LRIG1-2 and LMO7 immunoreactivity in vulvar squamous cell carcinoma: Association with prognosis in relation to HPV-DNA and p16(INK4a) status

The present study was conducted to investigate the possible prognostic value of molecular markers LRIG1-2 and LIM domain 7 protein (LMO7) in vulvar squamous cell carcinoma (VSCC) and their possible correlation to human papilloma virus (HPV)- and p16(INK4a)-status of the tumors. Patients diagnosed with VSCC at the University Hospital of Umeå, Sweden, during the years 1990–2013 were selected. Tumor blocks were retrieved from tissue archives and clinical data were collected from the records of patients. HPV-PCR analysis, HPV genotyping and immunohistochemistry were performed. In total, 112 patients were included. Forty percent of the tumors were HPV-positive, 27% were p16(INK4a)-positive and 23% were positive for both HPV and p16(INK4a) (considered HPV-driven). HPV-positivity and p16(INK4a)-positivity were associated with prolonged disease-free survival (DFS) in Kaplan-Meier survival analysis. Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) immunoreactivity was not significantly associated with survival. High leucine-rich repeats and immunoglobulin-like domains 2 (LRIG2) immunoreactivity was associated with a prolonged overall survival (OS) (P=0.001). By analyzing HPV-negative cases only, it was determined that high LRIG2 immunoreactivity was associated with both favorable OS (P=0.008) and DFS (P=0.031). LRIG2 immunoreactivity was also an independent prognostic factor in multivariate analysis of OS (P=0.002, HR=0.41; 95% CI, 0.24-0.71). High immunoreactivity with LMO7-1250 antibody was associated with survival benefits in the whole cohort (OS; P=0.011) although DFS was only prolonged in HPV-negative and not HPV-driven tumors (P=0.038 and 0.042, respectively). The present study indicated that LRIG2 and LMO7 may be useful prognostic markers in VSCC, particularly for patients without HPV-driven tumors or with advanced tumors at diagnosis. In contrast to earlier observations regarding other types of squamous cell carcinoma, LRIG1 was not a significant prognostic factor in VSCC.