Expression of p16 in Sinonasal Undifferentiated Carcinoma (SNUC) Without Associated Human Papillomavirus (HPV)

Abstract

Sinonasal undifferentiated carcinoma (SNUC) is an uncommon and highly aggressive neoplasm of the paranasal sinuses and nasal cavity. Its undifferentiated histologic appearance often requires immunohistochemical studies to distinguish it from other high-grade neoplasms. Due to the rarity of SNUC, its immunohistochemical staining profile has been incompletely characterized, and little work has been done on its expression of the markers for human papillomavirus (HPV). Our objective is to expand our knowledge of its immunophenotype and its association with HPV in order to define markers with mechanistic potential in the disease process, or of possible therapeutic importance. A total of five patients (one woman and four men) with SNUC, ranging in age from 26 to 75 years (mean 56.8 years) were compared to five patients (five men) with poorly differentiated squamous cell carcinoma (PDSCC), ranging in age from 53 to 75 years (mean 62.2 years). PDSCC was chosen as a control, given its well-reported immunohistochemical profile and negativity for HPV markers. The immunohistochemical panel included: CK7, CK19, EMA, NSE, chromogranin, p53, CK5/6, p63, CK14, S100, HMB-45, desmin, muscle specific actin, and CD45. Additionally, tests for p16, EBV, and HPV (subtypes 6, 11 16, 18) were performed. The diagnosis of SNUC was confirmed in all cases by histology and immunohistochemical stains. An interesting finding of strong diffuse positivity for p16 was noted in all SNUC cases, compared to only two of five PDSCC that were positive for p16. HPV DNA was not detected in any SNUC cases or any cases of PDSCC. All SNUC cases demonstrated over expression of p16 in the absence of HPV DNA expression. This may represent residual epithelial p16 staining, which is normally present in the sinonasal tract. Due to the rarity of SNUC, more cases will need to be evaluated to confirm the absence of HPV DNA.

Human Papillomavirus in Non-Oropharyngeal Head and Neck Cancers: A Systematic Literature Review

“…status, detected by either PCR or ISH, and diffuse p16 overexpression, has been reported in sinonasal SCC, albeit in small numbers [97,[119][120][121]. Strong diffuse p16 expression cannot be accepted as a surrogate HPV biomarker in any untested context, as this pattern of overexpression has also been detected in HPV-negative sinonasal undifferentiated carcinoma [122]. The improved outcome associated with HPV?…”

p16 Immunohistochemistry As a Standalone Test for Risk Stratification in Oropharyngeal Squamous Cell Carcinoma

“…'' The concept that a minority of patients whose tumors are p16 positive actually lack HPV is probably partially driven by speculation on tumor biology but also likely by findings for p16 and HPV-specific tests in other cancer types. For example, in sinonasal undifferentiated carcinomas, most of the tumors overexpress p16 but none have been found to harbor HPV [17]. Similarly, in several types of lung non-small cell carcinoma, p16 is overexpressed in as many as 60% of cases, unassociated with the presence of HPV [18].…”

A multimodality approach to sinonasal undifferentiated carcinoma: a single institute experience

“…Immunohistochemical analysis reveals that these cells are immunoreactive for cytokeratin and show patchy staining for neuronspecific enolase and epithelial membrane antigen. 3,12 Surgery is considered the cornerstone of therapy. 13 Owing to non-specific symptoms, a third of patients present with extensive local tumours that are unsuitable for surgical resection.…”

“…1 Sinonasal undifferentiated carcinoma predominantly affects men in the fifth decade of life. 2,3 Neck nodal involvement can occur in 10 per cent of patients, although rates as high as 28 per cent have been reported. 4,5 Hematogenous metastasis, although uncommon, is reported to involve the lung, liver, brain and bone.…”