SMARCB1 deficient sinonasal carcinoma: An emerging entity with a diagnostic challenge.

SMARCB1 deficient sinonasal carcinomas are rare neoplasms, classified under sinonasal undifferentiated carcinomas by the fourth edition of the World Health Organization (WHO) classification of head and neck tumors. It is characterized immunohistochemically by loss of SMARCB1(INI1) expression. We are reporting the case of a 63-year-old man who was evaluated for nasal stuffiness of 3 months duration in another hospital where a radiological evaluation showed a polypoidal soft tissue lesion in the right maxillary sinus extending to the right nasal cavity and spheno-ethmoidal sinus. He underwent excision biopsy which was reported as non- keratinizing nasopharyngeal carcinoma. He was referred to our center with residual disease in spheno-ethmoidal recess for which radiotherapy was given. After completion of radiotherapy, the primary site had no residual disease, but while on follow-up he developed left sided neck nodes within 4 months of completion of treatment. Excision of the lesion was done and histopathological and immunohistochemical analysis revealed it to be metastasis from SMARCB1 deficient sinonasal carcinoma and not nasopharyngeal carcinoma as diagnosed from the other center. This case is being reported to highlight the diagnostic challenge associated with this rare entity.

Myoepithelial carcinoma with rhabdoid features in the maxillary sinus: Immunohistochemical and in situ hybridization analysis of a rare case.

Myoepithelial carcinomas of the head and neck are often located in the major salivary glands, notably in the parotid glands, being less frequent in the minor salivary glands. Noteworthy, myoepithelial carcinoma in the maxillary sinus is extremely rare. In fact, only five cases have been previously published to date. Here, we present, for the first time, a detailed immunohistochemical and in situ hybridization analysis of a SMARCB1 (INI-1)-intact myoepithelial carcinoma with rhabdoid features, expanding the histopathological spectrum of high-grade sinonasal carcinomas.

Sinonasal SMARCB1 (INI1) Deficient Carcinoma With Yolk Sac Tumor Differentiation: Report of a Case and Comparison With INI1 Expression in Gonadal Germ Cell Tumors.

SMARCB1 (INI1) deficient sinonasal carcinoma is a recently recognized entity with wide histomorphologic spectrum. We present a case of this carcinoma that contained, in addition to a "common" morphology, scattered foci of yolk sac tumor differentiation. The tumor occurred in paranasal sinuses in a 44-year-old woman. Immunohistochemically, it was diffusely negative for INI1, whereas an expression of yolk sac tumor markers (α-fetoprotein, glypican-3, CDX2) was limited to the yolk sac tumor component. For comparison with the present case, we performed INI1 immunostaining on a series of 11 gonadal germ cell tumors with yolk sac tumor differentiation. All of these cases showed strong and diffuse expression of INI1, in contrast with the present sinonasal tumor. Our findings expand the morphologic spectrum of SMARCB1 (INI1) deficient sinonasal carcinoma. In addition, we show preliminarily that gonadal germ cell tumors with yolk sac tumor differentiation are not SMARCB1/INI1-deficient.

SMARCB1/INI1-deficient sinonasal carcinoma shows methylation of RASSF1 gene: A clinicopathological, immunohistochemical and molecular genetic study of a recently described entity.

The aim of the study was detailed clinicopathological investigation of SMARCB1/INI1-deficient sinonasal carcinomas, including molecular genetic analysis of mutational status and DNA methylation of selected protooncogenes and tumor suppressor genes by means of next generation sequencing (NGS) and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). A total of 4/56 (7%) cases of SMARCB1/INI1-deficient carcinomas were detected among 56 sinonasal carcinomas diagnosed over a 19year period using immunohistochemical screening. The series comprised 3 males and 1 female, aged 27-76 years (median 64 years). All tumors arose in the nasal cavity. Three neoplasms were diagnosed in advanced stage pT4. During the follow-up period (range 14-111 months (median 72 months)), three tumors recurred locally, but none of the patients developed regional or distant metastases. Ultimately, two patients died due to the tumor. Microscopically, all tumors consisted of infiltrating nests of polygonal basaloid cells with a variable component of rhabdoid cells with eosinophilic cytoplasm. Immunohistochemically, there was almost diffuse expression of cytokeratins (CK), p16, p40 and p63 in all cases, while expression of CK5/6, CK7 and vimentin was only focal or absent. The detection of NUT gave negative results. In three cases, the absence of SMARCB1/INI1 expression was due to deletion of SMARCB1/INI1 gene. Methylation of SMARCB1/INI1 gene was not found. One tumor harbored HPV18 E6/E7 mRNA. All 12 genes (BRAF, BRCA1, BRCA2, KIT, EGFR, KRAS, NRAS, PDGFRA, PIK3CA, PTEN, RET, and ROS1) tested for mutations using NGS were wild-type. Regarding DNA methylation, all four SMARCB1/INI1-deficient tumors showed methylation of RASSF1 gene by means of MS-MLPA. There was a statistically significant difference in RASSF1 gene methylation between SMARCB1/INI1-deficient and SMARCB1/INI1-positive tumors (p=0.0095). All other examined genes (ATM, BRCA1, BRCA2, CADM1, CASP8, CD44, CDKN1B, CDKN2A, CDKN2B, CHFR, DAPK1, ESR1, FHIT, GSTP1, HIC1, KLLN, MLH1a, MLH1b, RARB, and VLH) were unmethylated. In summary, we described four cases of SMARCB1/INI1-deficient sinonasal carcinoma with detailed clinicopathological data indicating that these tumors can be regarded as a distinct entity with aggressive behaviour. For the first time, we performed analysis of DNA methylation in SMARCB1/INI1-deficient sinonasal carcinomas, reporting on significantly higher methylation of RASSF1 gene in this neoplasm.

Immunohistochemical Study EMT-Related Proteins in HPV-, and EBV-Negative Patients with Sinonasal Tumours.

Epithelial to mesenchymal transition (EMT) is a biological process in which the epithelial cells, transform to mesenchymal cells via multiple biochemical modifications. Immunohistochemical method was used to examine the expression of EMT-related proteins: Slug, E-cadherin and fibronectin, in 41 cases of sinonasal inverted papilloma (SIP), 33 cases of sinonasal squamous cell carcinoma (SNC), and 22 cases of normal mucosa as a control. In all cases negative viral status was previously confirmed using both in situ hybridization and immunohistochemical method. The immunoexpression of Slug and fibronectin were significantly increased in the SNC group as compared to SIPs and control cases. The immunoexpresssion of Slug was also higher in SIPs as compared to controls. The immunoexpression of E-cadherin was significantly lower in SNCs group as compared with SIPs and controls, but no statistically significant difference in E-cadherin immunoexpression was noted between SIPs and control cases. There were statistically significant negative correlations between immunoexpression of Slug vs E-cadherin, E-cadherin vs fibronectin and positive correlation between Slug vs fibronectin in SNC. Statistically significant correlation between Slug and fibronectin immunoexpression in SIPs was also found. In conclusion, our findings suggest that relationships between Slug, E-cadherin and fibronectin could potentially point to EMT in the sinonasal cancer. Lack of correlation between EMT-related proteins in tested SIPs could reflect a benign nature of those cases.

Human epidermal growth factor receptor 2/neu as a novel therapeutic target in sinonasal undifferentiated carcinoma.

BACKGROUND: Sinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive cancer. Despite multimodal therapy, the prognosis in SNUC remains poor, and new therapies are needed. Thus, the purpose of this study was to explore potential therapeutic targets in SNUC. METHODS: Using the human-derived SNUC MDA8788-6 cell line, we performed whole genome single nucleotide polymorphism (SNP) analysis to identify copy number changes in this line. Protein expression levels were evaluated by Western blotting. Cell growth inhibition was assessed by methylthiazol tetrazolium (MTT) and clonogenic assays. The mouse flank model was used to examine the effect of growth inhibition in vivo. RESULTS: The ERBB2 gene was highly amplified and cell extracts showed human epidermal growth factor receptor 2 (HER2) was overexpressed and phosphorylated in MDA8788-6. Lapatinib effectively inhibited the HER2 signaling pathway in our SNUC cell line. HER2 inhibition successfully suppressed the cell growth of MDA8788-6 cells both in vitro and in vivo. CONCLUSION: Targeting HER2 may be a promising avenue for the development of novel therapies for SNUC. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1926-E1934, 2016.

Primary mucosal melanoma of the sinonasal tract: a clinicopathologic and immunohistochemical study of thirty-two cases.

Sinonasal mucosal melanoma is a rare disease with poor survival. These tumors may have associated intraepithelial melanocytic proliferations, which are not extensively characterized. This retrospective analysis of 32 patients with sinonasal mucosal melanoma examined associated intraepithelial melanocytic proliferations in the context of diagnostic and prognostic features. Patient age ranged from 30 to 90 years (median 71) with a male to female ratio of approximately 3:2. Follow up for 31 patients ranged from 5 to 211 months (mean 42 months). Most patients died from melanoma-associated causes (18/31, 58 %), six (19 %) died from unknown causes, two (6 %) were alive with metastatic disease, and only five patients (16 %) remained alive without melanoma. The tumors were histopathologically heterogeneous, displaying epithelioid, spindled, and small cell cytomorphology. The presence of >2 mitoses/mm(2) and necrosis correlated with tumor progression and overall survival, respectively (p = 0.04 for both). Melanoma in situ, defined as a confluent intraepithelial proliferation of cytologically atypical melanocytes, was identified in 20 of 30 evaluable cases (67 %) and confirmed with immunohistochemical staining for microphthalmia-associated transcription factor. Melanocytic hyperplasia, defined as intraepithelial melanocytic proliferation without confluent growth or marked atypia, was seen in five cases (16 %). This incidence of associated intraepithelial melanocytic proliferations (83 %) is higher than previously reported. Because of the locally aggressive nature of these tumors, an awareness of the high rate of associated intraepithelial melanocytic proliferations may inform future studies of therapeutic options.

Mesenchymal phosphaturic tumour: early detection of recurrence.

The case of a recurrent phosphaturic mesenchymal tumour of the maxillary sinus 10 years after the first surgical excision is reported. The neoplasm first presented with paraneoplastic osteomalacia causing a pathological femur fracture. A right maxillary sinus tumour was identified and treated thereafter. The patient had no local symptoms and serum electrolytes returned to normal after surgical removal of the tumour. However, 10 years later, the patient's urine Ca and P levels increased and an octreoscan detected a new tumour in the right maxillary sinus. Early diagnosis prevented the effects of the paraneoplastic activity of the neoplasm. This case emphasises the importance of specific, close follow-up, because the neoplasm rarely produces local signs indicating its position. To our knowledge, this is the first reported case of a late relapse presenting without relevant symptoms (local pain or swelling or pathological fractures).

Prognostic value of osteopontin in patients treated with primary radiotherapy for head and neck cancer.

BACKGROUND: The prognostic value of tumor osteopontin (OPN) in patients with squamous-cell head and neck cancer (SCHNC) was investigated. MATERIALS AND METHODS: OPN expression was assessed by immunohistochemical methods in 50 patients, who were treated with primary radiotherapy (RT) for locally advanced SCHNC. The effects of OPN on clinical parameters, local-regional control after RT and metastasis-free survival, was assessed. RESULTS: The rate of OPN expression in tumor tissue was 76%. OPN positive cases had lower Hb levels (p=0.088). Mean time to local recurrence was 53.8 months (SE 3.9) in OPN-negative cases and 39.1 months (SE 4.7) in OPN-positive cases (p=0.047). OPN increased the risk of local recurrence 5.9 times (p=0.085). It had no effect on metastasis-free (p=0.116) or overall survival (p=0.123). OPN was positive in 12 of 19 cases that developed grade 3-4 acute radiation dermatitis (p=0.096). CONCLUSIONS: OPN expression is associated with an increase in local recurrence in patients who were treated with primary RT for locally advanced SCHNC.

[High-grade transformation in adenoid cystic carcinoma: a clinicopathologic study].

OBJECTIVE: To study the clinicopathologic features and possible molecular mechanisms of adenoid cystic carcinoma with high-grade transformation. METHODS: Four cases of adenoid cystic carcinoma with high-grade transformation were enrolled into the study. Immunohistochemical study for smooth muscle actin, p63, p53 and Ki-67 was carried out. C-myc gene status was analyzed by fluorescence in-situ hybridization. RESULTS: There were altogether 3 males and 1 female. The mean age of the patients was 55.5 years. Two patients died 17 months and 29 months after operation, respectively. One patient had distant metastasis 23 months after operation and was still alive at 26-month follow up. The remaining patient remained tumor free at 3-month follow up. High-grade transformation in adenoid cystic carcinoma presented either as poorly differentiated adenocarcinoma or undifferentiated carcinoma. Histologic examination showed sheets of pleomorphic tumor cells occupying more than one low-power field. The high-grade carcinoma cells showed increased nuclear-cytoplasmic ratio, prominent eosinophilic nucleoli and active mitosis (ranging from 8 to 25 per high-power field). Comedo necrosis was observed in 2 cases and multiple foci of calcifications in 3 cases. Immunohistochemical study demonstrated loss of myoepithelial differentiation, overexpression of p53 and high proliferative index by Ki-67. No c-myc translocation or copy-number changes were observed. CONCLUSIONS: High-grade transformation in adenoid cystic carcinoma is rare. The histopathologic features are rather distinctive and the biologic behavior is aggressive. C-myc gene mutation does not seem to play a key role in the pathogenesis.

Tumour-suppressive microRNA-874 contributes to cell proliferation through targeting of histone deacetylase 1 in head and neck squamous cell carcinoma.

BACKGROUND: Our recent studies of microRNA (miRNA) expression signature demonstrated that microRNA-874 (miR-874) was significantly downregulated in maxillary sinus squamous cell carcinoma (MSSCC), and a putative tumour-suppressive miRNA in human cancers. Our aim of this study was to investigate the functional significance of miR-874 in cancer cells and to identify novel miR-874-mediated cancer pathways and responsible genes in head and neck squamous cell carcinoma (HNSCC). METHODS: Gain-of-function studies using mature miR-874 were performed to investigate cell proliferation and cell cycle distribution in HNSCC cell lines (SAS and FaDu). To identify miR-874-mediated molecular pathways and targets, we utilised gene expression analysis and in silico database analysis. Loss-of-function assays were performed to investigate the functional significance of miR-874 target genes. RESULTS: Expression levels of miR-874 were significantly downregulated in HNSCC tissues (including oral, pharyngeal and laryngeal SCCs) compared with normal counterpart epithelia. Restoration of miR-874 in SAS and FaDu cell lines revealed significant inhibition of cell proliferation and induction of G2/M arrest and cell apoptosis. Our expression data and in silico analysis demonstrated that miR-874 modulated the cell cycle pathway. Moreover, histone deacetylase 1 (HDAC1) was a candidate target of miR-874 regulation. Luciferase reporter assays showed that miR-874 directly regulated HDAC1. Silencing of the HDAC1 gene significantly inhibited cell proliferation and induced G2/M arrest and cell apoptosis in SAS cells. CONCLUSIONS: Downregulation of miR-874 was a frequent event in HNSCC. miR-874 acted as a tumour suppressor and directly targeted HDAC1. Recognition of tumour-suppressive miRNA-mediated cancer pathways provides new insights into the potential mechanisms of HNSCC oncogenesis and suggests novel therapeutic strategies for the disease.

Sinonasal undifferentiated carcinoma: morphological heterogeneity, diagnosis, management and biological markers.

Sinonasal undifferentiated carcinoma is a highly aggressive lesion arising in the superior nasal cavity and paranasal sinuses. Differential diagnosis is wide because a range of similar lesions can present at this site. There is increasing evidence that sinonasal undifferentiated carcinoma is a surface (Schneiderian) epithelial-derived malignancy, with or without concurrent neuroendocrine differentiation. Prognosis is poor; recurrence with metastasis to lymph nodes and distant sites is frequent. A combination of radical surgery, chemotherapy and radiotherapy appears to provide the best chance of survival.

Sinonasal undifferentiated carcinoma (SNUC): morphoproteomic-guided treatment paradigm with clinical efficacy.

Sinonasal undifferentiated carcinoma (SNUC) is a rare and highly malignant tumor that occurs in the nasal cavity and/or paranasal sinuses. Prognosis is poor despite multimodality treatment. Currently, there is no optimal standard of treatment, partially due to a lack of research defining the biology of such tumors. This report discusses two SNUC cases where patients received a novel chemotherapeutic approach using cisplatin, etoposide, Adriamycin (doxorubicin), metformin, and adjuvant melatonin therapies based on morphoproteomic-guidance, followed by consolidation with chemoradiation therapy. This resulted in excellent and objective tomographic and magnetic resonance imaging and clinical responses including complete responses in the induction phase utilizing morphoproteomic-guided therapies. Later, endoscopic excision of the tumor bed failed to reveal any residual tumor. Morphoproteomics helped to define the biology of these SNUC tumors and provided targets for the agents employed, creating a new treatment paradigm for such tumors. This treatment regimen poses a new effective regimen to treat SNUC.

[Utility of NUT gene expression and rearrangement in diagnosis of NUT midline carcinoma in upper respiratory tract].

OBJECTIVE: To investigate the importance of expression of the NUT gene and its rearrangement in diagnosing NUT midline carcinoma (NMC) of the upper respiratory tract; and to evaluate the prevalence, histological features and differential diagnosis of NMC of the upper respiratory tract. METHODS: One-hundred and sixty-three small cell malignant tumors of the upper respiratory tract were reviewed at the Beijing Tongren Hospital, Capital Medical University over a 20-year period. These cases included poorly-differentiated squamous cell carcinomas (n = 31), undifferentiated carcinoma (n = 1), non-keratizing undifferentiated nasopharyneal carcinomas (n = 60), small cell neuroendocrine carcinomas (n = 6) and non-epithelial small round cell malignant tumors (n = 65). The clinical and pathologic features were investigated. All cases were subjected to Epstein-Barr virus encoded RNA (EBER) in situ hybridization and NUT monoclonal antibody immunohistochemical staining. Cases positive for NUT immunohistochemistry and negative for EBER in situ hybridization were submitted for fluorescent in situ hybridization (FISH) for rearrangements in both BRD4 and NUT genes, and immunohistochemical staining for a set of cytokeratins (AE1/AE3, CK7, CK8), p63,and neuroendocrine markers (NSE, Syn, CgA, S-100 protein, CD56). RESULTS: Three cases of poorly-differentiated squamous cell carcinomas and one case of undifferentiated carcinoma showed diffuse nuclear immunohistochemical staining with antibody against NUT. These positive cases approximately accounted for 12.5% (4/32) of this group, 4.1% (4/98) of the malignant epithelial carcinomas and 2.5% (4/163) of all small round cell malignant tumors in the study. The age of these patients were 42 - 59 years. Other groups were all negative for NUT immunohistochemistry. These four cases also stained for antibodies against cytokeratins and p63, but were negative for neuroendocrine markers and not associated with EBV infection. Only two of these four cases showed rearrangements of the NUT and BRD4 genes by FISH. These two patients died within one year. The other two patients that did not demonstrate NUT rearrangement by FISH were alive and did not have an aggressive clinical course, surviving 40 and 12 months respectively. CONCLUSIONS: NMC is a rare small round cell malignant tumor in the upper respiratory tract. Only in the groups of primary poorly differentiated squamous cell carcinoma and undifferentiated carcinoma were positive for NUT immunohistochemical staining and NUT rearrangement by FISH. NMC typically occurs in midline organs, and affects the sinonasal tract. It is not associated with EBV infection. There is difference in the clinical course and prognosis among NMC patients. NUT immunohistochemical staining and NUT gene rearrangement analysis can differentiate NMC from other small cell tumors in the upper respiratory tract.

NUT midline carcinomas of the sinonasal tract.

NUT midline carcinoma (NMC) is a highly lethal tumor defined by translocations involving the NUT gene on chromosome 15q14. NMC involves midline structures including the sinonasal tract, but its overall incidence at this midline site and its full morphologic profile are largely unknown because sinonasal tumors are not routinely tested for the NUT gene translocation. The recent availability of an immunohistochemical probe for the NUT protein now permits a more complete characterization of sinonasal NMCs. The archival files of The Johns Hopkins Hospital Surgical Pathology were searched for all cases of primary sinonasal carcinomas diagnosed from 1995 to 2011. Tissue microarrays were constructed, and NUT immunohistochemical analysis was performed. All NUT-positive cases underwent a more detailed microscopic and immunohistochemical analysis. Among 151 primary sinonasal carcinomas, only 3 (2%) were NUT positive. NUT positivity was detected in 2 of 13 (15%) carcinomas diagnosed as sinonasal undifferentiated carcinoma and in 1 of 87 (1%) carcinomas diagnosed as squamous cell carcinoma. All occurred in men (26, 33, and 48 y of age). The NMCs grew as nests and sheets of cells with a high mitotic rate and extensive necrosis. Two were entirely undifferentiated, and 1 tumor showed abrupt areas of squamous differentiation. Each case had areas of cell spindling, and 2 were heavily infiltrated by neutrophils. Immunohistochemical staining was observed for cytokeratins (3 of 3), epithelial membrane antigen (3 of 3), p63 (2 of 3), CD34 (1 of 3), and synaptophysin (1 of 3). All patients died of the disease (survival time range, 8 to 16 mo; mean, 12 mo) despite combined surgery and chemoradiation. NMC represents a rare form of primary sinonasal carcinoma, but its incidence is significantly increased in those carcinomas that exhibit an undifferentiated component. Indiscriminant analysis for evidence of the NUT translocation is unwarranted. Instead, NUT analysis can be restricted to those carcinomas that demonstrate undifferentiated areas. The availability of an immunohistochemical probe has greatly facilitated this analysis and is helping to define the full demographic, morphologic, and immunohistochemical spectrum of sinonasal NMC.

Expression of p16 in sinonasal undifferentiated carcinoma (SNUC) without associated human papillomavirus (HPV).

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.

A histologic and immunohistochemical study describing the diversity of tumors classified as sinonasal high-grade nonintestinal adenocarcinomas.

Nonintestinal sinonasal adenocarcinomas (SNACs) are somewhat poorly characterized and high-grade nonintestinal SNACs have been only rarely reported. Here, we review our experience with these tumors. Twenty-seven cases of high-grade nonintestinal SNACs were identified from 22 men and 5 women. Ages ranged from 22 to 83 years (mean±1 standard deviation=54.7±18.6 y; median=60 y). Thirteen cases involved the nasal cavity and sinuses, 10 involved the nasal cavity only, and 4 involved sinuses only. Most cases had marked cytologic and nuclear pleomorphism, abundant mitotic activity, and necrosis; however, these features were not uniform. Although histologically heterogeneous, recurrent growth patterns were seen that resembled other neoplasms of the area. Tumors lacked CDX2 and CK20 immunoreactivity (aside from rare CK20 immunoreactive cells). High-grade nonintestinal SNACs are more common in men and, although they occur over a wide age range, they are much more common in older individuals. Histologically, they show a great deal of heterogeneity.

Identification of novel molecular targets regulated by tumor suppressive miR-1/miR-133a in maxillary sinus squamous cell carcinoma.

Based on our microRNA (miRNA) expression signature analysis of maxillary sinus squamous cell carcinoma (MSSCC), we found that miR-1 and miR-133a were significantly reduced in tumor tissues. Quantitative real-time RT-PCR revealed that the expression levels of miR-1 and miR-133a were significantly downregulated in clinical MSSCC tumor tissues compared with normal tissues. We focused on the functional significance of miR-1 and miR-133a in cancer cells and identification of the novel cancer networks regulated by these miRNAs in MSSCC. Restoration of downregulated miRNAs (miR-1 or miR-133a) in cancer cells revealed that both miRNAs significantly inhibited cancer cell proliferation and induced cell apoptosis. Molecular target identification of these miRNAs showed that transgelin 2 (TAGLN2) and purine nucleoside phosphorylase (PNP) were regulated by miR-1 and miR-133a. Both TAGLN2 and PNP mRNA expression levels were significantly upregulated in clinical MSSCC tumor tissues. Silencing studies of target genes demonstrated that both genes inhibited cancer cell proliferation. The identification of novel miR-1/miR-133a-regulated cancer pathways could provide new insights into potential molecular mechanisms of MSSCC oncogenesis.

Anaplastic myoepithelial carcinoma of the sinonasal tract: an underrecognized salivary-type tumor among the sinonasal small round blue cell malignancies? Report of one case and a review of the literature.

We present a 45 year old female patient with a nasal carcinoma showing high-grade/anaplastic histomorphological features and with a distinct myoepithelial immunohistochemical phenotype including positivity for smooth muscle actin, p63, S100 protein with no sustentacular pattern, calponin, cytokeratin 14, vimentin and cytokeratins (AE1-3 and CK5/6). A minority (<5%) of the cells showed focal and variable immunoreactivity for EMA with no cuticular/canalicular pattern. Bcl-2, CD99, CD117 and CD56 were variously positive, but chromogranin and synaptophysin were negative. Weak to moderate nuclear p53 immunoreactivity was seen in 50% of tumor cells. Mib-1/Ki-67 showed an average proliferation of 60-70%. Fluorescent in situ hybridization revealed no EWS-gene translocation. In situ hybridization for EBER was negative.