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ACTH-producing pituitary carcinoma
ABSTRACTS
Conclusion: On rare occasions, neuroendocrine carcinomas fail to express cytokeratins, causing diagnostic difficulty, especially in the metastatic setting. While almost all pulmonary, thyroid, and gastrointestinal neuroendocrine tumours are positive for cytokeratins, expression is less consistent in other sites. In particular, pancreatic, gynaecological and breast neuroendocrine carcinomas may lack cytokeratin expression in 1–10% of cases. In the appropriate morphologic context, awareness of this uncommon presentation is key to making the diagnosis so that appropriate chemotherapeutic agents may be utilised. 57. ACTH-PRODUCING PITUITARY CARCINOMA Mohammed Alswayyed, Angeline Shen, Michael Christie, TeWhiti Rogers, Michael Gonzales Anatomical Pathology and Endocrinology Departments, Royal Melbourne Hospital, Australia Pituitary carcinoma is rare, accounting for less than 0.2% of all pituitary neoplasms. Patients typically present with distant metastasis, having a history of a previous pituitary tumour diagnosed as pituitary adenoma. The latency between the initial presentation of a pituitary tumour and metastatic disease is variable. Persistent hormone secretion following pituitary adenoma resection is a marker of metastatic disease. Here we report a case of metastatic ACTH-producing pituitary carcinoma in a 51 year old gentleman, diagnosed three years prior with an ACTH-secreting pituitary adenoma. Following his initial pituitary surgery, his clinical and biochemical features of Cushing’s resolved. Two years later he re-presented with clinical and biochemical Cushing’s and was found to have a 30 mm parotid mass. Biopsy and resection revealed metastatic pituitary. The sequence of progression from adenoma to carcinoma is not well defined in pituitary tumours. Pituitary carcinoma demonstrates a poor prognosis with current standard treatment regimens. Nevertheless case reports show limited response to alkylating agent Temozolomide if the O6 methylguanine methyltransferase gene promoter (MGMT) is methylated. 58. SPECIFIC LOCALISATION OF LC3B IN AUTOPHAGOSOME: A CORRELATIVE LABELLING STUDY WITH NANOPARTICLE IN ORAL SQUAMOUS CELL CARCINOMA K. Lai1,2,3,4, M. Killingsworth2,3,4,5, N. Caixeiro3, J. L. C. Yong4, A. Hong6, C. S. Lee1,2,3,4 1 Sydney Medical School, The University of Sydney, 2Discipline of Pathology, School of Medicine, Western Sydney University, 3 Centre for Oncology Education and Research Translation (CONCERT), Ingham Institute for Applied Medical Research, 4 Department of Anatomical Pathology, Sydney South West Pathology Service (SSWPS) Liverpool Hospital, 5Faculty of Medicine, University of New South Wales, and 6Central Clinical School, University of Sydney, Sydney, Australia Background: Autophagy is a mechanism involved in the elimination of damaged cellular components and is capable of
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inducing programmed cell death. The process has recently gained much interest in cancer therapy due to its role in both pro- and anti-cancer activity. Microtubule-associated protein light chains 3 (LC3) is a specific marker for the autophagosome, an early stage of autophagy. The autophagosome is characterised by its double membrane limited spherical structure. However, such characteristics are also shown by swollen mitochondria, a common feature of tumour cells, thus complicating identification of autophagosomes and ultimately affecting result interpretation in cancer research. LC3B antibody is a common autophagosome marker and high LC3B expression associates with poor prognosis in various cancers including oral squamous cell carcinoma (SCC), however, the specificity of LC3B antibody to the autophagosome is yet to be investigated at the ultra structure level in human cancer tissue. Objectives: To investigate the localisation of LC3B antibody to the autophagosome using correlative immunolabelling with nanoparticle quantum dots (QDs). Methods: LC3B immunolabelling using streptavidin conjugated QDs was applied on the human oral SCC tissue and examined between fluorescence and transmission electron microscopy (TEM). Findings: LC3B labelling appeared as punctate staining under fluorescent microscopy. Correlative TEM examination revealed such staining to be specific labelling on the surface of the development stage of the autophagosome as well as within a matured autophagosome. Conclusions: This study confirmed the specific localisation of LC3B to the autophagosome. Furthermore, such a correlative labelling method would be useful to study autophagy at the ultrastructural level. 59. HIGH LC3C EXPRESSION CORRELATES WITH POOR SURVIVAL IN ORAL CAVITY SQUAMOUS CELL CARCINOMA PATIENTS K. Lai1,2,3,4, S. Matthews1,5, J. Wilmott1,6, M. Killingsworth2,3,4,7, N. Caixeiro3, J. Wykes8, A. Samakeh8, D. Forstner9, N. Niles8, A. Hong10, C. S. Lee1,2,3,4 1 Sydney Medical School, The University of Sydney, 2Discipline of Pathology, School of Medicine, Western Sydney University, 3 Centre for Oncology Education and Research Translation (CONCERT), Ingham Institute for Applied Medical Research, 4 Department of Anatomical Pathology, Sydney South West Pathology Service (SSWPS) Liverpool Hospital, 5Bosch Institute, The University of Sydney, 6Melanoma Institute Australia, 7Faculty of Medicine, University of New South Wales, 8 Department of Oncology, 9Department of Radiation Oncology, Liverpool Hospital, and 10Central Clinical School, University of Sydney, Sydney, Australia Background: Oropharyngeal (OSCC) and oral cavity squamous cell carcinoma (OCSCC) arise from the mucosa of the head and neck region and appeared to have different biology. Autophagy eliminates damaged cellular components and is also capable of inducing programmed cell death. The process has recently gained much interest in cancer therapy due to its role in both proand anti-cancer activity. Microtubule-associated protein light chains 3 (LC3) is a biomarker for autophagosome, an early stage
Conclusion: On rare occasions, neuroendocrine carcinomas fail to express cytokeratins, causing diagnostic difficulty, especially in the metastatic setting. While almost all pulmonary, thyroid, and gastrointestinal neuroendocrine tumours are positive for cytokeratins, expression is less consistent in other sites. In particular, pancreatic, gynaecological and breast neuroendocrine carcinomas may lack cytokeratin expression in 1–10% of cases. In the appropriate morphologic context, awareness of this uncommon presentation is key to making the diagnosis so that appropriate chemotherapeutic agents may be utilised. 57. ACTH-PRODUCING PITUITARY CARCINOMA Mohammed Alswayyed, Angeline Shen, Michael Christie, TeWhiti Rogers, Michael Gonzales Anatomical Pathology and Endocrinology Departments, Royal Melbourne Hospital, Australia Pituitary carcinoma is rare, accounting for less than 0.2% of all pituitary neoplasms. Patients typically present with distant metastasis, having a history of a previous pituitary tumour diagnosed as pituitary adenoma. The latency between the initial presentation of a pituitary tumour and metastatic disease is variable. Persistent hormone secretion following pituitary adenoma resection is a marker of metastatic disease. Here we report a case of metastatic ACTH-producing pituitary carcinoma in a 51 year old gentleman, diagnosed three years prior with an ACTH-secreting pituitary adenoma. Following his initial pituitary surgery, his clinical and biochemical features of Cushing’s resolved. Two years later he re-presented with clinical and biochemical Cushing’s and was found to have a 30 mm parotid mass. Biopsy and resection revealed metastatic pituitary. The sequence of progression from adenoma to carcinoma is not well defined in pituitary tumours. Pituitary carcinoma demonstrates a poor prognosis with current standard treatment regimens. Nevertheless case reports show limited response to alkylating agent Temozolomide if the O6 methylguanine methyltransferase gene promoter (MGMT) is methylated. 58. SPECIFIC LOCALISATION OF LC3B IN AUTOPHAGOSOME: A CORRELATIVE LABELLING STUDY WITH NANOPARTICLE IN ORAL SQUAMOUS CELL CARCINOMA K. Lai1,2,3,4, M. Killingsworth2,3,4,5, N. Caixeiro3, J. L. C. Yong4, A. Hong6, C. S. Lee1,2,3,4 1 Sydney Medical School, The University of Sydney, 2Discipline of Pathology, School of Medicine, Western Sydney University, 3 Centre for Oncology Education and Research Translation (CONCERT), Ingham Institute for Applied Medical Research, 4 Department of Anatomical Pathology, Sydney South West Pathology Service (SSWPS) Liverpool Hospital, 5Faculty of Medicine, University of New South Wales, and 6Central Clinical School, University of Sydney, Sydney, Australia Background: Autophagy is a mechanism involved in the elimination of damaged cellular components and is capable of
S141
inducing programmed cell death. The process has recently gained much interest in cancer therapy due to its role in both pro- and anti-cancer activity. Microtubule-associated protein light chains 3 (LC3) is a specific marker for the autophagosome, an early stage of autophagy. The autophagosome is characterised by its double membrane limited spherical structure. However, such characteristics are also shown by swollen mitochondria, a common feature of tumour cells, thus complicating identification of autophagosomes and ultimately affecting result interpretation in cancer research. LC3B antibody is a common autophagosome marker and high LC3B expression associates with poor prognosis in various cancers including oral squamous cell carcinoma (SCC), however, the specificity of LC3B antibody to the autophagosome is yet to be investigated at the ultra structure level in human cancer tissue. Objectives: To investigate the localisation of LC3B antibody to the autophagosome using correlative immunolabelling with nanoparticle quantum dots (QDs). Methods: LC3B immunolabelling using streptavidin conjugated QDs was applied on the human oral SCC tissue and examined between fluorescence and transmission electron microscopy (TEM). Findings: LC3B labelling appeared as punctate staining under fluorescent microscopy. Correlative TEM examination revealed such staining to be specific labelling on the surface of the development stage of the autophagosome as well as within a matured autophagosome. Conclusions: This study confirmed the specific localisation of LC3B to the autophagosome. Furthermore, such a correlative labelling method would be useful to study autophagy at the ultrastructural level. 59. HIGH LC3C EXPRESSION CORRELATES WITH POOR SURVIVAL IN ORAL CAVITY SQUAMOUS CELL CARCINOMA PATIENTS K. Lai1,2,3,4, S. Matthews1,5, J. Wilmott1,6, M. Killingsworth2,3,4,7, N. Caixeiro3, J. Wykes8, A. Samakeh8, D. Forstner9, N. Niles8, A. Hong10, C. S. Lee1,2,3,4 1 Sydney Medical School, The University of Sydney, 2Discipline of Pathology, School of Medicine, Western Sydney University, 3 Centre for Oncology Education and Research Translation (CONCERT), Ingham Institute for Applied Medical Research, 4 Department of Anatomical Pathology, Sydney South West Pathology Service (SSWPS) Liverpool Hospital, 5Bosch Institute, The University of Sydney, 6Melanoma Institute Australia, 7Faculty of Medicine, University of New South Wales, 8 Department of Oncology, 9Department of Radiation Oncology, Liverpool Hospital, and 10Central Clinical School, University of Sydney, Sydney, Australia Background: Oropharyngeal (OSCC) and oral cavity squamous cell carcinoma (OCSCC) arise from the mucosa of the head and neck region and appeared to have different biology. Autophagy eliminates damaged cellular components and is also capable of inducing programmed cell death. The process has recently gained much interest in cancer therapy due to its role in both proand anti-cancer activity. Microtubule-associated protein light chains 3 (LC3) is a biomarker for autophagosome, an early stage