context, and lesions with SUVmax < 7 are suspicious for FP.

show abstract

“…Finally, PSMA expression on the endothelium of tumoral vessels has been detected in many other different tumors, including more common histotypes, such as oral squamous cell carcinomas [ 104 , 105 ] and melanomas [ 106 ], and relatively rare neoplasms, such as endolymphatic sac tumors [ 107 ].…”

Section: Other Cancersmentioning

confidence: 99%

PSMA Expression in Solid Tumors beyond the Prostate Gland: Ready for Theranostic Applications?

Lauri¹,

Chiurchioni²,

Russo³

et al. 2022

JCM

View full text Add to dashboard Cite

In the past decades, the expanding use of prostate-specific membrane antigen (PSMA) imaging for prostate cancer has led to the incidental detection of a lot of extra-prostatic malignancies showing an increased uptake of PSMA. Due to these incidental findings, the increasing amount of immunohistochemistry studies and the deeper knowledge of the mechanisms of expression of this antigen, it is now clear that “PSMA” is a misnomer, since it is not specific to the prostate gland. Nevertheless, this lack of specificity could represent an interesting opportunity to bring new insights on the biology of PSMA and its sites of expression to image and treat new conditions, particularly several cancers. In this review, we will describe the main extra-prostatic cancers that exhibit PSMA expression and that can be studied with PSMA-based positron emission tomography–computed tomography (PET/CT) as an additional or alternative tool to conventional imaging. In particular, we will focus on cancers in which a radioligand therapy with 177lutetium has been attempted, aiming to provide an overview of the possible future theragnostic applications of PSMA.

show abstract

Prostate‐specific membrane antigen expression in melanoma metastases

Cited by 9 publications

References 33 publications

Investigating Serum and Tissue Expression Identified a Cytokine/Chemokine Signature as a Highly Effective Melanoma Marker

Investigating Serum and Tissue Expression Identified a Cytokine/Chemokine Signature as a Highly Effective Melanoma Marker

False Positive Findings of [18F]PSMA-1007 PET/CT in Patients After Radical Prostatectomy with Undetectable Serum PSA Levels

PSMA Expression in Solid Tumors beyond the Prostate Gland: Ready for Theranostic Applications?

Contact Info

Product

Resources

About