Virtual Library
Start Your Search
Ashleigh Jean Hocking
Author of
-
+
P1.09 - Mesothelioma (ID 695)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Mesothelioma
- Presentations: 2
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
-
+
P1.09-003 - Malignant Mesothelioma Versus Synovial Sarcoma: An Analysis of 19 Cases with Molecular Diagnosis (ID 9390)
09:30 - 09:30 | Author(s): Ashleigh Jean Hocking
- Abstract
Background:
Intrathoracic synovial sarcomas (SSas) are well documented in the literature and characterized by a distinctive t(X;18) translocation. The histologic appearances of a monophasic or biphasic SSa can lead to confusion with biphasic or sarcomatoid mesothelioma (MM). The distinction of pleural SSa from pleural MM is important, because SSas may be responsive to ifosfamide-based chemotherapy and have no proven causal relationship to prior asbestos exposure. Demonstration of the t(X;18) by cytogenetics, fluorescence in situ hybridization (FISH) or reverse-transcriptase polymerase chain reaction is the gold standard for diagnosis, but availability of molecular diagnosis can be limited and testing is time consuming. Recently, it has been suggested that immunohistochemistry (IHC) for transducin-like enhancer of split 1 (TLE) is reliable for diagnosis of SSa and may replace molecular diagnosis.
Method:
We reviewed 19 pleura-based malignancies that had either been referred for a potential diagnosis of SSa, or where SSa was a differential diagnosis considered by the authors, based on morphology. Only cases with molecular diagnostics and clinical follow-up and blocks or unstained slides for further IHC studies are included.
Result:
Fourteen (14/19) cases were diagnosed as MM with morphology indistinguishable from SSa, based on lack of the t(X;18) by FISH and/or PCR, whereas 5 cases were diagnosed as SSa based on molecular diagnostics in conjunction with morphology. The mean age at diagnosis was 40.6 and 70.35 years for SSa and MM respectively. In the MM group, 21% of the patients were female, compared to 80% in the SSa group. Median survival after diagnosis was 9 months for MM, whereas all of the SSa patients were alive after follow-ups ranging from 3 months to 21 years. On average, MMs were larger tumours (average size of 97 mm, ranging from 20 to 220 mm), compared to 37 mm (range 20-50 mm) in SSa. Pleural plaques were present in 9 of the MM patients, with no information on plaques for 4 patients, and with 1 patient not having plaques, whereas only one of the SSa patients was confirmed as having pleural plaques. Of note, 7 of the MMs showed positive labelling for TLE1, with 7 MM not showing labelling, whereas all 5 SSas showed positive labelling.
Conclusion:
This indicates that positive labeling for TLE1 in isolation is insufficient for discrimination between MM vs SSa in pleura-based lesions with SSa-like morphology, and that molecular studies remain the gold standard for diagnosis.
-
+
P1.09-012 - A Pre-Clinical Investigation of Intrapleural Curcumin Treatments as an Adjunct Therapy for Malignant Pleural Mesothelioma (ID 9312)
09:30 - 09:30 | Presenting Author(s): Ashleigh Jean Hocking
- Abstract
Background:
Malignant pleural mesothelioma (MPM) is an aggressive malignancy originating in pleural mesothelial cells with median survivals of approximately 12 months following diagnosis. Recently, anti-angiogenic therapies have been trialled with only a modest effect. This may be, in part, due to alternative mechanisms of tumour vascularisation such as vasculogenic mimicry (VM), the ability of tumour cells to form fluid carrying vascular channels. Curcumin, a polyphenol extracted from the spice turmeric, has numerous anti-cancer and anti-inflammatory properties. Our aims were to investigate the effect of curcumin on vasculogenic mimicry and to determine if curcumin acts by disrupting microRNA profiles of mesothelioma cells. In preparation for future clinical trials, we evaluated the safety of curcumin treatments in vivo, when applied to the pleural cavity.
Method:
Mesothelioma cell lines NCl-H226 and NCI-H28, as well as patient-derived primary mesothelioma cells isolated from pleural effusions, were used for in vitro experiments. Matrigel tube formation assays were performed to assess if curcumin could inhibit VM in vitro. Small RNAseq was performed to determine if 6 h curcumin (20 mM) treatments had an effect on microRNA expression. Curcumin (80 mg/kg) was injected into the pleural cavity of Fischer 344 rats (n=6) and blood was taken at 1.5 h, 24 h, 48 h, 7 days, 14 days and 21 days. Rats were euthanized at 48 h, 1 week and 3 weeks (n=2). Parietal pleura, lung, kidney, liver brain and heart tissues were obtained and examined for signs of gross tissue damage and histopathological changes such as inflammation, and necrosis. Curcumin plasma and concentrations were measured using UPLC-MS to determine systemic distribution of curcumin following intrapleural treatments.
Result:
Non-cytotoxic curcumin treatments (20-10 mM) significantly inhibited the ability of mesothelioma cells to perform vasculogenic mimicry in vitro in a dose dependent manner. The microRNA expression profiles differed greatly between each mesothelioma sub-type. Minimal curcumin-induced change was observed, however differential expression analysis revealed some potential microRNA targets. No adverse effects were observed following intrapleural curcumin administration. Encapsulated curcumin deposits were observed in the pleural cavity of rats at 1 and 3 weeks following curcumin administration. Histological analysis revealed focal reactive mesothelial hyperplasia and a histiocytic response towards curcumin. Lung, liver, heart, brain and kidney tissues all display normal histological appearances. Curcumin was detected in the plasma samples of rats receiving intrapleural curcumin with peak concentration observed at 1.5 h post curcumin treatment (387-100 µg/ml).
Conclusion:
Intrapleural curcumin treatments may be suitable as adjunct treatment for MPM.
