Immunohistochemical analysis of glassy cell carcinoma of the cervix reveals robust lymphocyte infiltrate and the expression of targetable inhibitory immune checkpoints.

OBJECTIVE: To validate our previous findings of high-level EGFR expression in GCCC using an expanded cohort of specimens and to further examine the molecular and cellular features of this aggressive malignancy to identify potentially actionable therapeutic targets. METHODS: The SEER database was queried to obtain the epidemiological data regarding the current national survival trends for GCCC. Immunohistochemistry (IHC) was used to examine the expression of EGFR, PD-1, and PD-L1. CiberSort analysis was used to analyze a previously published RNA-sequencing dataset obtained from a single patient diagnosed with GCCC. RESULTS: In comparison to squamous cell carcinomas and adenocarcinoma/adenosquamous carcinomas, GCCC was observed in younger patients (p < 0.001) and demonstrated inferior survival (p < 0.001). All (100%) of the specimens (8/8) exhibited immunoreactivity when stained for CD3ε (T-cell marker), EGFR, PD-1, and PD-L1 whereas CTLA4 expression was not detected. Analysis of RNA-sequencing data revealed that cetuximab and erlotinib altered the chemokine profile, lymphocyte abundance, and expression of inhibitory immune checkpoints in a single patient when combined with cytotoxic chemotherapy in a single patient. CONCLUSIONS: The data from this descriptive study suggests that immune checkpoint blockade, whether single agent or in combination, may be a suitable therapeutic option for a disease for which targeted approaches do not currently exist.

Molecular Genetic Profiling of Adolescent Glassy Cell Carcinoma of the Cervix Reveals Targetable EGFR Amplification with Potential Therapeutic Implications.

Glassy cell carcinoma of the cervix (GCCC) is a very rare and aggressive form of cervical cancer. An adolescent female with advanced metastatic disease was enrolled in our genomic profiling research protocol. We identified high-level amplification of epidermal growth factor receptor (EGFR) and Yes-associated protein-1 (YAP1), which led to the addition of EGFR inhibitors to the chemotherapy regimen. Here, we report the first genetically profiled case of GCCC with potential therapeutic implications.