Malignant Transformation Of Sinonasal Inverted Papilloma Research Articles

Sinonasal inverted papilloma - malignant transformation and non-sinonasal malignancies.

To assess malignant transformation rate, non-sinonasal malignancies, and factors contributing to recurrence in patients treated for sinonasal inverted papilloma (SNIP). Retrospective study. We retrospectively reviewed medical records of all patients treated for SNIP (n=296) between the years 1984-2014 at Helsinki University Hospital. Data from the Finnish Cancer Registry confirmed the number of those patients with sinonasal and non-sinonasal malignancies. Only 2 of 296 (0.7%) patients primarily diagnosed with benign SNIP developed sinonasal cancer in a mean follow-up of 5.8 years. The most common non-sinonasal cancer sites were similar to those reported for the whole Finnish population. None of the patients presented with an HPV-associated non-sinonasal malignancy. The recurrence rate among patients who underwent attachment-oriented surgery was significantly lower compared to those operated on with other approaches (40.2% vs. 56.6%, p=0.006). Dysplasia in SNIP was associated with a higher recurrence rate (p < 0.001). Malignant transformation of SNIP was rare. Patients with SNIP were not prone to HPV-associated non-sinonasal malignancies. Endoscopic resection and attachment-oriented surgery have become predominant approaches in the treatment of SNIP; meanwhile, the total number of SNIP recurrences has decreased. 3 Laryngoscope, 133:506-511, 2023.

Putative biomarkers of malignant transformation of sinonasal inverted papilloma into squamous cell carcinoma.

ObjectiveTo compare genome-wide DNA methylation between samples of sinonasal inverted papilloma (SNIP) and squamous cell carcinoma (SCC) samples in order to identify aberrantly methylated genes that might be involved in malignant transformation.MethodsTissue samples were collected from patients. DNA methylation in C-phosphate-G islands and gene promoters was analysed using a DNA methylation microarray kit. The levels of mRNA or protein from aberrantly methylated genes were measured using real-time polymerase chain reaction or Western blot analysis.ResultsA total of 27 tissue samples were included in this study; 15 SNIP samples and 12 SCCs arising in SNIPs. A total of 11 201 nominally differentially methylated sites were observed between SNIP and SCC arising in SNIPs. Six sites were significantly different at P < 0.01 and contained three genes (MIR661, PLEC and OPA3). These three genes were hypermethylated. In addition, the levels of mature miR-661 mRNA and PLEC protein were significantly upregulated in SCC tissues compared with SNIP samples. The levels of OPA3 protein were downregulated in SCC tissues compared with SNIP samples.ConclusionsThis study demonstrated hypermethylation and abnormal expression of the MIR661, PLEC and OPA3 genes, suggesting a role for their involvement in the malignant transformation of SNIP.

Comprehensive analysis of HPV infection, EGFR exon 20 mutations and LINE1 hypomethylation as risk factors for malignant transformation of sinonasal-inverted papilloma to squamous cell carcinoma.

Different risk factors are suspected to be involved in malignant transformation of sinonasal papillomas and include HPV infection, tobacco smoking, occupational exposure, EGFR/KRAS mutations and DNA methylation alterations. In our study, 25 inverted sinonasal papillomas (ISPs), 5 oncocytic sinonasal papillomas (OSP) and 35 squamous cell carcinomas (SCCs) from 54 patients were genotyped for 10 genes involved in EGFR signalling. HPV-DNA detection was performed by in-situ hybridisation and LINE-1 methylation was quantitatively determined by bisulphite-pyrosequencing. High-risk HPV was observed only in 13% of ISP-associated SCC and in 8% of de novo-SCC patients. EGFR mutations occurred in 72% of ISPs, 30% of ISP-associated SCCs and 17% of de novo-SCCs. At 5-year follow-up, SCC arose in only 30% (6/20) of patients with EGFR-mutated ISPs compared to 76% (13/17) of patients with EGFR-wild-type ISP (p = 0.0044). LINE-1 hypomethylation significantly increased from papilloma/early stage SCC to advanced stage SCC (p = 0.03) and was associated with occupational exposure (p = 0.01) and worse prognosis (p = 0.09). In conclusion, our results suggest that a small subset of these tumours could be related to HPV infection; EGFR mutations characterise those ISPs with a lower risk of developing into SCC; LINE-1 hypomethylation is associated with occupational exposure and could identify more aggressive nasal SCC.

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

Schneiderian papillomas are uncommon tumors which may develop within the nasal cavity and comprise three well-defined histological types: sinonasal inverted papilloma (SNIP), exophytic papilloma, and oncocytic papilloma. It is well known the rate of Schneiderian papilloma may also present a malignant degeneration and SNIP represents the most important subgroup in consideration of its frequency and malignant propensity. Although HPV infection is always considered the first event favoring the development of SNIP, however, it is not established as an eventual connection between viral actions and malignant transformation. In fact, different molecular mechanisms are suspected to play a crucial role in this process and, currently, many authors agree that only by improving our knowledge about these mechanisms it will be possible to achieve new and effective targeted therapies. So the aim of this study was firstly to systematically review the literature focusing on different biomarkers that could be implicated in the stages of SNIP malignant degeneration. Secondly, a systematic review with meta-analysis was performed to better define the incidence of sinonasal malignancies originating from Schneiderian papilloma (SNIP, exophytic papilloma, and oncocytic papilloma). Twenty-nine studies comprising a total of 3177 patients were statistically analyzed. Results showed a 9% (95% CI=7-11) overall rate of malignant transformation from Schneiderian papilloma. In conclusion, this analysis confirmed that the potential malignancy of Schneiderian papilloma should not be underestimated. On the other hand, our review showed the paucity of studies investigating the molecular alterations which may be related with the malignant transformation of SNIP.

Human topoisomerase II‐α is highly expressed in sinonasal‐inverted papilloma, but not in inflammatory polyp

Sinonasal-inverted papilloma is a benign tumour with a high rate of recurrence, but possible malignant transformation. Therefore, inves tigation of predisposition to malignant transformation of sinonasal-inverted papilloma gives clinicians the opportunity for adequate trea ment. Topoisomerase II-α (topoII-α) and Ki67 are markers of cell proliferation in both normal and neoplastic tissues and its level o expression could be used as a predictive parameter. Our goal was to investigate by immunochemistry the expression level of topoII-in inverted papilloma, inflammatory nasal polyp and normal sinonasal epithelium and to compare it with expression level of Ki67. TopoI α nuclear immunostaining showed a differential positivity in the investigated cases. The topoII-α index was 30.6 ± 12.8 in inverte papilloma, 10.7 ± 6.6 in the adjacent epithelium of inverted papilloma, but only 2.3 ± 2.0 in the normal sinonasal epithelium. The di ferences in topoII-α expression between inverted papilloma and normal sinonasal epithelia were statistically significant. In inflammator nasal polyp group, topoII-α index was 2.4 ± 2.1, and the difference in the topoII-α index between inverted papilloma and inflammator polyp group was also statistically significant. Nuclear immunostaining for Ki67 followed a similar variation. The Ki67 index was 50.0 ± 20. in inverted papilloma, 9.0 ± 6.6 in the adjacent epithelium of inverted papilloma and 2.4 ± 0.9 in normal sinonasal epithelium. The di ferences in Ki67 expression between inverted papilloma and either adjacent or normal sinonasal epithelia were statistically significan Significant correlation coefficients were found between topoII-α and epithelial thickness (r = 0.70, P > 0.0001), and between Ki67 inde and epithelial thickness (r = 0.71, P> 0.0001). In the inflammatory nasal polyp group Ki67 index was 5.9 ± 3.4. The difference in th Ki67 index between inverted papilloma and inflammatory nasal polyp groups was statistically significant. Significant correlation coeff cient was found between topoII-α index and Ki67 index in inverted papilloma (r = 0.42, P > 0.05). These results suggest that the inverte papilloma contains a significantly higher cell population with proliferative activity by comparison with normal sinonasal and inflamma tory polyp epithelia, showing a significant correlation between topoII-α and Ki67 expression, and indicating that topoII-α could be a independent prognostic factor for a putative malignant transformation.