PD-L1 expression and survival in p16-negative and -positive squamous cell carcinomas of the vulva

Czogalla, Bastian; Pham, Deborah Lan; Trillsch, Fabian; Rottmann, Miriam; Gallwas, Julia; Burges, Alexander; Mahner, Sven; Kirchner, Thomas; Jeschke, Udo; Mayr, Doris; Schmoeckel, Elisa

doi:10.1007/s00432-020-03126-9

Cited by 15 publications

(23 citation statements)

References 38 publications

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“…Our research group has already investigated a proven positive effect of p16 on the prognostic outcome of patients with VSCC. p16 positive VSCC revealed a longer overall and progression free survival [ 106 ]. It also appears in some other studies that HPV-associated VSCC have a better clinical outcome as Sand et al [ 107 ] reported in a recent review.…”

Section: Discussionmentioning

confidence: 99%

Combined COX-2/PPARγ Expression as Independent Negative Prognosticator for Vulvar Cancer Patients

et al. 2021

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Vulvar cancer incidence numbers have been rising steadily over the past decades. Especially the number of young patients with vulvar cancer increased recently. Therefore, the need to identify new prognostic factors for vulvar carcinoma is more apparent. Cyclooxygenase-2 (COX-2) has long been an object of scientific interest in the context of carcinogenesis. This enzyme is involved in prostaglandin synthesis and the latter binds to nuclear receptors like PPARγ. Therefore, the aim of this study was to investigate COX-2- and PPARγ- expression in tissues of vulvar carcinomas and to analyze their relevance as prognostic factors. The cytoplasmatic expression of COX-2 as well as PPARγ is associated with a significantly reduced survival, whereas nuclear expression of PPARγ results in a better survival. Especially the combined expression of both COX-2 and PPARγ in the cytoplasm is an independent negative prognosticator for vulvar cancer patients.

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Section: Discussionmentioning

confidence: 99%

Combined COX-2/PPARγ Expression as Independent Negative Prognosticator for Vulvar Cancer Patients

et al. 2021

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“…Sections from entire tumor blocks were used to account for the intratumoral heterogeneity and variability of the PD-L1 expression. They were processed as described previously [37]. Briefly, sections were cut from paraffin blocks and mounted on SuperFrost Plus ® microscopy slides (Menzel Gläser, Braunschweig, Germany).…”

Section: Analysis and Scoring Of Pd-l1 And P16 Expressionmentioning

confidence: 99%

“…Only the membranous reactivity of carcinoma cells was considered and quantified relating to the amount of vital carcinoma cells. For further analysis and stratification, we applied scores referred to as TPS 0 (TPS < 1%), TPS 1 (1% ≤ TPS < 5%), TPS 2 (5% ≤ TPS < 10%), TPS 3 (10% ≤ TPS < 25%), TPS 4 (25% ≤ TPS < 50%), and TPS 5 (TPS ≥ 50%) [37]. Positivity for p16 was defined by strong cytoplasmic and nuclear staining throughout the whole tumor on a slide ("block" staining).…”

Section: Analysis and Scoring Of Pd-l1 And P16 Expressionmentioning

confidence: 99%

Evaluation of PD-L1 Expression and HPV Genotyping in Anal Squamous Cell Carcinoma

Wessely

Heppt

Kammerbauer

et al. 2020

Cancers

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Anal squamous cell carcinoma (SCC) is a rare cancer with increasing incidence. Infection with high-risk human papillomavirus (HPV) subtypes is the major cause for its development. We retrospectively analyzed tumor samples from 54 anal SCC patients for infection with a panel of 32 HPV subtypes in a PCR-based approach, determined the PD-L1 expression status, and correlated the findings with the clinical data and the survival of the patients. Forty-two patients (77.8%) were HPV-positive and harbored at least one carcinogenic HPV subtype. HPV16 was the most frequently detected (n = 39, 72.2%). Four patients were infected with multiple HPV subtypes. HPV infection was significantly more often detected in female than in male patients (90.3% vs. 60.9%, p = 0.018). Patients with PD-L1 positive tumors showed a significantly better median overall survival (OS) compared with patients with PD-L1 negative tumors (69.3 vs. 28.3 months, p = 0.006). The median OS was significantly different among the distinct tumor stages (p = 0.029). Sex, grade of differentiation, and HPV infection status did not influence the median OS. Furthermore, HPV infection status and PD-L1 expression were not correlated. A multivariate Cox regression analysis revealed that PD-L1 expression status was an independent prognostic marker for survival (p = 0.012).

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“…Furthermore, there might be different definitions of p16 positivity in immunohistochemistry [ 43 ]. Exclusively strong cytoplasmic and nuclear “block like” staining throughout the whole tumor on slide should be considered as p16-positive [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

“…EP4 promotes its tumorigenic effect through several processes in the microtumor environment. Inter alia, previous studies identified PDL-1 expression as being a negative prognosticator in squamous cell carcinoma of the vulva and showed that the number of tumor infiltrating lymphocytes was associated with PD-L1 expression [ 44 ]. According to Wang et al, stimulation of PGE2/EP4 signaling pathways resulted in an increased expression of PD-1 in infiltrating CD8+ T-cells in patients with lung cancer [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

EP4 as a Negative Prognostic Factor in Patients with Vulvar Cancer

Buchholz

Vattai

Fürst

et al. 2021

Cancers

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New prognostic factors and targeted therapies are urgently needed to improve therapeutic outcomes in vulvar cancer patients and to reduce therapy related morbidity. Previous studies demonstrated the important role of prostaglandin receptors in inflammation and carcinogenesis in a variety of tumor entities. In this study, we aimed to investigate the expression of EP4 in vulvar cancer tissue and its association with clinicopathological data and its prognostic relevance on survival. Immunohistochemistry was performed on tumor specimens of 157 patients with vulvar cancer treated in the Department of Obstetrics and Gynecology, Ludwig-Maximilian-University of Munich, Germany, between 1990 and 2008. The expression of EP4 was analyzed using the well-established semiquantitative immunoreactivity score (IRS) and EP4 expression levels were correlated with clinicopathological data and patients’ survival. To specify the tumor-associated immune cells, immunofluorescence double staining was performed on tissue samples. In vitro experiments including 5-Bromo-2′-Deoxyuridine (BrdU) proliferation assay and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid (MTT) viability assay were conducted in order to examine the effect of EP4 antagonist L-161,982 on vulvar carcinoma cells. EP4 expression was a common finding in in the analyzed vulvar cancer tissue. EP4 expression correlated significantly with tumor size and FIGO classification and differed significantly between keratinizing vulvar carcinoma and nonkeratinizing carcinoma. Survival analysis showed a significant correlation of high EP4 expression with poorer overall survival (p = 0.001) and a trending correlation between high EP4 expression and shorter disease-free survival (p = 0.069). Cox regression revealed EP4 as an independent prognostic factor for overall survival when other factors were taken into account. We could show in vitro that EP4 antagonism attenuates both viability and proliferation of vulvar cancer cells. In order to evaluate EP4 as a prognostic marker and possible target for endocrinological therapy, more research is needed on the influence of EP4 in the tumor environment and its impact in vulvar carcinoma.

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PD-L1 expression and survival in p16-negative and -positive squamous cell carcinomas of the vulva

Cited by 15 publications

References 38 publications

Combined COX-2/PPARγ Expression as Independent Negative Prognosticator for Vulvar Cancer Patients

Combined COX-2/PPARγ Expression as Independent Negative Prognosticator for Vulvar Cancer Patients

Evaluation of PD-L1 Expression and HPV Genotyping in Anal Squamous Cell Carcinoma

EP4 as a Negative Prognostic Factor in Patients with Vulvar Cancer

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