RESUMO
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.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Proteínas com Domínio LIM/metabolismo , Glicoproteínas de Membrana/metabolismo , Papillomaviridae/genética , Infecções por Papillomavirus/metabolismo , Fatores de Transcrição/metabolismo , Neoplasias Vulvares/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/virologia , DNA Viral/genética , Feminino , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/virologia , Prognóstico , Análise de Sobrevida , Neoplasias Vulvares/virologiaRESUMO
The incidence rate of tonsillar cancer is increasing worldwide. The current study identifies a parallel increase in the incidence of tonsillar cancer, human papilloma virus (HPV) and p16 expression among a population from northern Sweden, a sparsely populated area, confirming the strong association between p16 and HPV infection in tonsillar tissue. Data from the Swedish Cancer Registry was assessed to identify cases of tonsillar cancer in the northern territorial area of Sweden. HPV DNA was extracted from paraffin embedded diagnostic biopsies and detected by polymerase chain reaction using general primers Gp5+/6+ and CpI/IIG. Expression of p16 was identified by immunochemistry. Patients were grouped into urban or rural residence categories. A total of 214 cases were identified, comprising 155 (72.4%) men and 59 (27.6%) women, and 65 of these patients, who presented between 2000 and 2012, were analyzed. The overall median age for the analyzed patients was 58 years; 48 (74%) were males (median age, 57.5 years) and 17 (26%) were females (median age, 65 years). Of the 65 specimens, 59 (91%) were positive for HPV, and 62 (95%) expressed p16. The incidence of tonsillar cancer in the cohort demonstrated a 2-fold increase between 1990 and 2013; specifically, a 2.7-fold increase was observed in men whilst the female group exhibited only a small increase. These findings demonstrate a strong association between p16 expression and HPV infection in tonsillar malignancies. The incidence of HPV-positive tonsillar cancer has increased in recent years, even in sparsely populated regions, as demonstrated in northern Sweden.