LRIG1­2 and LMO7 immunoreactivity in vulvar squamous cell carcinoma: Association with prognosis in relation to HPV­DNA and p16INK4a status.

The present study was conducted to investigate the possible prognostic value of molecular markers LRIG1­2 and LIM domain 7 protein (LMO7) in vulvar squamous cell carcinoma (VSCC) and their possible correlation to human papilloma virus (HPV)­ and p16INK4a­status of the tumors. Patients diagnosed with VSCC at the University Hospital of Umeå, Sweden, during the years 1990­2013 were selected. Tumor blocks were retrieved from tissue archives and clinical data were collected from the records of patients. HPV­PCR analysis, HPV genotyping and immunohistochemistry were performed. In total, 112 patients were included. Forty percent of the tumors were HPV­positive, 27% were p16INK4a­positive and 23% were positive for both HPV and p16INK4a (considered HPV­driven). HPV­positivity and p16INK4a­positivity were associated with prolonged disease­free survival (DFS) in Kaplan­Meier survival analysis. Leucine­rich repeats and immunoglobulin­like domains 1 (LRIG1) immunoreactivity was not significantly associated with survival. High leucine­rich repeats and immunoglobulin­like domains 2 (LRIG2) immunoreactivity was associated with a prolonged overall survival (OS) (P=0.001). By analyzing HPV­negative 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, 0.24­0.71). High immunoreactivity with LMO7­1250 antibody was associated with survival benefits in the whole cohort (OS; P=0.011) although DFS was only prolonged in HPV­negative and not HPV­driven 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 HPV­driven 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.