A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Molecular subclassification of vulvar squamous cell carcinoma: reproducibility and prognostic significance of a novel surgical technique
Tekijät: Thompson Emily F, Hoang Lynn, Höhn Anne Kathrin, Palicelli Andrea, Talia Karen L, Tchrakian Nairi, Senz Janine, Rusike Rosebud, Jordan Suzanne, Jamieson Amy, Huvila Jutta, McAlpine Jessica N, Gilks C Blake, Höckel Michael, Singh Naveena, Horn Lars-Christian
Kustantaja: BMJ Publishing Group
Julkaisuvuosi: 2022
Journal: International Journal of Gynecological Cancer
Tietokannassa oleva lehden nimi: INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
Lehden akronyymi: INT J GYNECOL CANCER
Vuosikerta: 32
Numero: 8
Aloitussivu: 977
Lopetussivu: 985
Sivujen määrä: 9
ISSN: 1048-891X
eISSN: 1525-1438
DOI: https://doi.org/10.1136/ijgc-2021-003251
Verkko-osoite: https://ijgc.bmj.com/content/32/8/977
Objectives
Vulvar squamous cell carcinoma is subclassified into three prognostically relevant groups: (i) human papillomavirus (HPV) associated, (ii) HPV independent p53 abnormal (mutant pattern), and (iii) HPV independent p53 wild type. Immunohistochemistry for p16 and p53 serve as surrogates for HPV viral integration and TP53 mutational status. We assessed the reproducibility of the subclassification based on p16 and p53 immunohistochemistry and evaluated the prognostic significance of vulvar squamous cell carcinoma molecular subgroups in a patient cohort treated by vulvar field resection surgery.
Methods
In this retrospective cohort study, 68 cases treated by vulvar field resection were identified from the Leipzig School of Radical Pelvic Surgery. Immunohistochemistry for p16 and p53 was performed at three different institutions and evaluated independently by seven pathologists and two trainees. Tumors were classified into one of four groups: HPV associated, HPV independent p53 wild type, HPV independent p53 abnormal, and indeterminate. Selected cases were further interrogated by (HPV RNA in situ hybridization, TP53 sequencing).
Results
Final subclassification yielded 22 (32.4%) HPV associated, 41 (60.3%) HPV independent p53 abnormal, and 5 (7.3%) HPV independent p53 wild type tumors. Interobserver agreement (overall Fleiss' kappa statistic) for the four category classification was 0.74. No statistically significant differences in clinical outcomes between HPV associated and HPV independent vulvar squamous cell carcinoma were observed.
Conclusion
Interobserver reproducibility of vulvar squamous cell carcinoma subclassification based on p16 and p53 immunohistochemistry may support routine use in clinical practice. Vulvar field resection surgery showed no significant difference in clinical outcomes when stratified based on HPV status.