CD44 Expression in Sinonasal Inverted Papillomas and Associated Squamous Cell Carcinoma

Abstract

Increased expression of the cell adhesion molecule, CD44 standard form (CD44s), has been associated with papillary epithelial tumors, and decreased expression has been linked to tumor invasion and metastasis. Sinonasal inverted papillomas (SIPs) are the most common papillary tumors of the sinonasal tract. This study tests whether the development of squamous cell carcinoma (SCO in situ and invasive SCC in SIP is associated with altered expression of CD44s.Seventy-six specimens of SIP from 68 patients, 2 specimens of SIP with focal SCC in situ, and 10 specimens of invasive SCC arising in SIP were studied. Automated immunohistochemistry was performed for CD44s expression on paraffin-embedded tissue sections using mouse antihuman CD44 antibody.All 76 SIPs (100%) expressed CD44 (strong membranous staining, 83%; moderate staining, 12%; weak staining, 5%). TwoThe inverted papilloma is the most frequent benign mucosal neoplasm of the sinonasal tract.1-7 Sinonasal inverted papillomas (SIPs) are derived from the Schneiderian epithelium and occur most frequently during the fourth and fifth decades of life, with a male/female incidence ratio of 2:1.1 _ 6 Most commonly, SIP manifests as a unilateral nasal obstruction and features multiple mucosal sites of origin, reflecting a diffuse polypoid change of the nasal and paranasal sinus mucosa.6 Histologic features of SIP include squamous metaplasia of surface gland ducts and, frequently, branching gland ducts; stromal edema with infiltrates of lymphocytes, eosinophils, plasma cells, and m a c r o p h a g e s ; and n u m e r o u s macrophage-rich microcysts containing fragments of degenerated nuclear material.6 Although histologically benign, SIP features a substantial rate of recurrence after initial resection, which has varied from 33% to 74% in the published literature. [1][2][3][4][5][6] Squamous cell carcinoma (SCC) has been frequently associated with SIP since the first description by Hapman and Billroth in 1883/ Squamous cell carcinoma may be identified in the original excision of SIP or develop months or years after the first SIP excision, with roughly equal frequency. In published studies, the incidence of SCC associated with SIP has varied substantially. Woodson and c o w o r k e r s 8 reported an incidence of less than 2% of SCCs arising in SIP; Phillips and coworkers 9 reported a 7% incidence in 112 patients; and Bielamowicz et al 10 more recently reported a 17% cancer incidence in SIP.Cell adhesion molecules have been studied in a variety of papillary and nonpapillary epithelial neoplasms. CD44 is a polymorphic integral glycosylated cartilage link protein associated with cell matrix adhesion, lymphocyte activation and recirculation, and cell 309

CD44 Expression in Intraoral Salivary Ductal Papillomas and Oral Papillary Squamous Cell Carcinoma

“…In addition, in most cases, staining was limited to the basal and lower levels of the ductal papillomas similar to normal control oral epithelium but in the majority of papillary SCCA, staining of CD44 extended throughout the entire thickness of the lesion. The level of staining intensity of the papillary SCCA in this study was more compatible with that reported by Bahar et al for oral squamous papillomas than that reported for most types of invasive carcinoma in the sinonasal and breast locations previously studied as well [1][2][3][4][5]. No prior studies evaluating the expression of CD44 in papillary SCCA as compared to other variants of oral SCCA could be found in a search of the literature.…”

“…It has been shown to be universally present in sinonasal ductal papillomas but lose expression when invasive squamous cell carcinoma (SCCA) arises in these lesions [1]. Similar results have been shown comparing intraductal breast papillomas to invasive papillary carcinoma [2][3][4].It has also been demonstrated to be downregulated in oral dysplasia and SCCA when compared to normal oral epithelium, epithelial hyperplasia, and oral squamous papillomas [5].…”

“…Ingle et al evaluated 76 cases of sinonasal inverted papillomas (SIP), 2 cases of SIP with carcinomain situ, and 10 cases of SIP with frank invasive SCCA [1]. They found that 100 % of the SIP and the SIP with carcinoma-in situ were positive for the stain, while a loss of CD44 expression was found in the SIP with SCCA group (60 % negative, 40 % weakly positive) [1]. They concluded that for SCCA arising in SIP, loss of CD44 was associated with carcinoma development [1].…”

“…They found that 100 % of the SIP and the SIP with carcinoma-in situ were positive for the stain, while a loss of CD44 expression was found in the SIP with SCCA group (60 % negative, 40 % weakly positive) [1]. They concluded that for SCCA arising in SIP, loss of CD44 was associated with carcinoma development [1].…”

Bilateral inverted papilloma: A report of two cases and review of the current literature

“…The factors which are responsible for this malignant transformation are as yet not understood. A number of studies have been performed in an attempt to discover predictive characteristics for malignant change [28,29]. Eggers et al [28] studied 93 cases of inverted papilloma with regards to both patient and tumor characteristics.…”