Elevated Microsatellite Alterations at Selected Tetranucleotide Repeats (EMAST) in Penile Squamous Cell Carcinoma-No Evidence for a Role in Carcinogenesis.

Fiegl A, Wendler O, Giedl J, Gaisa NT, Richter G, Campean V, Burger M, Simmer F, Nagtegaal I, Wullich B, Bertz S, Hartmann A, Stöhr R (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Book Volume: 31

Pages Range: 5752-5761

Journal Issue: 10

DOI: 10.3390/curroncol31100427

Abstract

Penile squamous cell carcinoma (pSCC) is a rare malignancy with a global incidence ranging from 0.1 to 0.7 per 100,000 males. Prognosis is generally favorable for localized tumors, but metastatic pSCC remains challenging, with low survival rates. The role of novel biomarkers, such as tumor mutational burden (TMB) and microsatellite instability (MSI), in predicting the response to immune checkpoint inhibitors (ICIs) has been investigated in various cancers. However, MSI has not been observed in pSCC, limiting immunotherapy options for this patient subgroup. Elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) are a distinct form of genomic instability associated with deficient MSH3 expression, which has been proposed as a potential biomarker in several cancers. This study investigates EMAST and MSH3 expression in a cohort of 78 pSCC cases using PCR, fragment analysis and immunohistochemistry. For the detection of EMAST, the stability of five microsatellite markers (D9S242, D20S82, MYCL1, D8S321 and D20S85) was analyzed. None of the cases showed an instability. As for MSH3 immunohistochemistry, all analyzable cases showed retained MSH3 expression. These results strongly suggest that neither EMAST nor MSH3 deficiency is involved in the carcinogenesis of pSCC and do not represent reliable predictive biomarkers in this entity. Furthermore, these findings are in full agreement with our previous study showing a very low frequency of MSI and further support the thesis that EMAST and MSI are strongly interconnected forms of genomic instability. Further research is needed to explore novel therapeutic targets and predictive biomarkers for immunotherapy in this patient population.

Authors with CRIS profile

Additional Organisation(s)

Involved external institutions

Universitätsklinikum Ulm Germany (DE) Pathologie Ansbach Germany (DE) Radboud University Nijmegen Medical Centre / Radboudumc of voluit Radboud Universitair Medisch Centrum (UMC) Netherlands (NL) Universität Regensburg Germany (DE)

How to cite

APA:

Fiegl, A., Wendler, O., Giedl, J., Gaisa, N.T., Richter, G., Campean, V.,... Stöhr, R. (2024). Elevated Microsatellite Alterations at Selected Tetranucleotide Repeats (EMAST) in Penile Squamous Cell Carcinoma-No Evidence for a Role in Carcinogenesis. Current Oncology, 31(10), 5752-5761. https://doi.org/10.3390/curroncol31100427

MLA:

Fiegl, August, et al. "Elevated Microsatellite Alterations at Selected Tetranucleotide Repeats (EMAST) in Penile Squamous Cell Carcinoma-No Evidence for a Role in Carcinogenesis." Current Oncology 31.10 (2024): 5752-5761.

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