The Mixed Epithelial and Stroma Tumor (MEST) of the kidney is an uncommon type of neoplasm that displays a unique biphasic pattern consisting of both epithelial and mesenchymal elements. At Protheragen, we use our vast industry experience and deep expertise as a biological specialist company to provide fully integrated MEST diagnostics services alongside preclinical therapeutics development services.
Overview of Mixed Epithelial and Stroma Tumor (MEST)
Mixed Epithelial and Stroma Tumor (MEST) is a distinct, rare renal tumor with two phases that features both an epithelial tumor and a stromal (mesenchymal) component. It was first described by Michal and Syrucek in 1998. MEST comprises roughly 0.2% of all renal tumors and has a striking female predominance (male to female ratio 1:10). The female predominance in the description was noted almost twenty five years ago, where now, the age cystic or tubulopapillary lesions lined with cuboidal to hobnail epithelium make up the majority, some of these do exhibit ovarian like stromaand frequently demonstrate estrogen receptor (ER) and progesterone receptor (PR) positive qualities. While classed as benign generally, there have been cases reported of malignant transformation into sarcomatoid or rhabdoid cancer.
Fig.1 MEST family pedigree and imaging. (Vocke C. D.,
et al., 2019)
Pathogenesis of Mixed Epithelial and Stroma Tumor (MEST)
The etiology of MEST remains incompletely understood, but several key mechanisms have been implicated:
- Hormonal Influence: ER/PR positivity in the stromal component and the tumor's predilection for perimenopausal/postmenopausal women suggest a role for hormonal imbalance. Long-term estrogen exposure or hormone replacement therapy may contribute to tumorigenesis.
- Genetic Predisposition: Germline mutations in CDC73 (encoding parafibromin) have been identified in familial cases of bilateral/multifocal MEST. Somatic copy-neutral loss of heterozygosity (LOH) at the CDC73 locus further supports a tumor suppressor mechanism.
- Müllerian Remnant Hypothesis: The ovarian-like stroma suggests derivation from misplaced Müllerian remnants during embryogenesis, aligning with the tumor's frequent association with uterine fibroids and endometrial pathology.
Diagnostics Development for Mixed Epithelial and Stroma Tumor (MEST)
Imaging Modalities
Contrast-Enhanced CT/MRI: Reveals solid-cystic renal masses with septations, often hypermetabolic on FDG-PET. However, imaging lacks specificity for definitive diagnosis.
FDG-PET/CT: Useful for detecting hypermetabolic activity in primary tumors and lymph nodes, aiding in staging and recurrence monitoring.
Histopathological and Immunohistochemical Analysis
Core Biopsy/FNA: Limited utility due to frequent acellular samples; definitive diagnosis requires surgical resection.
IHC Panel: Stromal positivity for ER, PR, desmin, and smooth muscle actin; epithelial positivity for cytokeratins (AE1/3) and PAX-8. Negative stains for HMB-45 and Melan-A help exclude melanocytic tumors.
Molecular Diagnostics
CDC73 Sequencing: CDC73 sequencing is a highly recommended molecular diagnostic approach, particularly in specific clinical scenarios. Recommended for bilateral/multifocal cases or family history to identify germline mutations and guide surveillance.
LOH Analysis: Confirms biallelic CDC73 inactivation in tumors, supporting tumor suppressor biology.
Therapeutics Development for Mixed Epithelial and Stroma Tumor (MEST)
- Targeted Therapies: Although no specific targeted therapies are currently approved for MEST, ongoing research is exploring the potential of hormonal therapies, given the tumor's hormonal sensitivity. Anti-estrogen and anti-progesterone agents may be considered in future therapeutic strategies.
- Immunotherapy: Immunotherapy, including immune checkpoint inhibitors, is an emerging area of interest in renal neoplasms. While there is limited data on the efficacy of immunotherapy in MEST specifically, its role in other renal tumors suggests potential for future exploration.
Table 1. Therapeutics of Mixed Epithelial and Stroma Tumor (MEST).
| Therapeutics |
Target |
Description |
Stage |
| Doxorubicin-based Regimens |
DNA/Topoisomerase II |
Anecdotal use for sarcomatoid variants of MEST, but no standardized protocols or efficacy data. |
Approved |
| Radiation Therapy |
DNA Damage |
Not routinely used; may be considered for palliation in metastatic cases, but no documented outcomes. |
Approved |
| Hormonal Modulation |
Estrogen/Progesterone Receptors (ER/PR) |
Theoretical use of anti-estrogens (e.g., tamoxifen) for ER/PR-positive tumors, but no clinical data or trials cited. |
Preclinical |
| Targeted Therapy |
CDC73/HRPT2 |
Preclinical exploration of PARP inhibitors or Wnt/β-catenin pathway modulators due to CDC73 loss-of-function mutations. |
Preclinical |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen offers a comprehensive suite of services dedicated to the diagnostics and therapeutics development of MEST. Our services encompass imaging-based diagnostics, molecular and genetic testing, histopathological analysis, and the development of novel therapeutic strategies.
Disease Models
- CDC73 Knockout Mouse
- ER/PR Overexpression Models
- MEST-PDX in NSG Mice
- Tail Vein Metastasis Models
- Canine Spontaneous MEST Models
Protheragen provides tailored solutions to meet the unique needs of our clients. Our customized services include biomarker discovery and companion diagnostics development. We work closely with our partners to design and execute studies that address specific research questions and preclinical challenges. If you are interested in our services, please feel free to contact us.
References
- Vocke, Cathy D., et al. "CDC73 germline mutation in a family with mixed epithelial and stromal tumors." Urology 124 (2019): 91-97.
- Dan, Chitramalya, et al. "Mixed epithelial stromal tumor of the kidney with a mesenteric lymph node: A case report and literature review." Cureus 15.9 (2023): e46058.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
