Clinical relevance of p16 and p53 expression in HPV-negative Sinonasal Inverted Papillomas (SIPs)

Abstract

[한글]

[영문]Sinonasal inverted papillomas (SIPs) are recurrent and progressive unusual tumors of the nasal and paranasal sinus epithelium. Many reports have suggested human papilloma virus (HPV) infection is one of the causes of SIPs. However, the infection rates differ considerably among reporters, and pRb and p53 which are considered to interact with HPV viral genome were also affected in HPV-negative SIPs. p16 plays a critical role in the tumorigenesis of p16/cyclin D1/pRb pathway, and previous studies reported that p16 expression shows inverse relation with pRb which is usually inactivated due to HPV viral genome. Also, It has been reported that p53 shows reciprocal expression with HPV infection. However, p16 and p53 expressions according to disease courses such as recurrence or progression have not been studied along with HPV infection in SIPs. In this study, the clinical factors and representative proteins of cell cycle regulators, p16 and p53 were evaluated in patients with SIPs. HPV screening test were performed with 62 SIPs and they were sorted to control, recurrence and progression (to malignancy) groups. The semiquantitive scores for immunohistochemical stains of p16 and p53 (phosphorus and mutant form) and clinical factors such as sex, age, smoking history, operation methods, combined polyps, size of specimen, Krouse stage and time to recurrence and were compared between groups. The whole subjects were classified into four groups, p16+/p53-, p16-/p53-, p16+/p53+ and p16-/p53+, of which clinical factors also were compared. All SIPs showed HPV-negative, and endosopic surgery and advanced Krouse stage (p = 0.01 and p = 0.001, respectively) were associated with recurrence or progression. The p16 scored low (p = 0.004) and phosphorus and mutant forms of p53 (p = 0.001 and p = 0.014, respectively) scored highly in the recurrent or progression group significantly. There was difference of recurrence free survival (RFS) rate among alternative p16/p53 (phosphorus and mutant forms) groups significantly (p = 0.015 and p = 0.012, respectively), showing that the highest RFS rate was 82.4% in p16+/phosphorus form of p53- group and the lowest RFS rate was 33.3% in p16-/mutant form of p53+. In Kaplan-Meier analysis, the poorest disease courses were observed (p = 0.0003), demonstrating high possibility of recurrence in p16-/phosphorus form of p53+ group (p = 0.0009 vs p16-/mutant form of p53+ group).Thus, negativitiy of p16 and positivity of p53 might be related factors to poor clinical courses concerned with recurrence or progression and might be useful to predict disease course of HPV-negative SIPs at the first time of operation.