Article Text

Download PDFPDF

1071 The vulvar immunohistochemical panel (VIP) project: molecular profiles of vulvar squamous cell carcinoma
  1. G Garganese1,2,
  2. FS Inzani3,
  3. G Mantovani4,
  4. SM Fragomeni5,
  5. L Della Corte6,
  6. A Piermattei3,
  7. A Santoro3,
  8. G Angelico3,
  9. L Giacò7,
  10. G Corrado5,
  11. S Bove2,
  12. A Romito2,
  13. A Fagotti1,5,
  14. GF Zannoni3 and
  15. G Scambia1,5
  1. 1Università Cattolica del Sacro Cuore, Istituto di Clinica Ostetrica e Ginecologica, Rome, Italy
  2. 2Mater Olbia Hospital, Gynecology and Breast Care Center, Olbia, Italy
  3. 3Fondazione Policlinico Universitario A. Gemelli IRCCS, Unità di Gineco-Patologia e Patologia Mammaria, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Rome, Italy
  4. 4IRCCS Ospedale Sacro Cuore Don Calabria, Chirurgia Pelvica Mini-Invasiva, International School of Surgical Anatomy, Negrar di Valpolicella, Italy
  5. 5Fondazione Policlinico Universitario A. Gemelli IRCCS, Unità di Ginecologia Oncologica, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Rome, Italy
  6. 6University of Naples Federico II, Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, Naples, Italy
  7. 7Fondazione policlinico Universitario A. Gemelli IRCCS, Rome, Italy


Introduction/Background*Investigate the immunohistochemical (IHC) expression of biological markers as potential prognostic/therapeutic factors in vulvar squamous cell carcinoma (VSCC).

Methodology A series of 101 patients surgically treated at our Center from 2016 to 2020 were retrospectively enrolled: 53 node negative (Group A) and 48 node positive (Group B). A total of 146 samples, 101 primary tumor (T) and 45 nodal metastasis (N), were investigated. The IHC panel included: p16, p53, MLH1, MSH2, MSH6, PMS2, PD-L1, CD3, HER2/neu, ER, PR, EGFR, VEGF and CD31. The reactions were evaluated on qualitative and semi-quantitative scale. Generalized Linear Model (GLM) and Cluster analysis were performed in R statistical environment. A distance plot compared the IHC panel of T with the correspondent N.

Result(s)*Mismatch repair proteins (MMR), ER, PR and HER2/neu were excluded from data analysis because of homogeneous expression in all samples. Group A: the p16-positive expression (surrogate of HPV-dependent pathway) was significantly higher (20.8% vs 6.2%, p = 0.04). Group B: PD-L1-positive and high EGFR expression were found respectively in 77.1% and 97.9% patients, (T and/or N). Overall, p16-negative tumors showed a higher PD-L1 expression (60.9% vs. 50.0%). In both groups tumoral immune infiltration (CD3 expression), was mainly moderate/intense (80% vs. 95%). VEGF showed strong/moderate-diffuse expression in 13.9% of T samples. CD31 was used to study tumoral micro vessel density (MVD) with no difference between Group A and Group B. p53 and PD-L1 showed a significant association with nodal metastasis. Odds ratio (OR) for p53 mutation was 4.26 (CI 95% = 1.14 – 15.87, p = 0.03); OR for PD-L1 positivity was 2.68 (CI 95% = 1.0 – 7.19, p < 0.05).

The cluster analysis identified 3 and 4 sub-groups of molecular profiles respectively in Group A and B, with no different prognosis. Moreover, the molecular profile of each N and corresponding T diverged significantly in 18/41 (43.9%) cases.

Conclusion*These results support a potential role of immune checkpoint inhibitors and anti-EGFR drugs in a subset of patients with VSCC, especially with worse prognosis (metastatic, HPV-independent). It is mandatory to repeat the panel in the metastatic site to identify changes of marker expression.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.