Altered TP53, CDKN2A, ATM, EPHA7, POT1, CHEK1, GRIN2A, and EGFR Predict Shorter Survival in Penile Squamous Cell Carcinoma

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/00216208:11110/25:10489013 RIV/00216208:11120/25:43927807 RIV/00064165:_____/25:10489013

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Altered TP53, CDKN2A, ATM, EPHA7, POT1, CHEK1, GRIN2A, and EGFR Predict Shorter Survival in Penile Squamous Cell Carcinoma

Popis výsledku v původním jazyce

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 &gt;=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.

Název v anglickém jazyce

Altered TP53, CDKN2A, ATM, EPHA7, POT1, CHEK1, GRIN2A, and EGFR Predict Shorter Survival in Penile Squamous Cell Carcinoma

Popis výsledku anglicky

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 &gt;=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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30109 - Pathology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Modern Pathology

ISSN

0893-3952

e-ISSN

1530-0285

Svazek periodika

38

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

100689

Kód UT WoS článku

001399563900001

EID výsledku v databázi Scopus

2-s2.0-85214909385