High tumour mutational burden is associated with strong PD-L1 expression, HPV negativity, and worse survival in penile squamous cell carcinoma: an analysis of 165 cases

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064173%3A_____%2F24%3A43926512" target="_blank" >RIV/00064173:_____/24:43926512 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/24:10473596 RIV/00216208:11120/24:43926512 RIV/00064190:_____/24:10001235 RIV/00064165:_____/24:10473596

Výsledek na webu

<a href="https://doi.org/10.1016/j.pathol.2023.10.010" target="_blank" >https://doi.org/10.1016/j.pathol.2023.10.010</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.pathol.2023.10.010" target="_blank" >10.1016/j.pathol.2023.10.010</a>

Jazyk výsledku

angličtina

Název v původním jazyce

High tumour mutational burden is associated with strong PD-L1 expression, HPV negativity, and worse survival in penile squamous cell carcinoma: an analysis of 165 cases

Popis výsledku v původním jazyce

Penile squamous cell carcinoma (pSCC) is a rare tumour with a variable prognosis. More prognostic markers linked to mutational signatures and the tumour immune microenvironment are needed. A cohort made up of 165 invasive pSCC was retrospectively analysed using formalin-fixed, paraffin-embedded tumour tissue, focusing on tumour mutational burden (TMB), programmed death ligand 1 (PD-L1) expression, microsatellite instability (MSI), the number of tumour infiltrating lymphocytes (TILs) expressing cytotoxic T-lymphocyte-associated protein 4 (CTLA4), HPV status determined by p16 immunohistochemistry, and several traditional histopathological variables. High TMB (&gt;10 mut/Mb) was associated with high PD-L1 expression (TPS 50-100%), and HPV-negative status. High PD-L1 expression was linked to HPV negativity, a high number of intratumoural CTLA4+ cells, and brisk lymphocytic infiltrate. High TMB was a significant predictor of shorter overall survival (OS) in both univariate and multivariate analysis when using a median cut-off value of 4.3 mut/Mb, but not when using an arbitrary cut-off of 10 mut/Mb. Low CTLA4+ cell infiltration at the tumour invasion front was a marker of shorter OS and cancer-specific survival in both univariate and multivariate analysis. PD-L1 expression had no significant impact on prognosis. Only two cases were MSI high. The results support the hypothesis of two aetiological pathways in pSCC cancerogenesis: (1) SCC linked to HPV infection characterised by low TMB, less common PD-L1 expression, and a lower number of TILs; and (2) SCC linked to chronic inflammation leading to a high number of acquired mutations (high TMB), HPV negativity, increased neoantigen production (i.e., PD-L1), and high immune cell infiltration.

Název v anglickém jazyce

High tumour mutational burden is associated with strong PD-L1 expression, HPV negativity, and worse survival in penile squamous cell carcinoma: an analysis of 165 cases

Popis výsledku anglicky

Penile squamous cell carcinoma (pSCC) is a rare tumour with a variable prognosis. More prognostic markers linked to mutational signatures and the tumour immune microenvironment are needed. A cohort made up of 165 invasive pSCC was retrospectively analysed using formalin-fixed, paraffin-embedded tumour tissue, focusing on tumour mutational burden (TMB), programmed death ligand 1 (PD-L1) expression, microsatellite instability (MSI), the number of tumour infiltrating lymphocytes (TILs) expressing cytotoxic T-lymphocyte-associated protein 4 (CTLA4), HPV status determined by p16 immunohistochemistry, and several traditional histopathological variables. High TMB (&gt;10 mut/Mb) was associated with high PD-L1 expression (TPS 50-100%), and HPV-negative status. High PD-L1 expression was linked to HPV negativity, a high number of intratumoural CTLA4+ cells, and brisk lymphocytic infiltrate. High TMB was a significant predictor of shorter overall survival (OS) in both univariate and multivariate analysis when using a median cut-off value of 4.3 mut/Mb, but not when using an arbitrary cut-off of 10 mut/Mb. Low CTLA4+ cell infiltration at the tumour invasion front was a marker of shorter OS and cancer-specific survival in both univariate and multivariate analysis. PD-L1 expression had no significant impact on prognosis. Only two cases were MSI high. The results support the hypothesis of two aetiological pathways in pSCC cancerogenesis: (1) SCC linked to HPV infection characterised by low TMB, less common PD-L1 expression, and a lower number of TILs; and (2) SCC linked to chronic inflammation leading to a high number of acquired mutations (high TMB), HPV negativity, increased neoantigen production (i.e., PD-L1), and high immune cell infiltration.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

<a href="/cs/project/NU21J-03-00019" target="_blank" >NU21J-03-00019: Prognosticky významné prediktivní znaky karcinomu penisu: molekulární a morfologická studie.</a><br>

Návaznosti

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

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

Pathology

ISSN

0031-3025

e-ISSN

1465-3931

Svazek periodika

56

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

10

Strana od-do

357-366

Kód UT WoS článku

001236901100001

EID výsledku v databázi Scopus

2-s2.0-85181254256