- Email: [email protected]
81 The uniqueness of the United Kingdom Lung Cancer Screening trial (UKLS) – a population screening study
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Poster abstracts, 11th Annual British Thoracic Oncology Group Conference, 2013: Diagnosis & Staging
who had Stereotactic Body Radiation Therapy (SBRT) & 39 pts who had Surgery. 37 pts did not have surgery and only 9 pts had a single identifiable reason for not being considered for surgery. 7 pts were upstaged and 14 downstaged when comparing PET scan to pathology. Conclusion: Our audit shows the importance of accuracy in data collection and subsequent uploading and as a result our trust has moved to a live data entry system during our MDT. More accurate data collection will allow trusts to be judged more accurately on their performance and also provide more accurate trends in key areas such as resection rates, histology and stage at presentation. Our audit also indicates that SBRT is likely to become a more common modality of treatment. 79 Pulmonary neuroendocrine tumours: diagnostic and prognostic factors L. Dunphy1 *, N. Murukesh2 , D.R. Ferry2 . 1 University of Birmingham, UK, 2 New Cross Hospital, Royal Wolverhampton Hospitals NHS Trust, UK Introduction: Neuroendocrine tumours comprise a heterogenous group of tumours that develop from neuroendocrine cells, which are capable of producing polypeptides and biogenic amines. Neuroendocrine tumours of the lung are clinically and pathologically diverse. They are not a well defined group in the WHO classification being classified into four histopathological types and three malignancy grades. The commonest lung neuroendocrine tumour is the small cell carcinoma, frequently presenting with bulky central disease, mediastinal invasion and distant metastases. The large cell neuroendocrine (LCNE) tumour is an aggressive variant of large cell carcinoma of the lung, which has poor survival in most series, resembling that of SCLC. LCNE tumours differ from typical and atypical carcinoids in terms of its greater quantity of mitosis and abundant necrosis, while it differs from SCLC in terms of its cytologic characteristics. Its tumour cells frequently express enzymes such as neurospecific enolase and specific neuroendocrine markers (chromogranin) and neural cell adhesion molecules (synaptophysin). We report our retrospective assessment of 19 cases. Methods: A retrospective review of 100 patients diagnosed with a primary lung tumour over a six month period. Data was retrieved from the Somerset Cancer Registry. Histo-pathological analysis of all specimens confirmed the diagnosis of SCLC in 10 patients and a large cell neuroendocrine tumour in 9 cases. The majority of patients were diagnosed with an adenocarcinoma (45), squamous cell (26) and NSCL NOS (10). Data was analysed to test for correlation with age, gender, ethnicity and smoking status. Results: See the table. Small cell lung cancer
Large cell neuroendocrine tumour
N Mean age Performance status Stage I IV Active treatment
10 66 years 2
9 63 years 2
IV (10)
II (2), III (3), IV (4)
Surgery Chemotherapy Radiation therapy Survival in months
0 8 2 2
4 5 0 1
Conclusion: The results from this study highlight distinctive clinical features and prognostic indicators in large cell neuroendocrine tumours involving the lung. Further study of large cell neuroen-
docrine lung tumours may identify risk factors associated with poor prognosis which could enable future clinical trial design. 80 Can stair assessment be standardised? A different and interesting approach to this simple test F. Jama *, I. Moore, T.J. Warke, M. Doherty, J. Maguire, A. Robinson, N. Magee. Belfast City Hospital, Belfast HSC Trust, Ireland, UK Introduction: Assessment of cardiopulmonary function is necessary for patients before consideration for radical treatment for lung cancer. Simple tests such as stair assessment has become pivotal and increasingly popular, saving costs and waiting times. It also allows functional assessment in centres with no access to cardiopulmonary exercise stress testing. Method: We compared stair assessment of approximately 30 patients with lung cancer in two institutions (A and B). Both institutions used a self-paced maximal stair climb. Using a portable pulse oximeter the duration, distance [m], oxygen saturations and heart rate were recorded. In institution A, a free iphone app called ‘Metronome’ was used to pace a further 34 patients. This was set at 60 steps/min. All patients in both institutions were accompanied by lung cancer specialist nurse who interacted with them and assessed their symptoms. They also gave valuable feedback on their overall performance. Results: Stair climbs at institution A was significantly faster and shorter than at institution B [p < 0.001]. Mean height at institution A was 12.8 m [range 5.1 27.2] and at institution B was 22.9 m [range 13.3 28]. Mean height at institution A after pacing with metronome was 16.6 m. This was significantly higher than the self paced climbs in the same institution [p = 0.008]. Conclusion: Maximal stair climbs can produce significantly different results depending on the speed of the ascent. We have shown that it is possible to pace these low technology tests using a phone application in order to standardise results. 81 The uniqueness of the United Kingdom Lung Cancer Screening trial (UKLS) a population screening study F. McRonald1 *, D.R. Baldwin2 , A. Devaraj3 , K. Brain4 , T. Eisen5 , J. Holeman6 , M. Ledson6 , N. Screaton7 , R.C. Rintoul7 , G. Yadegarfar1 , C. Hands1 , K. Lifford4 , D. Whynes4 , K.M. Kerr8 , R. Page6 , M. Parmar9 , D. Weller10 , P. Williamson1 , D. Hansell11 , S.W. Duffy12 , J.K. Field1 . 1 University of Liverpool, UK, 2 University of Nottingham, UK, 3 St. George’s Hospital, London, UK, 4 Cardiff University School of Medicine, UK, 5 University of Cambridge, UK, 6 Liverpool Heart & Chest Hospital, UK, 7 Papworth Hospital, Cambridge, UK, 8 Aberdeen Royal Infirmary, UK, 9 Medical Research Council, London, UK, 10 University of Edinburgh, UK, 11 Royal Brompton Hospital, London, UK, 12 Wolfson Institute, Barts & London University, UK Background: Lung Cancer causes 33,000 UK deaths per year, and early detection is currently the only foreseeable way to improve survival. Methods: UKLS is a pilot RCT, utilising CT screening of individuals at high lung cancer risk (>5% over 5 yrs). Results: UKLS is unique in a number of respects. It is populationbased, approaching people of 50 75 yrs through local PCT records. By contrast, other lung cancer screening studies use public advertising, thus allowing more potential for response bias. Using a validated lung cancer risk prediction model (Raji et al., 2012), UKLS identifies high risk individuals, thus targets resources to those most likely to benefit from screening. UKLS uses volumetric analysis of lung nodules identified on CT scan: this has only been used to any extent by one other trial (the Dutch-Belgian NELSON trial; van Klaveren et al., 2009). UKLS is also unique in having a formal Care Pathway plan, based on categorisation (size; volume) of lung nodules (Baldwin et al., 2011).
Poster abstracts, 11th Annual British Thoracic Oncology Group Conference, 2013: Mesothelioma Of 88,897 individuals approached in Liverpool and Cambridgeshire, 26.8% responded positively to the first questionnaire. People aged 50 55 yr were least likely to respond, and at lowest lung cancer risk: only five of 26,532 attended clinic. Response rate increased with socioeconomic status (SES), varying from 19.6% in the lowest Index of Multiple Deprivation (IMD) quintile to 34.2% in the highest quintile. However, as lung cancer risk decreased with SES, the socioeconomic distribution in high risk responders was very similar to that of the 88,897 approached. Conclusion: UKLS is a true population-based study. We have identified high risk individuals in relatively equal proportions across all IMD quintiles, but demonstrated that very few people aged 50 55 yr are at high risk. These observations may have implications for cost effectiveness; consideration needs to be given to inclusion criteria for any future UK screening trial.
Mesothelioma 82 Inhibition of RON (MST1R) induces apoptosis and decreases the cellular migration and proliferation capacity of mesothelioma cells A.M. Baird1,2 *, K.J. O’Byrne2,3 , D. Easty2 , A. Soltermann4 , D. Nonaka5 , D.A. Fennell6 , L. Mutti7 , H.I. Pass5 , I. Opitz4 , S.G. Gray2,3 . 1 Dept. of Clinical Medicine, Trinity College Dublin, Ireland, 2 Thoracic Oncology Research Group, Institute of Molecular Medicine, St. James’s Hospital, Dublin, Ireland, 3 HOPE Directorate, St. James’s Hospital, Dublin, Ireland, 4 Zurich University, Switzerland, 5 NYU School of Medicine, USA, 6 MRC Toxicology Unit, University of Leicester & Leicester University Hospitals, UK, 7 Dept. of Medicine, Vercelli Hospital, Italy Introduction: RON (MST1R) is a member of the MET family and has a putative role in several cancers. The only ligand recognised to bind MST1R is macrophage stimulating protein (MSP). The MSPRON signalling pathway has been implicated in a variety of cellular functions such as macrophage activity and wound healing. We have previously identified MST1R/RON as frequently activated in MPM, and high positivity for RON staining was an independent predictor of favourable prognosis. This study aimed to further examine the MSP-RON axis in MPM. Methods: A panel of mesothelioma cell lines were screened for the expression of MSP and MST1R at the mRNA and protein level. Proliferation, migration and apoptotic assays were performed using MSP and two MST1R/RON inhibitors (a) a pre-clinical monoclonal antibody (RON8, Imclone) and (b) a small molecule inhibitor (LCRF004). Additionally, a series of MPM TMAs were stained for both MSP and CD68 (macrophage) markers. Results: MSP and MST1R expression varied in our cell line panel at both the mRNA and protein level. Treatment with recombinant MSP reduced the proliferative capacity of the Met5A cells. However, MSP stimulation modified the expression of the SRC family of kinases. In terms of targeting MST1R/RON, LCRF-004 resulted in a significant decrease in proliferation and migration. Although treatment with RON8 had no effect on proliferation, it did affect the migration capacity of the MPM cells. MSP was identified as an independent prognosticator for survival in MPM. Conclusion: The RON receptor has a number of different isoforms, the most common of which are flRON (full length) and sf (short form). Our results indicate that although high levels of RON and MSP correlate with increased survival, our in vitro observations would indicate that this may be isoform dependant. Studies are ongoing to further elucidate the RON-MSP axis in MPM.
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83 HDAC expression levels may play a role in cisplatin resistant MPM A.M. Baird1,2 *, C.J. Jennings3 , L. Flynn2 , E. O’Donnell2 , M.P. Barr2,4 , E. Santoni-Rugiu5 , Y. Takiguchi6 , W. Thomas3 , Z.G. Zimling5 , K.J. O’Byrne2,4 , S.G. Gray2,4 . 1 Dept. of Clinical Medicine, Trinity College Dublin, Ireland, 2 Thoracic Oncology Research Group, Institute of Molecular Medicine, St. James’s Hospital, Dublin, Ireland, 3 Dept. of Molecular Medicine, Royal College of Surgeons in Ireland, Ireland, 4 Education and Research Centre, Beaumont Hospital, Dublin, Ireland, 4 HOPE Directorate, St. James’s Hospital, Dublin, Ireland, 5 Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark, 6 Dept. of Medical Oncology, Chiba University, Japan Introduction: Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer. The severity of this disease is underscored by the fact that no single treatment option has proven particularly effective. However, epigenetic modifiers, such as histone deacetylase inhibitors (HDACi) have emerged as a novel class of anti-cancer agent and are currently undergoing clinical trials in numerous solid cancers. We investigated the levels of HDACs in both MPM cell lines and patient samples. Methods: A panel of MPM cell lines (n = 16) were screened for the expression of HDAC11, Class I (HDAC1/2/3/8) and Class II (HDAC4/5/6/7/9/10) HDACs by RT-PCR and western blotting. The HDAC expression profile was also determined in an isogenic cisplatin sensitive and resistant MPM cell line model (P31). In addition, HDAC expression was examined in panel of twenty patient samples (benign, biphasic, sarcomatoid, epithelial). A cohort of MPM patient samples have been stained by immuno-histochemistry for HDAC5 expression and are currently being scored. Results: HDAC11, Class I and II HDACs were detected to varying degrees within our cell line panel. In the P31 cell line, HDAC protein expression was decreased (HDAC2/3/4/5/7) in the cisplatin resistant sub type compared with the parent with HDAC5 significantly reduced at both the protein and mRNA level (p < 0.05). The expression of HDAC1/2/3 were increased in the MPM patient samples (n = 15) compared with benign (n = 5) (HDAC2/3, p < 0.05). We hope to present the interim results for IHC scoring of HDAC5 expression at the meeting. Conclusion: Altered HDAC expression was observed in an isogenic parent and cisplatin resistant cell model, which may suggest that a reduction in HDAC expression is involved in cisplatin resistance. Conversely, an increase in the protein levels of HDAC1/2 and 3 were detected in MPM patient samples, which may be important in stratifying patients for epigenetic targeted therapies. 84 Tamoxifen induced signalling in the suppression of malignant pleural mesothelioma cell growth C.J. Jennings1 *, N. Zainal1 , I.M.M. Dahlan1 , E.W. Kay2 , B.J. Harvey1 , W. Thomas1 . 1 Departments of Molecular Medicine, Ireland, 2 Histopathology, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland Introduction: Malignant pleural mesothelioma (MPM) is a highly aggressive tumour for which female gender is a positive prognostic indicator. The enhanced post-diagnosis survival of female subjects has been attributed to hormonal factors influenced by expression of oestrogen receptor (ER)-b. The ER partial agonist/antagonist, tamoxifen was used in conjunction with cisplatin to treat a small cohort of MPM cases in a clinical study, and tamoxifen was found to have some benefit. Methods: ERa and ERb expression in MPM tumour samples was evaluated by immuno-histochemistry (IHC) and by Western blotting in MPM cell lines. Cell viability assays were carried out on MPP89 (epithelioid), REN (epithelioid), Msto-211H (biphasic) and H2052 (sarcomatoid) MPM cell lines treated with varying concentrations of
Poster abstracts, 11th Annual British Thoracic Oncology Group Conference, 2013: Diagnosis & Staging
who had Stereotactic Body Radiation Therapy (SBRT) & 39 pts who had Surgery. 37 pts did not have surgery and only 9 pts had a single identifiable reason for not being considered for surgery. 7 pts were upstaged and 14 downstaged when comparing PET scan to pathology. Conclusion: Our audit shows the importance of accuracy in data collection and subsequent uploading and as a result our trust has moved to a live data entry system during our MDT. More accurate data collection will allow trusts to be judged more accurately on their performance and also provide more accurate trends in key areas such as resection rates, histology and stage at presentation. Our audit also indicates that SBRT is likely to become a more common modality of treatment. 79 Pulmonary neuroendocrine tumours: diagnostic and prognostic factors L. Dunphy1 *, N. Murukesh2 , D.R. Ferry2 . 1 University of Birmingham, UK, 2 New Cross Hospital, Royal Wolverhampton Hospitals NHS Trust, UK Introduction: Neuroendocrine tumours comprise a heterogenous group of tumours that develop from neuroendocrine cells, which are capable of producing polypeptides and biogenic amines. Neuroendocrine tumours of the lung are clinically and pathologically diverse. They are not a well defined group in the WHO classification being classified into four histopathological types and three malignancy grades. The commonest lung neuroendocrine tumour is the small cell carcinoma, frequently presenting with bulky central disease, mediastinal invasion and distant metastases. The large cell neuroendocrine (LCNE) tumour is an aggressive variant of large cell carcinoma of the lung, which has poor survival in most series, resembling that of SCLC. LCNE tumours differ from typical and atypical carcinoids in terms of its greater quantity of mitosis and abundant necrosis, while it differs from SCLC in terms of its cytologic characteristics. Its tumour cells frequently express enzymes such as neurospecific enolase and specific neuroendocrine markers (chromogranin) and neural cell adhesion molecules (synaptophysin). We report our retrospective assessment of 19 cases. Methods: A retrospective review of 100 patients diagnosed with a primary lung tumour over a six month period. Data was retrieved from the Somerset Cancer Registry. Histo-pathological analysis of all specimens confirmed the diagnosis of SCLC in 10 patients and a large cell neuroendocrine tumour in 9 cases. The majority of patients were diagnosed with an adenocarcinoma (45), squamous cell (26) and NSCL NOS (10). Data was analysed to test for correlation with age, gender, ethnicity and smoking status. Results: See the table. Small cell lung cancer
Large cell neuroendocrine tumour
N Mean age Performance status Stage I IV Active treatment
10 66 years 2
9 63 years 2
IV (10)
II (2), III (3), IV (4)
Surgery Chemotherapy Radiation therapy Survival in months
0 8 2 2
4 5 0 1
Conclusion: The results from this study highlight distinctive clinical features and prognostic indicators in large cell neuroendocrine tumours involving the lung. Further study of large cell neuroen-
docrine lung tumours may identify risk factors associated with poor prognosis which could enable future clinical trial design. 80 Can stair assessment be standardised? A different and interesting approach to this simple test F. Jama *, I. Moore, T.J. Warke, M. Doherty, J. Maguire, A. Robinson, N. Magee. Belfast City Hospital, Belfast HSC Trust, Ireland, UK Introduction: Assessment of cardiopulmonary function is necessary for patients before consideration for radical treatment for lung cancer. Simple tests such as stair assessment has become pivotal and increasingly popular, saving costs and waiting times. It also allows functional assessment in centres with no access to cardiopulmonary exercise stress testing. Method: We compared stair assessment of approximately 30 patients with lung cancer in two institutions (A and B). Both institutions used a self-paced maximal stair climb. Using a portable pulse oximeter the duration, distance [m], oxygen saturations and heart rate were recorded. In institution A, a free iphone app called ‘Metronome’ was used to pace a further 34 patients. This was set at 60 steps/min. All patients in both institutions were accompanied by lung cancer specialist nurse who interacted with them and assessed their symptoms. They also gave valuable feedback on their overall performance. Results: Stair climbs at institution A was significantly faster and shorter than at institution B [p < 0.001]. Mean height at institution A was 12.8 m [range 5.1 27.2] and at institution B was 22.9 m [range 13.3 28]. Mean height at institution A after pacing with metronome was 16.6 m. This was significantly higher than the self paced climbs in the same institution [p = 0.008]. Conclusion: Maximal stair climbs can produce significantly different results depending on the speed of the ascent. We have shown that it is possible to pace these low technology tests using a phone application in order to standardise results. 81 The uniqueness of the United Kingdom Lung Cancer Screening trial (UKLS) a population screening study F. McRonald1 *, D.R. Baldwin2 , A. Devaraj3 , K. Brain4 , T. Eisen5 , J. Holeman6 , M. Ledson6 , N. Screaton7 , R.C. Rintoul7 , G. Yadegarfar1 , C. Hands1 , K. Lifford4 , D. Whynes4 , K.M. Kerr8 , R. Page6 , M. Parmar9 , D. Weller10 , P. Williamson1 , D. Hansell11 , S.W. Duffy12 , J.K. Field1 . 1 University of Liverpool, UK, 2 University of Nottingham, UK, 3 St. George’s Hospital, London, UK, 4 Cardiff University School of Medicine, UK, 5 University of Cambridge, UK, 6 Liverpool Heart & Chest Hospital, UK, 7 Papworth Hospital, Cambridge, UK, 8 Aberdeen Royal Infirmary, UK, 9 Medical Research Council, London, UK, 10 University of Edinburgh, UK, 11 Royal Brompton Hospital, London, UK, 12 Wolfson Institute, Barts & London University, UK Background: Lung Cancer causes 33,000 UK deaths per year, and early detection is currently the only foreseeable way to improve survival. Methods: UKLS is a pilot RCT, utilising CT screening of individuals at high lung cancer risk (>5% over 5 yrs). Results: UKLS is unique in a number of respects. It is populationbased, approaching people of 50 75 yrs through local PCT records. By contrast, other lung cancer screening studies use public advertising, thus allowing more potential for response bias. Using a validated lung cancer risk prediction model (Raji et al., 2012), UKLS identifies high risk individuals, thus targets resources to those most likely to benefit from screening. UKLS uses volumetric analysis of lung nodules identified on CT scan: this has only been used to any extent by one other trial (the Dutch-Belgian NELSON trial; van Klaveren et al., 2009). UKLS is also unique in having a formal Care Pathway plan, based on categorisation (size; volume) of lung nodules (Baldwin et al., 2011).
Poster abstracts, 11th Annual British Thoracic Oncology Group Conference, 2013: Mesothelioma Of 88,897 individuals approached in Liverpool and Cambridgeshire, 26.8% responded positively to the first questionnaire. People aged 50 55 yr were least likely to respond, and at lowest lung cancer risk: only five of 26,532 attended clinic. Response rate increased with socioeconomic status (SES), varying from 19.6% in the lowest Index of Multiple Deprivation (IMD) quintile to 34.2% in the highest quintile. However, as lung cancer risk decreased with SES, the socioeconomic distribution in high risk responders was very similar to that of the 88,897 approached. Conclusion: UKLS is a true population-based study. We have identified high risk individuals in relatively equal proportions across all IMD quintiles, but demonstrated that very few people aged 50 55 yr are at high risk. These observations may have implications for cost effectiveness; consideration needs to be given to inclusion criteria for any future UK screening trial.
Mesothelioma 82 Inhibition of RON (MST1R) induces apoptosis and decreases the cellular migration and proliferation capacity of mesothelioma cells A.M. Baird1,2 *, K.J. O’Byrne2,3 , D. Easty2 , A. Soltermann4 , D. Nonaka5 , D.A. Fennell6 , L. Mutti7 , H.I. Pass5 , I. Opitz4 , S.G. Gray2,3 . 1 Dept. of Clinical Medicine, Trinity College Dublin, Ireland, 2 Thoracic Oncology Research Group, Institute of Molecular Medicine, St. James’s Hospital, Dublin, Ireland, 3 HOPE Directorate, St. James’s Hospital, Dublin, Ireland, 4 Zurich University, Switzerland, 5 NYU School of Medicine, USA, 6 MRC Toxicology Unit, University of Leicester & Leicester University Hospitals, UK, 7 Dept. of Medicine, Vercelli Hospital, Italy Introduction: RON (MST1R) is a member of the MET family and has a putative role in several cancers. The only ligand recognised to bind MST1R is macrophage stimulating protein (MSP). The MSPRON signalling pathway has been implicated in a variety of cellular functions such as macrophage activity and wound healing. We have previously identified MST1R/RON as frequently activated in MPM, and high positivity for RON staining was an independent predictor of favourable prognosis. This study aimed to further examine the MSP-RON axis in MPM. Methods: A panel of mesothelioma cell lines were screened for the expression of MSP and MST1R at the mRNA and protein level. Proliferation, migration and apoptotic assays were performed using MSP and two MST1R/RON inhibitors (a) a pre-clinical monoclonal antibody (RON8, Imclone) and (b) a small molecule inhibitor (LCRF004). Additionally, a series of MPM TMAs were stained for both MSP and CD68 (macrophage) markers. Results: MSP and MST1R expression varied in our cell line panel at both the mRNA and protein level. Treatment with recombinant MSP reduced the proliferative capacity of the Met5A cells. However, MSP stimulation modified the expression of the SRC family of kinases. In terms of targeting MST1R/RON, LCRF-004 resulted in a significant decrease in proliferation and migration. Although treatment with RON8 had no effect on proliferation, it did affect the migration capacity of the MPM cells. MSP was identified as an independent prognosticator for survival in MPM. Conclusion: The RON receptor has a number of different isoforms, the most common of which are flRON (full length) and sf (short form). Our results indicate that although high levels of RON and MSP correlate with increased survival, our in vitro observations would indicate that this may be isoform dependant. Studies are ongoing to further elucidate the RON-MSP axis in MPM.
S29
83 HDAC expression levels may play a role in cisplatin resistant MPM A.M. Baird1,2 *, C.J. Jennings3 , L. Flynn2 , E. O’Donnell2 , M.P. Barr2,4 , E. Santoni-Rugiu5 , Y. Takiguchi6 , W. Thomas3 , Z.G. Zimling5 , K.J. O’Byrne2,4 , S.G. Gray2,4 . 1 Dept. of Clinical Medicine, Trinity College Dublin, Ireland, 2 Thoracic Oncology Research Group, Institute of Molecular Medicine, St. James’s Hospital, Dublin, Ireland, 3 Dept. of Molecular Medicine, Royal College of Surgeons in Ireland, Ireland, 4 Education and Research Centre, Beaumont Hospital, Dublin, Ireland, 4 HOPE Directorate, St. James’s Hospital, Dublin, Ireland, 5 Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark, 6 Dept. of Medical Oncology, Chiba University, Japan Introduction: Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer. The severity of this disease is underscored by the fact that no single treatment option has proven particularly effective. However, epigenetic modifiers, such as histone deacetylase inhibitors (HDACi) have emerged as a novel class of anti-cancer agent and are currently undergoing clinical trials in numerous solid cancers. We investigated the levels of HDACs in both MPM cell lines and patient samples. Methods: A panel of MPM cell lines (n = 16) were screened for the expression of HDAC11, Class I (HDAC1/2/3/8) and Class II (HDAC4/5/6/7/9/10) HDACs by RT-PCR and western blotting. The HDAC expression profile was also determined in an isogenic cisplatin sensitive and resistant MPM cell line model (P31). In addition, HDAC expression was examined in panel of twenty patient samples (benign, biphasic, sarcomatoid, epithelial). A cohort of MPM patient samples have been stained by immuno-histochemistry for HDAC5 expression and are currently being scored. Results: HDAC11, Class I and II HDACs were detected to varying degrees within our cell line panel. In the P31 cell line, HDAC protein expression was decreased (HDAC2/3/4/5/7) in the cisplatin resistant sub type compared with the parent with HDAC5 significantly reduced at both the protein and mRNA level (p < 0.05). The expression of HDAC1/2/3 were increased in the MPM patient samples (n = 15) compared with benign (n = 5) (HDAC2/3, p < 0.05). We hope to present the interim results for IHC scoring of HDAC5 expression at the meeting. Conclusion: Altered HDAC expression was observed in an isogenic parent and cisplatin resistant cell model, which may suggest that a reduction in HDAC expression is involved in cisplatin resistance. Conversely, an increase in the protein levels of HDAC1/2 and 3 were detected in MPM patient samples, which may be important in stratifying patients for epigenetic targeted therapies. 84 Tamoxifen induced signalling in the suppression of malignant pleural mesothelioma cell growth C.J. Jennings1 *, N. Zainal1 , I.M.M. Dahlan1 , E.W. Kay2 , B.J. Harvey1 , W. Thomas1 . 1 Departments of Molecular Medicine, Ireland, 2 Histopathology, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland Introduction: Malignant pleural mesothelioma (MPM) is a highly aggressive tumour for which female gender is a positive prognostic indicator. The enhanced post-diagnosis survival of female subjects has been attributed to hormonal factors influenced by expression of oestrogen receptor (ER)-b. The ER partial agonist/antagonist, tamoxifen was used in conjunction with cisplatin to treat a small cohort of MPM cases in a clinical study, and tamoxifen was found to have some benefit. Methods: ERa and ERb expression in MPM tumour samples was evaluated by immuno-histochemistry (IHC) and by Western blotting in MPM cell lines. Cell viability assays were carried out on MPP89 (epithelioid), REN (epithelioid), Msto-211H (biphasic) and H2052 (sarcomatoid) MPM cell lines treated with varying concentrations of