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24.07.2023 | Research

Protease-Activated Receptor 1 (PAR1) Expression Contributes to HPV-Associated Oropharyngeal Cancer Prognosis

verfasst von: Yoshinori Fujita, Yujiro Fukuda, Fumiaki Sanuki, Isao Irei, Yasumasa Monobe, Masako Uno, Takeshi Akisada, Koichiro Shimoya, Hirotaka Hara, Takuya Moriya

Erschienen in: Head and Neck Pathology | Ausgabe 3/2023

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Abstract

Background

Human papillomavirus (HPV)-associated oropharyngeal cancer occasionally has a poor prognosis, making prognostic risk stratification crucial. Protease-activated receptor-1 (PAR1) is involved in carcinogenesis, and its expression is regulated by alpha-arrestin domain-containing protein 3 (ARRDC3). It is also involved in the tumor microenvironment. We sought to evaluate the predictive ability of PAR1, ARRDC3, and tumor-infiltrating lymphocyte (TIL) scores in patients with oropharyngeal, hypopharyngeal, and uterine cervical cancers, serving as comparators for HPV-associated oropharyngeal cancer.

Methods

Immunohistochemical analysis of p16, ARRDC3, and PAR1 expression was performed on 79 oropharyngeal, 44 hypopharyngeal, and 42 uterine cervical cancer samples. The TIL scores were assessed and classified into the following groups based on invasion: low: 0–10%, medium: 20–40%, and high: > 50%. For prognostic analysis, the three groups were evaluated by dividing them into low, medium, and high categories, or alternatively into two groups using the median value as the cutoff.

Results

p16 was expressed in 44 (56%) oropharyngeal, 8 (18%) hypopharyngeal, and all uterine cervical cancer samples. ARRDC3 was detected in 39 (49%) oropharyngeal, 25 (57%) hypopharyngeal, and 23 (55%) uterine cervical cancer samples. PAR1 was expressed in 45 (57%) oropharyngeal, 22 (50%) hypopharyngeal, and 22 (50%) uterine cervical cancer samples. Patients diagnosed with p16-positive oropharyngeal cancer had a substantially improved prognosis compared to those diagnosed with p16-negative cancer. The PAR1-negative cases had a considerably improved prognosis compared to the positive cases (disease-specific survival [DSS] and -negative cases (disease-free survival [DFS]). Multivariate analysis revealed that ARRDC3-positive cases had an appreciably better DSS prognosis than patients with p16-negative oropharyngeal cancers. PAR1-positive patients among patients with p16-positive oropharyngeal cancer had a poor prognosis. With respect to DFS, patients with PAR1-positive and p16-negative oropharyngeal cancer had a 35-fold higher recurrence rate than those with PAR1-negative and p16-negative oropharyngeal cancer.

Conclusion

Our results suggest that PAR1 expression affects the prognosis and recurrence rate of HPV-associated oropharyngeal cancer.

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Titel: Protease-Activated Receptor 1 (PAR1) Expression Contributes to HPV-Associated Oropharyngeal Cancer Prognosis
verfasst von: Yoshinori Fujita
Yujiro Fukuda
Fumiaki Sanuki
Isao Irei
Yasumasa Monobe
Masako Uno
Takeshi Akisada
Koichiro Shimoya
Hirotaka Hara
Takuya Moriya
Publikationsdatum: 24.07.2023
Verlag: Springer US
Erschienen in: Head and Neck Pathology / Ausgabe 3/2023
Elektronische ISSN: 1936-0568
DOI: https://doi.org/10.1007/s12105-023-01567-5

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Protease-Activated Receptor 1 (PAR1) Expression Contributes to HPV-Associated Oropharyngeal Cancer Prognosis

Abstract

Background

Methods

Results

Conclusion

Neu im Fachgebiet Pathologie

Assistierter Suizid durch Infusion von Thiopental

Molekularpathologische Untersuchungen im Wandel der Zeit

Vergleichende Pathologie in der onkologischen Forschung

Gastrointestinale Stromatumoren

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Background

Methods

Results

Conclusion

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