Clinicopathological and immune characterization of mismatch repair deficient endocervical adenocarcinoma

Ying-Wen Wu ^1,2,3, Li-Jun Wei ^1,2, Xia Yang ^1,2

⁰Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, People's Republic of China.

The Oncologist +

|

August 7, 2024

View abstract on PubMed

Summary

Mismatch repair deficiency (dMMR) endocervical adenocarcinomas (ECAs) show distinct features and a unique immune microenvironment. Identifying dMMR ECAs may improve immunotherapy responses in this aggressive cancer.

Area Of Science

Oncology
Immunology
Pathology

Background

Endocervical adenocarcinoma (ECA) is increasingly diagnosed in young women, often presenting as an aggressive disease with limited targeted therapy options.
Mismatch repair deficiency (dMMR) is a key biomarker for predicting response to immune checkpoint inhibitors (ICIs).

Purpose Of The Study

To investigate the clinicopathological features and immune microenvironment of dMMR ECAs.
To identify potential biomarkers for immunotherapy in ECA.

Main Methods

Analysis of 617 ECA cases using tissue microarrays.
Immunohistochemical staining for MMR proteins, PD-L1, and other immune markers.
Correlation of dMMR status with clinicopathological and morphological variables.

Main Results

dMMR was identified in 3.2% of ECAs, with a higher prevalence in non-HPV-associated (NHPVA) and clear cell subtypes.
dMMR ECAs exhibited specific features: family history of cancer, larger size, p16 negativity, HPV E6/E7 RNAscope negativity, and lower Ki-67 index.
dMMR ECAs showed increased stromal and peritumoral lymphocytes, lymphoid follicles, and elevated expression of CD3, CD8, CD38, CD68, PD-1, and PD-L1.

Conclusions

dMMR ECAs possess distinct morphological characteristics and a significantly altered immune microenvironment.
These findings suggest that dMMR status is a critical factor influencing the immune landscape of ECAs and may predict response to immunotherapy.

Keywords:

endocervical adenocarcinoma immune microenvironment mismatch repair deficiency morphological characteristics programmed cell death ligand 1