The Sydney Head and Neck Cancer Institute

Sydney, Australia

The Sydney Head and Neck Cancer Institute

Sydney, Australia
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PubMed | University of Sydney, Royal Prince Alfred Hospital, University of New South Wales and The Sydney Head and Neck Cancer Institute
Type: Journal Article | Journal: Oral surgery, oral medicine, oral pathology and oral radiology | Year: 2016

Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy, with a proportion harboring MAML2 rearrangement. This study evaluates the diagnostic and prognostic utility of MAML2 rearrangement in MEC.Salivary gland malignancies at a single institution (1989-2014) were reviewed to identify MECs. Histopathologic evaluation, immunohistochemistry, and fluorescent in situ hybridization (FISH) were performed.Forty-one cases of MEC were identified, with mean age of 47 years and mean tumor size of 21 mm. Seven locoregional recurrences and five MEC-related deaths were seen over a 22-year follow-up period. Thirty-eight cases were suitable for FISH, and 31 (82%) cases were positive for MAML2 rearrangement, including the oncocytic and clear cell variants of MEC. FISH was negative in the morphologic mimics of MEC. MAML2 rearrangement was significantly associated with longer survival.MAML2 rearrangement is common and specific for MEC, which makes it a useful diagnostic tool. MAML2 rearrangement also predicts a favorable prognosis.


PubMed | University of Sydney, Royal Prince Alfred Hospital, University of New South Wales, The Sydney Head and Neck Cancer Institute and Westmead Hospital
Type: | Journal: Head & neck | Year: 2016

Accurate diagnosis of salivary duct carcinoma requires a high index of suspicion and clinicopathologic correlation. Hallmark genetic changes that may provide novel therapeutic options are being explored.One hundred ninety salivary gland malignancies at Royal Prince Alfred Hospital (from 1989-2014) were reviewed. Human epidermal growth factor receptor 2 (HER2) and androgen receptor status were determined along with multigene profiling.Twenty-three salivary duct carcinomas were identified, predominantly in men in their fifth to ninth decades of life. Facial nerve palsy (12%) and cervical lymph node metastases (82%) were present, and 96% received postoperative adjuvant therapy. Histologically, the tumors resembled high-grade invasive and in situ ductal carcinoma of the breast. Micropapillary, papillary, sarcomatoid, oncocytic, and mucinous variants were seen. The tumors showed androgen receptor (70%), HER2 amplification (30%), and HRAS, AKT1, PIK3CA, and NRAS mutations (22%; cumulative). The 5-year disease-free survival was 36%.Salivary duct carcinoma demonstrates a wide histopathologic spectrum. Treatment strategies need to take androgen receptor, HER2 amplification, and PIK3CA mutation into account. 2015 Wiley Periodicals, Inc. Head Neck 38: E1838-E1847, 2016.


Zhang X.,The Sydney Head and Neck Cancer Institute | Zhang X.,University of Sydney | Gee H.,Weatherall Institute of Molecular Medicine | Gee H.,University of Sydney | And 15 more authors.
BMC Cancer | Year: 2016

Background: The rates of oropharyngeal cancers such as tonsil cancers are increasing. The tumour suppressor protein Programmed Cell Death Protein 4 (PDCD4) has been implicated in the development of various human cancers and small RNAs such as microRNAs (miRNAs) can regulate its expression. However the exact regulation of PDCD4 by multiple miRNAs in oropharyngeal squamous cell carcinoma (SCC) is not well understood. Results: Using two independent oropharyngeal SCC cohorts with a focus on the tonsillar region, we identified a miRNA profile differentiating SCC tissue from normal. Both miR-21 and miR-499 were highly expressed in tonsil SCC tissues displaying a loss of PDCD4. Interestingly, expression of the miRNA machinery, Dicer1, Drosha, DDX5 (Dead Box Helicase 5) and DGCR8 (DiGeorge Syndrome Critical Region Gene 8) were all elevated by greater than 2 fold in the tonsil SCC tissue. The 3'UTR of PDCD4 contains three binding-sites for miR-499 and one for miR-21. Using a wild-type and truncated 3'UTR of PDCD4, we demonstrated that the initial suppression of PDCD4 was mediated by miR-21 whilst sustained suppression was mediated by miR-499. Moreover the single miR-21 site was able to elicit the same magnitude of suppression as the three miR-499 sites. Conclusion: This study describes the regulation of PDCD4 specifically in tonsil SCC by miR-499 and miR-21 and has documented the loss of PDCD4 in tonsil SCCs. These findings highlight the complex interplay between miRNAs and tumour suppressor gene regulation and suggest that PDCD4 loss may be an important step in tonsillar carcinogenesis. © 2016 Zhang et al.


PubMed | Royal Brisbane Hospital, University of New South Wales, Toowoomba Ipswich Hospitals and The Sydney Head and Neck Cancer Institute
Type: | Journal: Head & neck | Year: 2016

Significant oral function is often lost after surgical therapy for head and neck cancer. The use of osseointegrated implants for reconstruction in patients with head and neck surgery has shown to significantly improve the quality of life for these patients. Variable success rates range from 99% to 70%.A retrospective audit of patient records was performed looking at cumulative survival of implants. Inclusion criteria were patients who were treated at 1 of 2 designated Australian Head and Neck Units and received oral osseointegrated implants.Fifty-nine patients were included for analysis. One hundred ninety-nine implants were placed into vascularized bone grafts (VBGs). There were 11 implant failures with an overall success rate of 94.5%. There was 1 significant adverse outcome with a pathological fracture of a flap after implant placement. Implant success in scapula and iliac crest flaps was comparable to fibula flaps.Implants placed into VBGs have a reasonable success rate in well-selected patients. 2016 Wiley Periodicals, Inc. Head Neck, 2016.


PubMed | The Sydney Head and Neck Cancer Institute, Curtin University Australia, Centenary Institute, Weatherall Institute of Molecular Medicine and 2 more.
Type: | Journal: BMC cancer | Year: 2016

The rates of oropharyngeal cancers such as tonsil cancers are increasing. The tumour suppressor protein Programmed Cell Death Protein 4 (PDCD4) has been implicated in the development of various human cancers and small RNAs such as microRNAs (miRNAs) can regulate its expression. However the exact regulation of PDCD4 by multiple miRNAs in oropharyngeal squamous cell carcinoma (SCC) is not well understood.Using two independent oropharyngeal SCC cohorts with a focus on the tonsillar region, we identified a miRNA profile differentiating SCC tissue from normal. Both miR-21 and miR-499 were highly expressed in tonsil SCC tissues displaying a loss of PDCD4. Interestingly, expression of the miRNA machinery, Dicer1, Drosha, DDX5 (Dead Box Helicase 5) and DGCR8 (DiGeorge Syndrome Critical Region Gene 8) were all elevated by greater than 2 fold in the tonsil SCC tissue. The 3UTR of PDCD4 contains three binding-sites for miR-499 and one for miR-21. Using a wild-type and truncated 3UTR of PDCD4, we demonstrated that the initial suppression of PDCD4 was mediated by miR-21 whilst sustained suppression was mediated by miR-499. Moreover the single miR-21 site was able to elicit the same magnitude of suppression as the three miR-499 sites.This study describes the regulation of PDCD4 specifically in tonsil SCC by miR-499 and miR-21 and has documented the loss of PDCD4 in tonsil SCCs. These findings highlight the complex interplay between miRNAs and tumour suppressor gene regulation and suggest that PDCD4 loss may be an important step in tonsillar carcinogenesis.

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