Altered TP53, CDKN2A, ATM, EPHA7, POT1, CHEK1, GRIN2A, and EGFR Predict Shorter Survival in Penile Squamous Cell Carcinoma
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064173%3A_____%2F25%3A43927807" target="_blank" >RIV/00064173:_____/25:43927807 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/25:10489013 RIV/00216208:11120/25:43927807 RIV/00064165:_____/25:10489013
Result on the web
<a href="https://doi.org/10.1016/j.modpat.2024.100689" target="_blank" >https://doi.org/10.1016/j.modpat.2024.100689</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.modpat.2024.100689" target="_blank" >10.1016/j.modpat.2024.100689</a>
Alternative languages
Result language
angličtina
Original language name
Altered TP53, CDKN2A, ATM, EPHA7, POT1, CHEK1, GRIN2A, and EGFR Predict Shorter Survival in Penile Squamous Cell Carcinoma
Original language description
Penile squamous cell carcinoma (pSCC) represents an uncommon malignancy characterized by stagnant mortality, psychosexual distress, and a highly variable prognosis. Currently, the WHO distinguishes between human papillomavirus (HPV) related and HPV independent pSCC. Recently, there has been an evolving line of research documenting the enrichment of HPV-independent pSCC with a high tumor mutational burden (TMB) and programmed death ligand-1 (PD-L1) expression, as well as clusters of genes associated with HPV status. In this study, we conducted comprehensive next-generation sequencing (NGS) DNA profiling of 146 pSCC samples using a panel consisting of 355 genes associated with tumors. This profiling was correlated with immunohistochemical markers and prognostic clinical data. A survival analysis of recurrent genomic events (found in >=10 cases) was performed. TP53, CDKN2A, ATM, EPHA7, POT1, CHEK1, GRIN2A, and EGFR alterations were associated with significantly shortened overall survival (OS) in univariate and multivariate analysis. HPV positivity, diagnosed through both p16 immunohistochemistry and HPV DNA analysis, displayed no impact on survival but was associated with high grade, lymphatic invasion, PD-L1 negativity/weak expression, and low TMB. FAT1, TP53, CDKN2A, CASP8, and HRAS were more often mutated in HPV-independent pSCC. In contrast, HPV associated pSCCs were enriched by EPHA7, ATM, GRIN2A and CHEK1 mutations. PIK3CA, FAT1, FBXW7, and KMT2D mutations were associated with high TMB. NOTCH1, TP53, CDKN2A, POT1, KMT2D, ATM, CHEK1, EPHA3, and EGFR alterations were related with adverse clinical-pathological signs such as advanced stage, high tumor budding, and lymphovascular invasion. We detected 160 alterations with potential treatment implications, with 21.2% of samples showing alterations in the homologous recombination pathway. To the best of our knowledge, this study describes the largest cohort of pSCC with complex molecular-pathological, clinical, and prognostic analysis correlating with prognosis.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30109 - Pathology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Modern Pathology
ISSN
0893-3952
e-ISSN
1530-0285
Volume of the periodical
38
Issue of the periodical within the volume
4
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
100689
UT code for WoS article
001399563900001
EID of the result in the Scopus database
2-s2.0-85214909385