Backgrounds: Folate Hydrolase-1 (FOLH1; PSMA) is a type II transmembrane protein, luminally expressed by solid tumour neo-vasculature. Monoclonal antibody (mAb), J591, is a vehicle for mAb-based brachytherapy in FOLH1+ cancers. Brachytherapy is a form of radiotherapy that involves placing a radioactive material a short distance from the target tissue (e.g., on the skin or internally); brachytherapy is commonly accomplished with the use of catheters, needles, metal seeds and antibody or small peptide conjugates. Herein, FOLH1 expression in primary (p) and metastatic (m) Merkel cell carcinoma (MCC) is characterized to determine its targeting potential for J591-brachytherapy. Materials & Methods: Paraffin sections from pMCC and mMCC were evaluated by immunohistochemistry for FOLH1. Monte Carlo simulation was performed using the physical properties of conjugated radioisotope lutetium-177. Kaplan-Meier survival curves were calculated based on patient outcome data and FOLH1 expression. Results: Eighty-one MCC tumours were evaluated. 67% (54/81) of all cases, 77% (24/31) pMCC and 60% (30/50) mMCC tumours were FOLH1+. Monte Carlo simulation showed highly localized ionizing tracks of electrons emitted from the targeted neo-vessel. 42% (34/81) of patients with FOLH1+/- MCC had available survival data f or analysis. No significant differences in our limited data set were detected based on FOLH1 status (p = 0.4718; p = 0.6470), staining intensity score (p = 0.6966; p = 0.9841) or by grouping staining intensity scores (- and + vs. ++, +++, +++) (p = 0.8022; p = 0.8496) for MCC-specific survival or recurrence free survival, respectively. Conclusions: We report the first evidence of prevalent FOLH1 expression within MCC-associated neo-vessels, in 60-77% of patients in a large MCC cohort. Given this data, and the need for alternatives to immune therapies it is appropriate to explore the safety and efficacy o f FOLH1-targeted brachytherapy for MCC.
- Publikační typ
- časopisecké články MeSH
We report a case of a 65-year-old man examined for hematuria and neurologic symptoms. Radiologically a tumour of the kidney was suspected, with metastatic involvement of the brain and both lungs. The urologists then performed a cytoreductive nephrectomy.In histopathological examination of the nephrectomy specimen a clear cell renal cell carcinoma (clear cell RCC) was found. However, an additional focus of a high-grade adenocarcinoma was discovered that turned out to be a metastasis of a poor differentiated lung adenocarcinoma. This diagnosis was supported by positive TTF1 and napsin-A as well as good clinical correlations.The article summarizes the differential diagnostic considerations of poor differentiated adenocarcinoma of the kidney, aimed at gross and microscopic morphology, immunohistochemistry and clinical-pathological correlation. A review of literature about a tumour-in-tumour metastasis is included.
- MeSH
- adenokarcinom * MeSH
- karcinom z renálních buněk * MeSH
- lidé MeSH
- mnohočetné primární nádory * MeSH
- nádory ledvin * MeSH
- nefrektomie MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- MeSH
- angiolymfoidní hyperplazie s eozinofilií chirurgie patologie MeSH
- diferenciální diagnóza MeSH
- lidé MeSH
- nemoci orbity chirurgie patologie MeSH
- nemoci slzného ústrojí diagnóza chirurgie patologie MeSH
- pooperační komplikace diagnóza chirurgie patologie MeSH
- recidiva MeSH
- reoperace MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- kazuistiky MeSH
- MeSH
- demence etiologie MeSH
- lidé MeSH
- nádory mozku diagnóza komplikace MeSH
- paréza etiologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- MeSH
- alkoholismus komplikace terapie MeSH
- duševní poruchy etiologie MeSH
- hospitalizace MeSH
- lidé MeSH
- longitudinální studie MeSH
- neurologické manifestace etiologie MeSH
- odvykací prostředky alkoholu škodlivé účinky MeSH
- vnitřní lékařství MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- srovnávací studie MeSH
- MeSH
- karcinoid MeSH
- lidé středního věku MeSH
- lidé MeSH
- metastázy nádorů MeSH
- střevní nádory MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
