Evaluation of clear cell subtypes of ovarian and uterine malignancies with anti-PD-L1 and anti-PD1 immunohistochemical expression and their association with stage and survival

Alldredge, Jill; Serna-Gallegos, Tasha; Gallegos, Nicolas; Vanleer, Jessica; Chang, Jenny; Ziogas, Argyrios; Goreal, Wamda; Randall, Leslie M.

doi:10.1016/j.ygyno.2019.10.008

Cited by 7 publications

(8 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PD-L1 is reportedly expressed in CCC of the ovary and uterine endometrium [22,23]. Willis Journal of Immunology Research of ovarian and endometrial CCCs, respectively [23]. In the present study, PD-L1 was positive in 22% (11/50) of the cervical CCC samples.…”

Section: Discussionsupporting

confidence: 57%

“…Taken together, our data suggest that the B7 family of immune checkpoints play nonredundant and The morphologic features of cervical CCC are similar to those of the ovary and uterine endometrium, comprising eosinophilic and hobnail cells with clear cytoplasm arranged in tubulocystic, papillary, or solid patterns. PD-L1 is reportedly expressed in CCC of the ovary and uterine endometrium [22,23]. Willis Journal of Immunology Research of ovarian and endometrial CCCs, respectively [23].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Expression and Significance of Immune Checkpoints in Clear Cell Carcinoma of the Uterine Cervix

Zong

Zhang

Zhou

et al. 2020

Journal of Immunology Research

View full text Add to dashboard Cite

The purpose of this study was to investigate the expression levels of the immune checkpoint proteins, programmed cell death-ligand 1 (PD-L1), B7-H3, B7-H4, and V-domain Ig suppressor of T cell activation (VISTA), as well as the significance thereof, in clear cell carcinoma (CCC) of the cervix (a rare histological subtype of cervical cancer). We also compared the expression statuses of these biomarkers in cervical CCCs with those in cervical squamous cell carcinomas (SCCs). We evaluated the expression of PD-L1, B7-H3, B7-H4, and VISTA in 50 cervical CCCs and 100 SCCs using immunohistochemical staining and investigated the associations between these markers, clinicopathologic features, and survival in patients with CCCs. Of the cervical CCC samples examined, 22%, 16%, 32%, and 34% were positive for PD-L1, B7-H3, B7-H4, and VISTA, respectively. Nineteen samples (38%) were negative for all 4 of these markers, whereas 31 (62%) expressed at least 1 marker. None of these markers was associated with the investigated clinicopathologic variables or patient survival. PD-L1, B7-H3, and VISTA were observed significantly more frequently in SCCs than in CCCs of the cervix. Our study confirmed the expression of immune checkpoint proteins in cervical CCCs and indicated their nonredundant and complementary roles. As such, our data suggest that monotherapeutic immune checkpoint blockade may not be sufficiently effective in patients with cervical CCC.

show abstract

Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Expression and Significance of Immune Checkpoints in Clear Cell Carcinoma of the Uterine Cervix

Zong

Zhang

Zhou

et al. 2020

Journal of Immunology Research

View full text Add to dashboard Cite

show abstract

“…The CPS results were reported as <1 or ≥1 ( 16 ). Immunohistochemical expression of PD-L1 in ovarian and uterine CCC has been in explored in further detail in a larger cohort, from which this patient sample was selected ( 17 ).…”

Section: Methodsmentioning

confidence: 99%

“…Tumor growth and responsiveness to therapy have foundations in tumor-induced immune suppression, primarily regulated by programmed death-ligand 1 (PD-L1), which promotes a regulatory T cell population and thereby facilitates immune evasion. The immunohistochemical expression of PD-L1 is correlated with poor outcomes in renal CCC (5) and ovarian CCC (6). Additionally, mutations in TP53, PIK3CA, PRKC1, and KRAS oncogenes as well as ARID1A and PTEN tumor suppressor genes have been studied as key drivers of ovarian CCCs, revealing therapeutic targets (7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Transcriptome Analysis of Ovarian and Uterine Clear Cell Malignancies

Alldredge¹,

Randall

Robles

et al. 2020

Front. Oncol.

Self Cite

View full text Add to dashboard Cite

PurposeOvarian and uterine clear cell carcinomas (CCCs) are rare but associated with poor prognosis. This study explored RNA transcription patterns characteristic of these tumors.Experimental DesignRNA sequencing (RNA-seq) of 11 ovarian CCCs and five uterine CCCs was performed and compared to publicly available data from high grade serous ovarian cancers (HGSOCs). Ingenuity Pathway Analyses were performed. CIBERSORT analyses estimated relative fractions of 22 immune cell types in each RNA-seq sample. Sequencing data was correlated with PD-L1 immunohistochemical expression.ResultsRNA-seq revealed 1,613 downregulated and 1,212 upregulated genes (corrected p < 0.05, |FC |≥10) in ovarian CCC versus HGSOC. Two subgroups were identified in the ovarian CCC, characterized by ethnicity and expression differences in ARID1A. There were 3,252 differentially expressed genes between PD-L1+/− ovarian CCCs, revealing immune response, cell death, and DNA repair networks, negatively correlated with PD-L1 expression, whereas cellular proliferation networks positively correlated with expression. In clear cell ovarian versus clear cell uterine cancer, 1,607 genes were significantly upregulated, and 109 genes were significantly downregulated (corrected p < 0.05, |FC|≥10). Comparative pathway analysis of late and early stage ovarian CCCs revealed unique metabolic and PTEN pathways, whereas uterine CCCs had unique Wnt/Ca+, estrogen receptor, and CCR5 signaling. CIBERSORT analysis revealed that activated mast cells and regulatory T cell populations were relatively enriched in uterine CCCs. The PD-L1+ ovarian CCCs had enriched resting NK cells and memory B cell populations, while PD-L1− had enriched CD8 T-cells, monocytes, eosinophils, and activated dendritic cells.ConclusionsUnique transcriptional expression profiles distinguish clear cell uterine and ovarian cancers from each other and from other more common histologic subtypes. These insights may aid in devising novel therapeutics.

show abstract

“…Subgroup 1 contained 66% white patients (4/6 white and 2/6 unknown), whereas subgroup 2 contained 80% women of Asian ancestry (4/5 Asian and 1/5 white). Using a larger ovarian CCC IHC-only cohort of 30 patients from which our pilot population was derived, Kaplan-Meier analysis of disease-specific overall survival suggests a trend that White women with ovarian CCC may have worse overall survival at a median 53.8 months compared to Asian American women at a median 4,101 months (p = 0.29) ( Figure 1C) (6) (17).…”

Section: Subcategorization Of Clear Cell Ovarian Cancermentioning

confidence: 99%

Table_2.xlsx

View full text Add to dashboard Cite

Evaluation of clear cell subtypes of ovarian and uterine malignancies with anti-PD-L1 and anti-PD1 immunohistochemical expression and their association with stage and survival

Cited by 7 publications

References 18 publications

Expression and Significance of Immune Checkpoints in Clear Cell Carcinoma of the Uterine Cervix

Expression and Significance of Immune Checkpoints in Clear Cell Carcinoma of the Uterine Cervix

Transcriptome Analysis of Ovarian and Uterine Clear Cell Malignancies

Table_2.xlsx

Contact Info

Product

Resources

About