Epidermal growth factor receptor, p16, cyclin D1, and p53 staining patterns for inverted papilloma

Abstract

Introduction We aim to better characterize the staining patterns of inverted papilloma (IP) with and without carcinoma by performing immunohistochemistry for p16, EGFR (Epidermal Growth Factor Receptor), p53, and Cyclin D1 antibodies on a large patient cohort. Methods One hundred and sixty-two IP specimens from 122 patients treated at the University of Michigan between 1996 and 2011. Twenty-two specimens contained carcinoma. Tumor was extracted for construction of two tissue microarrays and stained for p16, EGFR, p53, and Cyclin D1. Tumor staining intensity and percentage staining were scored. Results Mean percentage staining for IP and IP with carcinoma was 12% versus 7% for p16 (no statistical significance, NS), 20% versus 34% for EGFR (NS), 4% versus 24% for p53 (p<0.001), and 17% versus 21% for Cyclin D1 (NS). Benign disease was positive for p16 in 64%, EGFR in 50%, p53 in 30%, and Cyclin D1 in 76%. Inverted papilloma with carcinomatous degeneration was positive for p16 in 14%, EGFR in 71%, p53 in 62%, and Cyclin D1 in 76%. This is statistically significant for differences between IP and IP carcinoma for p16 and p53 staining only. Conclusion Important characteristic staining pattern for inverted papilloma with and without carcinoma are highlighted in this study. Unlike recent trends in HPV-related head and neck malignancies, low expression of p16 is a marker for malignancy in this series. Positive staining for p53 correlates with the development of carcinoma in inverted papilloma.

Human papillomavirus infection and biomarkers in sinonasal inverted papillomas: clinical significance and molecular mechanisms

“…7 In contrast, in a previous study we reported that regardless of the HPV status high expression of p53 correlates with the presence of carcinoma in IPs. 12 Since decreased p53 levels appear to be a hallmark of high risk HPV induced tumors, this study’s results do not concur with the hypothesis that IPs malignant transformation is an HPV driven event.…”

“…12 A tissue microarray (TMA) was constructed, deparaffinized and rehydrated. The immunohistochemistry staining was then performed.…”

“…18,19 However in IPs p16 could not be established as a marker of HPV infection and low expression of p16 has been correlated with malignancy in IPs. 12,20 The absence of an elevated p16 expression in IPs harboring cancer does not support a model where high risk HPV E7 protein is a driver of malignant transformation.…”

“…We study the mechanisms of HPV pathogenesis in IPs using a detection of integrated papillomavirus sequences by ligation-mediated PCR (DIPS-PCR) assay modified for HPV 11 and complement this data with previously published immunohistochemistry for p53, p16, EGFR and cyclin D1. 12 …”

Malignant transformation of sinonasal inverted papilloma and related genetic alterations: a systematic review

“…A mutation in the p53 suppressor gene is one of the most common genetic changes in the pathogenesis of human cancer. Lin et al [30] suggested that p53 alteration is important in the progression of SNIPs to malignant disease. SNIPs with carcinoma stains positive for p53 at more than twice the frequency of SNIPs alone (62 versus 30%).…”