Mucinous Tubular and Spindle Cell Carcinoma (MTSCC) is a precisely definable renal cell carcinoma subtype with complex histologic criteria and a multi-tiered grade continuum, posing diagnostic challenges and therapeutic complexities. At Protheragen, we provide full-spectrum diagnostic and therapeutic development services pertaining especially to MTSCC. Our offerings span several preclinical research activities, including target identification, target validation, drug discovery as well and preclinical testing.
Overview of Mucinous Tubular and Spindle Cell Carcinoma (MTSCC)
Mucinous Tubular and Spindle Cell Carcinoma (MTSCC) is a rare form of renal cell carcinoma (RCC) that has recently attracted considerable interest in oncology circles owing to its unusual histopathological characteristics and behavior. As described in the 2004 World Health Organization (WHO) tumor classification, they recognized MTSCC as distinct based on the composition of its mucinous stroma, which contains cuboidal cells that form tubules along with spindle cells. This unusual renal neoplasm occurs primarily in middle-aged adults, occurring over a wide age span, with females disproportionately affected more than males. Tumors typically present are typically found incidentally during imaging studies of the abdomen performed for other reasons.
Fig.1 Case of CT scan, nephrectomy specimen, and histopathological analysis of MTSCC. (Nathany S.,
et al., 2020)
Pathogenesis of Mucinous Tubular and Spindle Cell Carcinoma (MTSCC)
The exact pathogenic mechanisms underlying MTSCC remain largely unknown, but several hypotheses have been proposed. Initially, it was thought that MTSCC might originate from the cells of the loop of Henle or collecting duct epithelium. However, accumulating evidence suggests a proximal nephron origin, particularly given the uniform expression of markers such as CK7 and AMACR, which are more commonly associated with papillary RCC. Genomic investigations have revealed multiple chromosomal numerical aberrations in MTSCC, including losses and gains of chromosomes commonly seen in other RCC subtypes, yet MTSCC remains genetically distinct from papillary RCC. These findings suggest that MTSCC may arise from a distinct cell lineage within the kidney, potentially influenced by genetic alterations that drive its unique histological phenotype.
Diagnostics Development for Mucinous Tubular and Spindle Cell Carcinoma (MTSCC)
Immunohistochemistry (IHC)
IHC is instrumental in the diagnosis of MTSCC and aids in differentiating it from other subtypes of RCC. The neoplastic cells in MTSCC uniformly express PAX2/8, low molecular weight cytokeratin (CK7, CK8/18, CK19), EMA, AMACR, and E-cadherin. Expression of vimentin and high molecular weight cytokeratin 34BE12 is variable; CD10 and CD15 are negative in most cases but may be positive. Devising specific IHC diagnostic panels for MTSCC may improve accuracy in the differentiation of spiral cell predominance or scant mucin poses diagnostic challenges.
Molecular Genetic Testing
The genetic characterization of MTSCC has been advanced by molecular testing such as NGS and CGH. Studies identified recurrent alterations in the Hippo pathway, low mutational burden, and chromosomal loss to be distinct features of MTSCC at the molecular level. These insights contribute towards better differential diagnosis of MTSCC while also enabling precision therapeutic options. For example, mutations on the NF2 gene, a constituent of the Hippo pathway, have been noted with high frequency in MTSCC, which indicates potential mutations that could be therapeutically targeted.
Therapeutics Development for Mucinous Tubular and Spindle Cell Carcinoma (MTSCC)
- Targeted Therapy
Considering the molecular changes seen in MTSCC, some specific targeted therapies are being developed. For instance, NF2 mutation identification in MTSCC may utilize inhibitors of the Hippo pathway and downstream effector modification as potential therapeutic options. Moreover, because MTSCC has some genetic affinities with papillary RCC, some antibodies targeting the VEGF pathway, like sunitinib, have been effective in certain cases.
- Immunotherapy
The advent of immunotherapy and, more specifically, its checkpoint inhibitors, has transformed the therapeutic of several solid tumors, including RCC. The effectiveness of immunotherapy for MTSCC, however, remains more ambiguous. A small number of case reports detail the administration of nivolumab in metastatic MTSCC and report mixed responses; some patients exhibit stabilization or partial response, while others have rapid progression. Such variability emphasizes the necessity to further study predictive markers that respond to immunotherapy in MTSCC.
Table 1. Therapeutics of Mucinous Tubular and Spindle Cell Carcinoma (MTSCC).
| Therapeutics |
Drug Name |
Target |
Description |
Stage |
| Systemic Therapy |
Sunitinib |
VEGF |
Tyrosine kinase inhibitors targeting vascular endothelial growth factor (VEGF) to inhibit tumor angiogenesis. |
Approved |
| Systemic Therapy |
Pazopanib |
VEGF |
Tyrosine kinase inhibitors targeting VEGF to inhibit tumor angiogenesis. |
Approved |
| Systemic Therapy |
Sorafenib |
VEGF |
Tyrosine kinase inhibitors targeting VEGF to inhibit tumor angiogenesis. |
Approved |
| Immunotherapy |
Nivolumab |
PD-1 |
Immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) to enhance the immune response against cancer cells. |
Approved |
| Targeted Therapy |
Bevacizumab |
VEGF |
Monoclonal antibody targeting VEGF to inhibit tumor angiogenesis. |
Approved |
| Chemotherapy |
Gemcitabine |
DNA |
Inhibits DNA synthesis, leading to cell cycle arrest and apoptosis in cancer cells. |
Approved |
| Chemotherapy |
Capecitabine |
DNA |
Prodrug converted to 5-FU in the body, inhibiting DNA synthesis and causing cell cycle arrest and apoptosis. |
Approved |
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
At Protheragen, we are concerned with every aspect of the Mucinous Tubular and Spindle Cell Carcinoma (MTTSCC) tumor's diagnostic and therapeutic development spectrum. In relation to biomarker discovery, diagnostics development, target validation, therapeutic candidate progression and transitioning into preclinical to clinical stages, our comprehensive services are tailored to facilitate your research goals.
- Genetically Engineered Mouse Models (GEMMs)
- Xenograft Models
- Spontaneous Tumor Models
- Chemically Induced Models
- Humanized Models
Protheragen's services range from the preparation of a diagnostic IHC panel specific to your research questions as well as devising a preclinical study for evaluation of therapeutic agents. With us at Protheragen, you would always receive customized attention. If you are interested in our services, please feel free to contact us.
References
- Nathany, Shrinidhi, and Vidya Monappa. "Mucinous tubular and spindle cell carcinoma: A review of histopathology and clinical and prognostic implications." Archives of pathology & laboratory medicine 144.1 (2020): 115-118.
- Kenney, Patrick A., et al. "Mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney: a detailed study of radiological, pathological and clinical outcomes." BJU international 116.1 (2015): 85-92.
- Ged, Yasser, et al. "Mucinous tubular and spindle-cell carcinoma of the kidney: clinical features, genomic profiles, and treatment outcomes." Clinical genitourinary cancer 17.4 (2019): 268-274.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
