Squamous Cell Carcinoma Of Maxillary Sinus Research Articles

Maxillary sinus squamous cell carcinoma during pregnancy: a new case report

Less than one percent of malignant lesions are malignant tumors of the paranasal sinuses. The majority of maxillary sinus carcinomas are squamous cell carcinomas (SCC). There are few reports of head and neck SCC found during pregnancy; however, in this article, a 23-year-old woman in the fourth month of pregnancy was diagnosed with a maxillary sinus SCC. The histopathologic evaluation of the lesion showed a malignant proliferation of squamous cells with a sheath and cord formation that invaded the surrounding tissue. These findings were compatible with SCC. Hemimaxillectomy, neck dissection, and chemoradiotherapy were conducted; however, despite these therapeutic interventions, the patient died 11 months after the initial visit due to distant metastasis.

Squamous cell carcinoma of the maxillary sinus: A population-based analysis.

Squamous cell carcinoma (SCC) accounts for > 90% of head and neck cancers and 60% to 75% of malignancies of the paranasal sinuses. The most commonly affected paranasal sinus is the maxillary. Epidemiologic, incidence, and survival trends have been studied for maxillary sinus SCC (MSSCC), but far less is known about its metastatic potential. Retrospective database analysis. The Surveillance, Epidemiology, and End Results database was used to extract frequency, incidence, and survival data for MSSCC between 2004 and 2012. The resultant cases were stratified according to patient demographics and collaborative stage information, including extent of disease, lymph node involvement, TNM staging, and regional and distant metastasis. A total of 854 cases of MSSCC were identified. The mean age at diagnosis was 66.6 years, with 87.4% presenting at > 50 years. Most patients (65.1%) were male. Whites accounted for 74.6% of cases. A majority (64.3%) of cases presented with stage IV disease. Overall 5-year disease-specific survival was 23.4%. Neck involvement was seen in 7.6% of T1 tumors, 22.2% of T2 tumors, 18.5% of T3 tumors, and 12.2% of T4 tumors. Distant metastasis was not seen in T1-T3 tumors, but was present in 6.8% of T4 tumors. MSSCC is a rare entity with poor overall prognosis. The majority of patients included in this study were white males aged ≥50 years, with most tumors presenting at advanced stages. Nodal involvement and distant metastasis are poor prognostic indicators. T1-T3 tumors did not metastasize to distant sites. 4.

Features of morphological variants of squamous cell carcinoma of the maxillary sinus: immunohistochemical characteristic.

Background. The feature of malignant tumours in maxillary sinus is a late appeal of patients (T3-T4), as a result of the absence of pain and minor clinical manifestations, it requires large amounts of surgical interventions and leads to disability. Objective. The article analyzes the morphological variants of maxillary sinus squamous cell carcinoma (SCC) with their immunohistochemical characteristic. Methods. In the study we analyzed the original biopsy material from 37 patients with maxillary sinus cancer T3-4N0-1M0 (31 men and 6 women) aged from 37 to 71 years with histologically confirmed diagnosis of SCC for 2010-2014. The primary monoclonal antibodies CK HMW (clone AE3), p63 (clone 4A4), р16INK4 (clone DCS 240) were used. Results. Analyzing the distribution of various forms of maxillary sinus SCC, it was found that the typical forms of SCC are found in most of cases, 29 of 37 (78.4%), compared with specific morphological forms that accounted for just 21.6%. Conclusions. Due to the expression of the marker CK HMW it was found that in typical forms of SCC and in some special morphological forms (spindle cell carcinoma and verrucous carcinoma) with decreasing degree of squamous cell differentiation, the level of the expression of CK HMW also decreases (p<0,001, r = 0.861; p <0,001, r = 0,638). It is an indicator of poor prognosis, but aggressive behavior of basaloid SCC and adenosquamous carcinoma do not depend on the presence or absence of CK HMW. High expression of marker p63 (average level 92,5±3,67%) is a key-point of verification of basaloid SCC. Lack of positive reaction with the marker of viral lesions p16INK4 in forms with keratinization confirms the idea of different etiologic factors and ways of carcinogenesis of typical forms of SCC.

P12.09 * MALIGNANT TUMORS OF ANTERIOR SKULL BASE: IS THE ROLE OF SURGERY ENHANCED IN THE ENDOSCOPY ERA?

INTRODUCTION: Malignant tumors of anterior skull base represent a surgical challenge because of their anatomical location, the necessity of achieving negative margins, and the often-cosmetically disfiguring transfacial approaches needed. Recently, expanded endonasal endoscopic approaches (EEEA) have been developed, either alone or combined with transcranial approaches for treatment of these malignant lesions. We report our experience to illustrate the relative safety and effectiveness of the EEEA for skull base malignancies alone or combined when possible with minimally invasive approaches or traditional surgery. METHODS: From June 2009, 13 patients harbouring malignant neoplastic lesions of anterior skull base were treated at our department. Four patients affected by sinonasal malignancies with extension in anterior cranial fossa underwent to combined open subfrontal or minimally invasive supra orbital approach and EEEA. In 2 patients with respectively esthesioneuroblastoma and maxillary sinus squamous cell carcinoma a combined supraorbital key-hole craniotomy and EEEA were perfomed. Seven clival metastases with VI cranial nerve palsy were approached by the EEEA supplemented by neuronavigation. RESULTS: Gross total removal was performed in 9 out of 13 patients. In the other cases partial resection, but with adequate decompression and diagnosis were achieved. There were no mortality, 1 patient had infection and 1 deep vein thrombosis. CONCLUSIONS: In our experience EEEA are an integral part of the neurosurgical armamentarium for the treatment of the skull base malignancies. In properly selected cases, it affords similar oncologic outcomes with lower morbidity than traditional open approaches. The major potential advantage of the EEEA approach is direct “natural” anatomical route to the lesion without traversing any major neurovascular structures, so obviating brain retraction. Many tumors grow in a medial-to-lateral direction, displacing structures laterally as they expand, creating natural corridors for their resection via an antero-medial approach. The complementary information provided by endoscopy can assist the surgeon in safely extend the approach maximizing the extent of resection and decompression in hidden angles. Nonetheless, these minimal access approaches should be considered a complement to well-established open approaches, which are still necessary in most advanced tumors.

Multi‐institutional retrospective study for the evaluation of ocular function–preservation rates in maxillary sinus squamous cell carcinomas with orbital invasion

The purpose of this retrospective analysis was to evaluate ocular function and survival rates among treatment modalities in patients with maxillary sinus cancer with orbital invasion. Eighty-seven patients were classified according to the main treatment modality. Ocular function preservation rates and survival rates were evaluated for each therapeutic modality. The 5-year overall survival rate for the en bloc resection, conservative surgery, superselective intra-arterial chemotherapy, and radiotherapy (RADPLAT), intravenous chemoradiotherapy (IV-CRT) was 70%, 35%, 49%, and 31%, respectively. The ocular function preservation rate for each group was 15%, 27%, 30%, and 17%, respectively. In the en bloc resection group, there was no significant difference in the 5-year overall survival rate between patients with orbital exenteration and those without orbital exenteration (72% vs 71%; p = .9321). The en bloc resection group showed a favorable survival rate but a low preservation rate. Preservation of orbital contents did not reduce the survival rate.

Lymph Node Metastasis in T4 Maxillary Sinus Squamous Cell Carcinoma: Incidence and Treatment Outcome

The purpose of this study was to evaluate the incidence of lymph node metastasis among patients with T4 maxillary sinus squamous cell carcinoma (MS-SCC) as well as the delayed metastasis rate and the treatment outcome for untreated N0 neck in patients with T4 MS-SCC. Consecutive series of all patients (n = 128) with previously untreated T4 maxillary sinus SCC between 2006 and 2007 were obtained from 28 institutions belonging to or cooperating in the Head and Neck Cancer Study Group of the Japan Clinical Oncology Group. Of the 128 patients, 28 (21.9 %) had lymph node metastasis, and six patients (4.7 %) had distant metastasis at diagnosis. Among the 111 patients who were treated with curative intent, 98 had clinically N0 neck disease and did not receive prophylactic neck irradiation. A total of 11 patients (11.2 %) subsequently developed evidence of lymph node metastasis, of whom eight were among the 83 patients with an N0 neck and had not received elective neck treatment. There were 15 patients who received an elective neck dissection as part of the initial treatment, of whom three had pathologically positive for lymph node metastases. Of 11 patients, six patients with nonlateral retropharyngeal lymph node metastasis without primary or distant disease were successfully salvaged. This study identified the incidence of lymph node metastasis among patients with T4 MS-SCC as well as the delayed metastasis rate and the treatment outcome for untreated N0 neck in patients with T4 MS-SCC. These results will be of assistance in selecting treatment strategy for T4 MS-SCC in the future.

The incidence of late neck recurrence in N0 maxillary sinus squamous cell carcinomas after superselective intra-arterial chemoradiotherapy without prophylactic neck irradiation

The efficacy of elective neck irradiation (ENI) for patients with N0 carcinoma of the maxillary sinus has been controversial. The purpose of our study was to investigate the incidence of late neck recurrence and the mortality rate from regional disease in patients with N0 maxillary sinus cancer after superselective cisplatin infusion and concomitant radiotherapy (RADPLAT) without ENI. We retrospectively analyzed 48 patients with N0 maxillary sinus cancer who underwent RADPLAT. Chemotherapy consisted of 100-120 mg/m(2) superselective intra-arterial cisplatin administered at a median rate of four times weekly. Concurrent radiation therapy was administered at a median dose of 65 Gy without ENI. Late neck recurrence was observed in 8.3% (4/48). Three patients underwent salvage neck dissection and survived without any evidence of disease. The remaining patient did not undergo neck dissection due to coexistence with distant metastasis, and he died of regional disease. The mortality rate from regional disease was calculated to be 2% (1/48). The incidence of late neck recurrence was not frequent, and the mortality rate from regional disease was low. Salvage neck dissection was considered to be feasible for patients with late neck recurrence. When definitive radiotherapy and concomitant chemotherapy are applied, it is considered that ENI is not required for cases of N0 maxillary sinus cancer.

Superselective intra-arterial cisplatin infusion and concomitant radiotherapy for maxillary sinus cancer

Background:The purpose of this study was to evaluate the efficacy of superselective cisplatin infusion with concomitant radiotherapy (RADPLAT) for previously untreated patients with the squamous cell carcinoma of maxillary sinus (SCC-MS).Methods:Between 1999 and 2010, 54 patients were given superselective intra-arterial infusions of cisplatin (100–120 mg m−2 per week) with simultaneous intra-venous infusions of thiosulfate to neutralise cisplatin toxicity and conventional radiotherapy (65–70 Gy).Results:One patient (1.9%) was diagnosed with T2, 14 (25.9%) with T3, 27 (50%) with T4a, and 12 (22.2%) with T4b disease. Lymph-node involvement was present in 12 patients (22.2%). During the median follow-up period of 6.4 years, the 5-year local progression-free and overall survival rates were 65.8 and 67.9% for all patients, respectively. No patient died as a result of treatment toxicity or experienced a cerebrovascular accident. Osteonecrosis (n=5), brain necrosis (n=1), and ocular/visual problems (n=14) were observed as late adverse reactions.Conclusion:We have shown excellent overall survival and local progression-free rate in SCC-MS patients treated by RADPLAT with acceptable rates of acute and late toxicity. A multi-institutional trial is needed to prove that this strategy is a feasible and effective approach for the treatment of SCC-MS.

Abstract 4182: microRNA-29 family as tumor suppressive microRNAs in head and neck squamous cell carcinoma: microRNA-29a/b/c inhibits cell migration and invasion targeting focal adhesion and ECM pathways.

Abstract BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. In spite of considerable advances in multimodality therapy such as surgery, radiation therapy and chemotherapy, the overall five-year survival rate for patients with HNSCC is around 40%. Understanding of the molecular cancer pathway underlying HNSCC could significantly improve diagnosis, therapy, and disease prevention. Our microRNA (miRNA) expression signatures of hypopharyngeal squamous cell carcinoma (SCC), and maxillary sinus SCC revealed that the expression of microRNA-29 family (miR-29a/b/c) was significantly reduced in cancer tissues. The aim of the study was to investigate the functional significance of miR-29a/b/c and to explore the novel molecular pathways and responsibility genes regulated by miR-29a/b/c in HNSCC. METHODS: Gain-of-function studies were performed to investigate cancer cell proliferation, migration and invasion by mature miRNAs transfection into HNSCC cell lines (SAS and FaDu). To identify the biological processes or pathways potentially regulated by the miR-29 family, we applied genome-wide gene expression analysis and in silico study; TargetScan database [http://www.targetscan.org/] and GENECODIS software, which assigned a number of the putative miRNA targets to known pathways in KEGG [http://www.genome.jp/kegg/pathway.html]. The expression levels of miR-29-family target genes were verified using public database of Gene Expression Omnibus (GEO) in HNSCC clinical specimens. RESULTS: Expression levels of miR-29 family were significantly reduced in HNSCC clinical specimens compared to adjacent non-cancerous tissues (P<0.05). Restoration of each miR-29 family significantly inhibited cancer cell proliferation, migration, and invasion in the HNSCC cell lines. Our expression and in silico analysis showed that miR-29 family appeared to be an important modulator of tumor cell processes through suppression of many targets, particularly those involved in “focal adhesion” and “ECM (extra-cellular matrix)-receptor interaction” signaling pathways (P<0.05). Among two pathways, seven genes were putative targets regulated by miR-29 family (CAV2, CDC42, ITGA6, LAMC1, COL4A1, LAMC2, and COL6A1). Gene expression data showed that three genes (ITGA6, COL4A1 and LAMC2), were significantly up-regulated in clinical HNSCC tumor specimens compared with normal epithelium. CONCLUSIONS: miR-29 family functioned as pivotal suppressor of cell migration and invasion in HNSCC through targeting “focal adhesion” and “ECM” signaling pathways. Elucidation of tumor suppressive miR-29 family-mediated cancer pathways and putative targets might be provided the novel molecular mechanisms to understand local tumor recurrence or distant metastasis of HNSCC. Citation Format: Nijiro Nohata, Toyoyuki Hanazawa, Takashi Kinoshita, Naoko Kikkawa, Noriko Yamamoto, Hirofumi Yoshino, Toshihiko Itesako, Hideki Enokida, Masayuki Nakagawa, Yoshitaka Okamoto, Naohiko Seki. microRNA-29 family as tumor suppressive microRNAs in head and neck squamous cell carcinoma: microRNA-29a/b/c inhibits cell migration and invasion targeting focal adhesion and ECM pathways. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4182. doi:10.1158/1538-7445.AM2013-4182

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.

A Single Institution, Retrospective Study of Superselective Intra-arterial Cisplatin and Concomitant Radiation for Maxillary Sinus Squamous Cell Carcinomas

A Single Institution, Retrospective Study of Superselective Intra-arterial Cisplatin and Concomitant Radiation for Maxillary Sinus Squamous Cell Carcinomas

Neoadjuvant Chemoradiation in Squamous Cell Carcinoma of the Maxillary Sinus: A 26-Year Experience

Background. The aim of our study was to evaluate the effects of neoadjuvant platinum-based radiochemotherapy (RCT) in patients with maxillary sinus squamous cell carcinoma and to compare the results with other multimodality treatment concepts for advanced-stage maxillary sinus carcinoma in the literature. Methods. In total, 53 patients with squamous cell carcinoma of the maxillary sinus were reviewed retrospectively. All patients received a neoadjuvant RCT containing either cisplatin or carboplatin followed by radical surgery. Overall survival and locoregional control were plotted by Kaplan-Meier analysis. Prognostic factors were identified through univariate and multivariate analysis. Results. Five-year overall survival for all patients was 35%. Eleven patients achieved a complete response after radiochemotherapy. The complete response rate was significantly higher for patients treated with cisplatin (P = 0.028); however the 5-year overall survival rates did not differ significantly (P = 0.673) for patients treated with cisplatin (37%) and carboplatin (32%). Orbital invasion (P = 0.005) and complete response to radiochemotherapy (P = 0.021) had a significant impact on overall survival in univariate analysis. Conclusions. Neoadjuvant radiochemotherapy followed by radical surgery is an effective treatment for patients with advanced maxillary sinus squamous cell carcinoma. In terms of treatment response cisplatin seems to be more effective than carboplatin.

MicroRNAs function as tumor suppressors or oncogenes: Aberrant expression of microRNAs in head and neck squamous cell carcinoma

MicroRNAs (miRNAs) are endogenous short non-coding RNA molecules that regulate gene expression by repressing translation or cleaving RNA transcripts in a sequence-specific manner. Bioinformatic analyses predict that miRNAs regulate more than 30% of protein coding genes. To date, 1921 human mature miRNAs have been registered in miRBase release 18.0 (http://microrna.sanger.ac.uk/). A growing body of evidence suggests that miRNAs are aberrantly expressed in many human carcinomas and that they play key roles in the initiation, development and metastasis of human cancers, including head and neck squamous cell carcinoma (HNSCC). In this review, eight genome-wide miRNA expression profiles were used to selected aberrantly expressed miRNAs (up-regulated and down-regulated miRNAs) in HNSCC clinical specimens including our miRNA profiles of hypopharyngeal and maxillary sinus squamous cell carcinoma. We discuss recent findings on the aberrant expression of miRNAs and their contribution to human HNSCC oncogenesis.

First report of elective selective neck dissection in the management of squamous cell carcinoma of the maxillary sinus

Controversy remains about management of the neck in squamous cell carcinoma (SCC) of the maxillary sinus and we know of no reports of the use of elective selective neck dissection for management in this site. We retrospectively reviewed 18 consecutive patients with SCC of the maxillary sinus who were managed by primary operation with curative intent. A total of 13 patients had an elective selective neck dissection, which was invaded in one case 8%. Four patients had regional metastases, two with positive nodal disease confirmed after elective selective neck dissection, and two who developed regional recurrence (both after elective selective neck dissections which were negative (pN0)). A review of other published articles in the English language showed no cases of elective selective neck dissections reported. The mean regional recurrence rate was 12% (range 0–26%) and total mean regional metastases rate 21% (range 5–36%). Elective selective neck dissection did not contribute to an improved rate of neck control with regional recurrence of 11% (2/18) compared with 12% in the review. There is no evidence in this report to indicate that elective selective neck dissections for maxillary sinus SCC will result in better disease control. Future research may indicate fewer radiotherapy fields for necks with pathologically clear nodes after elective selective neck dissection.

Abstract 4143: microRNA-874 as a tumor suppressor in maxillary sinus squamous cell carcinoma based on microRNA expression signature

Abstract (BACKGROUND) Maxillary sinus squamous cell carcinoma (MSSCC) comprises 2-3% of all cancers of head and neck tumor and the annual incidence rate is 0.5-1.0 per 100,000 populations. After introduction of multimodality treatment comprising radiation therapy along with concomitant intra-arterial chemotherapy, rates of local control was improved. However the prognosis of advanced MSSCC is still worse. The 5-years survival rate of T4 tumors is 50% around. Local recurrence is the most common cause of treatment failure and death. Greater understanding of the molecular oncogenic network in MSSCC could help improve diagnosis, therapy, and prevention of the disease. No studies have been carried out for the purpose of identifying specific microRNA (miRNA) alterations in MSSCC. In this study, we focused on the functional siginificance of the most downregulated miRNA in MSSCC on the basis of miRNA expression signature. (METHODS) We used PCR-based methods to investigate the downregulated miRNAs in clinical specimens of MSSCC. Genome-wide gene expression analysis was performed to identify the molecular networks of microRNA-874 (miR-874) by microarray technique. Cell proliferation and invasion assays were performed to investigate the functional significance of miR-874 and its target genes in MSSCC cell lines. (RESULTS) Our miRNA signature identified that 23 miRNAs were significantly reduced in cancer cells. We focused on miR-874 as the most downregulated novel miRNA in our analysis. Ectopic miR-874 overexpression showed potential tumour suppressive functions such as inhibition of cancer cell proliferation and invasion. A molecular target search of miR-874 revealed that protein phosphatase 1, catalytic subunit, alpha isozyme (PPP1CA), proteasomal ATPase-associated factor 1 (PAAF1) and trans-golgi network protein 2 (TGOLN2) were regulated by miR-874. Overexpression of these genes was observed in MSSCC clinical specimens and each gene expression was inversely correlated with miR-874 expression. Moreover, silencing of the PPP1CA gene significantly inhibited cancer cell proliferation and invasion. (CONCLUSION) The downregulation of miR-874 was a frequent event in MSSCC, which suggests that miR-874 functions as a tumour suppressive miRNA, directly regulating PPP1CA that has a potential role of an oncogene. The identification of novel miR-874-regulated cancer network could provide new insights into potential molecular mechanisms of MSSCC oncogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4143. doi:1538-7445.AM2012-4143

Abstract 137: Molecular networks regulated by tumor suppressive microRNA-375 in head and neck squamous cell carcinoma

Abstract BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. In spite of considerable advances in multimodality therapy including surgery, radiotherapy and chemotherapy, the overall five-year survival rate for patients with HNSCC is around 40%. Understanding of the molecular oncogenic pathway underlying HNSCC could significantly improve diagnosis, therapy, and disease prevention. Our microRNA (miRNA) expression signatures of hypopharyngeal squamous cell carcinoma (SCC), maxillary sinus SCC and esophageal SCC revealed that the expression of microRNA-375 (miR-375) was significantly reduced in cancer tissues. In this study, we investigated the functional significance of miR-375 and explored novel molecular networks regulated by miR-375 in HNSCC. METHODS: Cell proliferation assay was performed to investigate the functional significance of miR-375 and its target genes in HNSCC cell lines. Genome-wide gene expression analysis was performed to identify the molecular networks of miR-375 by microarray technique. The expression levels of miR-375 target genes were verified using quantitative real-time RT-PCR in HNSCC clinical specimens. A luciferase reporter assay was used to identify the actual binding site between miR-375 and its candidate target genes. RESULTS: Restoration of miR-375 significantly inhibited cancer cell proliferation in HNSCC cells. Genome-wide molecular targets search and TargetScan database indicated that homocysteine-inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member 1 (HERPUD1), lactate dehydrogenase B (LDHB), PC4 and SFRS1 interacting protein 1 (PSIP1), metadherin (MTDH) and solute-carrier family 7, member 11 (SLC7A11) were the candidate genes of miR-375 target. Among them, the expression levels of LDHB and MTDH were significantly up-regulated in clinical HNSCC tumor specimens compared with adjacent normal epithelium. Luciferase reporter assay showed that LDHB and MTDH were directly regulated by miR-375. Silencing of these genes studies demonstrated significant inhibition of cell proliferation in HNSCC cells. CONCLUSIONS: miR-375 functions as a tumor suppressor in HNSCC. LDHB and MTDH are directly regulated by miR-375. These genes may function as oncogenes and contributed to cell proliferation in HNSCC. Tumor suppressive miR-375 and its target oncogenes may provide new insights into the molecular networks of HNSCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 137. doi:1538-7445.AM2012-137

Maxillary Sinus Squamous Cell Carcinoma With Concurrent Prolonged Foreign Body Impaction

Several elements in the maxillary sinus are reported to be carcinogenic. Also, foreign body reaction can cause cancer in any part of the body. We report a case of squamous cell carcinoma at the site in the maxillary sinus where a bullet splinter, analyzed as iron afterward, was inserted during the Korean War, approximately 60 years earlier.

Radiotherapy With or Without Surgery for Maxillary Sinus Squamous Cell Carcinoma

Maxillary sinus squamous cell carcinoma is commonly diagnosed at an advanced stage and treated using radiotherapy, with or without surgical resection. Fifty-four patients with maxillary sinus squamous cell carcinoma were treated from 1969 to 2006, using radiotherapy, with or without surgical resection. Fifty-two (96%) patients had American Joint Committee on Cancer stages III to IV disease, and 45 (83%) patients had N0 neck disease. Five-year local control (LC) rates by T-stage were 63% for T2/T3; and 43% for T4. Five-year LC rates for patients treated with radiotherapy preoperatively, postoperatively, and definitively were 61%, 65%, and 37%, respectively. Initially, overall 5-year LC, neck control, and local-regional control were 49%, 82%, and 45%, respectively. The ultimate 5-year LC, neck control, and local regional control after salvage of failures were 51%, 87%, and 50%, respectively. The overall 5-year cause-specific survival was 41%. Thirty-three percent of patients had a severe complication. Radiotherapy, with or without surgical resection, remains an effective tool in treating patients with this disease. LC, cause-specific survival, and complication rates need significant improvement. Treatment details and recommendations are discussed herein.

Tumor suppressive microRNA-375 regulates lactate dehydrogenase B in maxillary sinus squamous cell carcinoma

The expression of microRNA-375 (miR-375) is significantly reduced in cancer tissues of maxillary sinus squamous cell carcinoma (MSSCC). The aim of this study was to investigate the functional significance of miR-375 and a possible regulatory role in the MSSCC networks. Restoration of miR-375 significantly inhibited cancer cell proliferation and invasion in IMC-3 cells, suggesting that miR-375 functions as a tumor suppressor in MSSCC. Genome-wide gene expression data and luciferase reporter assays indicated that lactate dehydro-genaseB (LDHB) was directly regulated by miR-375. Cancer cell proliferation and invasion were significantly inhibited by transfection of si-LDHB into IMC-3 cells, suggesting that LDHB may play a role in MSSCC oncogenic function. In clinical MSSCC specimens, LDHB mRNA levels were up-regulated in cancer tissues, which were inversely correlated with the expression of miR-375. In addition, Kaplan-Meier curves and log-rank tests revealed that the high mRNA expression levels of LDHB had a significant adverse effect on survival rate. The identification of a cancer network regulated by the miR-375 tumor suppressor could provide new insights into the molecular mechanisms of MSSCC oncogenesis.

Tumour suppressive microRNA-874 regulates novel cancer networks in maxillary sinus squamous cell carcinoma.

Background:On the basis of the microRNA (miRNA) expression signature of maxillary sinus squamous cell carcinoma (MSSCC), we found that miR-874 was significantly reduced in cancer cells. We focused on the functional significance of miR-874 in cancer cells and identification of miR-874-regulated novel cancer networks in MSSCC.Methods:We used PCR-based methods to investigate the downregulated miRNAs in clinical specimens of MSSCC. Our signature analyses identified 23 miRNAs that were significantly reduced in cancer cells, such as miR-874, miR-133a, miR-375, miR-204, and miR-1. We focused on miR-874 as the most downregulated novel miRNA in our analysis.Results:We found potential tumour suppressive functions such as inhibition of cancer cell proliferation and invasion. A molecular target search of miR-874 revealed that PPP1CA was directly regulated by miR-874. Overexpression of PPP1CA was observed in MSSCC clinical specimens. Silencing of the PPP1CA gene significantly inhibited cancer cell proliferation and invasion.Conclusion:The downregulation of miR-874 was a frequent event in MSSCC, which suggests that miR-874 functions as a tumour suppressive miRNA, directly regulating PPP1CA that has a potential role of an oncogene. The identification of novel miR-874-regulated cancer pathways could provide new insights into potential molecular mechanisms of MSSCC oncogenesis.