Cyclin D1 Overexpression Predicts Poor Disease-Specific Survival in Human Papillomavirus-Independent Vulvar Squamous Cell Carcinoma
Carreras-Dieguez, Núria (Hospital Clínic i Provincial de Barcelona)
Ordi, Oriol (Universitat de Barcelona)
Peñuelas, Núria (Universitat de Barcelona)
del Pino, Marta (Universitat de Barcelona)
Diez-Ahijado, Laia (Hospital Clínic i Provincial de Barcelona)
Darecka, Katarzyna (Hospital Clínic i Provincial de Barcelona)
Marimon, Lorena (Hospital Clínic i Provincial de Barcelona)
Vega, Naiara (Hospital Clínic i Provincial de Barcelona)
Torné, Aureli (Universitat de Barcelona)
Saco, Adela (Hospital Clínic i Provincial de Barcelona)
Albero, Robert (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Gaba, Lydia (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Rakislova, Natalia (Hospital Clínic i Provincial de Barcelona)

Fecha:	2025
Resumen:	The amplification of CCND1 is associated with the development and progression of various cancers. In a recent study, we showed that almost all adverse outcomes in vulvar squamous cell carcinomas (VSCC) occurred in patients with human papillomavirus (HPV)-independent, TP53-mutated tumors harboring CCND1 gains. In this study, we analyzed the association between CCND1 gain, cyclin D1 immunohistochemistry (IHC), and disease-specific survival (DSS) in a series of patients with HPV-independent VSCC. All patients who underwent primary surgery for VSCC at the Hospital Clínic of Barcelona, Spain, from 1975 to 2023 were recruited ("overall" cohort, n = 139). IHC for p53 and cyclin D1 was performed in all cases. In a subset of patients, we performed DNA sequencing to evaluate CCND1 copy number variations ("sequencing" cohort, n = 54). Cyclin D1 IHC overexpression (≥50% of tumor cells) had 94% sensitivity and 67% specificity as a surrogate marker of CCND1 gain. In the "sequencing" cohort, only CCND1 gains were significantly associated with impaired DSS in the multivariate analysis (hazard ratio [HR], 4. 15; 95% CI, 1. 08-5. 40; P =. 032), whereas stage or mutant TP53 status did not reach statistical significance. In the "overall" cohort, advanced stage (HR, 2. 41; 95% CI, 1. 08-5. 39; P =. 032) and cyclin D1 IHC overexpression (HR, 4. 89; 95% CI, 1. 77-18. 5; P =. 001) were associated with worse DSS in the multivariate analysis, whereas abnormal p53 IHC was not (HR, 5. 06; 95% CI, 0. 68-647; P =. 138). In conclusion, cyclin D1 overexpression is an acceptable surrogate for CCND1 gain and has a much stronger adverse prognostic impact than altered p53 IHC in patients with HPV-independent VSCC.
Ayudas:	Instituto de Salud Carlos III PI14/00355 Instituto de Salud Carlos III PI19/01838 Instituto de Salud Carlos III PI20/00368 Ministerio de Economía y Competitividad CM23/00136
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	CCND1 ; Cyclin D1 ; Human papillomavirus ; Vulvar squamous cell carcinoma
Publicado en:	Modern Pathology, Vol. 38 Núm. 11 (november 2025) , p. 100833, ISSN 1530-0285

DOI: 10.1016/j.modpat.2025.100833

11 p, 1.6 MB

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