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

Result code in 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>

Alternative codes found

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

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30204 - Oncology

Project

<a href="/en/project/NU21J-03-00019" target="_blank" >NU21J-03-00019: The prognostic predictive markers in penile carcinoma: a molecular and morphological study.</a><br>

Continuities

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

Publication year

2024

Confidentiality

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

Name of the periodical

Pathology

ISSN

0031-3025

e-ISSN

1465-3931

Volume of the periodical

56

Issue of the periodical within the volume

3

Country of publishing house

GB - UNITED KINGDOM

Number of pages

10

Pages from-to

357-366

UT code for WoS article

001236901100001

EID of the result in the Scopus database

2-s2.0-85181254256