Article Text
Abstract
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.