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K. Mikami
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P3.03 - Poster Session with Presenters Present (ID 473)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 2
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.03-016 - Association between the Stainability of the Neurofibromatosis Type 2 Gene-Related Protein Merlin and the Tumor Properties of Mesotheliomas (ID 5680)
14:30 - 14:30 | Author(s): K. Mikami
- Abstract
Background:
Mutations in the genes cyclin-dependent kinase inhibitor 2A (CDKN2A), BRCA-1 associated protein 1 (BAP1), and neurofibromatosis type 2 (NF2) are observed in malignant pleural mesothelioma (MPM). We observed biallelic BAP1 alterations in 61% of MPMs and found that mutations are particularly frequent in epithelioid-type malignant mesotheliomas (Cancer Sci, 103:868-74, 2012). In addition, Loss-of-function mutations in NF2 are relatively frequent (40%) in MPMs have indicated. Merlin is a tumor suppressor protein coded by NF2; both merlin and the ezrin/radixin/moesin proteins are associated with suppression of invasion and metastasis of tumor cells. In this study, we examined the association between stainability of merlin and the tumor properties of MPM.
Methods:
Following definitive histological diagnoses of 35 cases of MPM (epithelial: n=31, biphasic: n=2, desmoplastic: n=2), we conducted immunohistochemical staining for merlin in thin sections of paraffin-embedded tumor tissue. Stainability was assessed with H-scores. The clinical stage of MPM was defined at the time near the tumor tissue harvesting time; the association between the clinical stage and therapeutic outcomes was assessed based on the outcomes of first-line chemotherapy with cisplatin (CDDP) or carboplatin(CBDCA) plus pemetrexed (PEM). The anti-merlin antibody used was LS-B394 (LSBio, Seattle, Washington, USA).
Results:
1) Seven MPMs (20%) were negative or weakly positive for merlin (H-score 0-30); of these seven MPMs, one was desmoplastic, while six were epithelial. Six MPMs were strongly positive for merlin (H-score ≥250); all six of these MPMs were epithelial. 2) No difference in merlin stainability was observed between epithelial (n=31) and non-epithelial (n=4) MPMs. Similarly, on examination of the association between stainability and IMIG staging, no differences in stainability were observed between stages 1 to 4. 3) No differences in stainability were observed between the first-line chemotherapy partial response group and progressive disease group.
Conclusion:
Loss-of-function mutations in the tumor suppressor gene NF2 lead to enhanced expression of focal adhesion kinase; although these mutations are demonstrated in decreased normal expression of the tumor suppressor protein merlin, no trend was observed in the morphological differentiation patterns of MPM. In addition, although the ratio of cells with high aldehyde dehydrogenase enzymatic activity is increased by CDDP/PEM treatment, we observed no association between CDDP/PEM sensitivity and merlin stainability. The association between NF2/merlin and tumor properties must be studied in more cases.
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P3.03-032 - PET/CT for Patients with Very Early Clinical Stage of Malignant Pleural Mesothelioma: When Can PET/CT Detect Tumor Growth of T0/T1a Mesothelioma? (ID 5725)
14:30 - 14:30 | Author(s): K. Mikami
- Abstract
Background:
Positron Emission Tomography/Computed Tomography (PET/CT) is well recognized as an important modality to detect malignant neoplasm, which plays a crucial role in the assessment of patients with malignant pleural mesothelioma (MPM). T1a category of IMIG classification refers to an early tumor that involves the parietal pleura only. And, there are a certain number of patients with more earlier clinical stage than T1a, i.e., radiological and thoracoscopical T0 stage. Those patients with T0 stage have neither visible pleural tumor nor pathologic PET/CT findings, and they are sometimes misdiagnosed as nonspecific pleuritis after a complete investigation including thoracoscopical biopsies. Those patients will turn out to be malignant during follow-up period. The purpose of this study was to investigate when tumor growth came to be detectable with PET/CT in patients with very early clinical stage of MPM whose PET/CT had been negative.
Methods:
Seven histologically-proven MPM patients with T0/T1a clinical stage were followed up with PET/CT (Epithelioid/unknown;6/1). A surgical thoracoscopy(VATS) or medical thoracoscopy with narrow band and autofluorescence imaging in addition to white light had been performed to obtain adequate materials of pleura and to diagnose T1-stage macroscopically. No patients had received talc pleurodesis. The initial thoracic CT scans showed pleural effusion without thickening of pleura, and all of the initial PET/CT evaluation was negative. The radiological examinations, including PET/CT and contrast and/or plain CT for loco-regional disease were reviewed to see tumor growth that came to be able to detect with PET scan. Interpretation of positive PET scan for malignancy is SUV>2.5.
Results:
The median interval between the initial PET/CT and the follow-up PET scan to come to identify malignant nodules for the first time was 32 months (5 - 46 months). Two patients with epithelioid and unknown MPM showed a positive finding of PET scan at the site of pleural intervention (thoracoscopy/thoracentesis), of which interval were 5 and 8 months, respectively. PET-positive pleural nodules, 5.1 ～ 8.2 mm in diameter, were demonstrated in 4 patients. And, a diffuse pleural thickening with positive PET scan, 6.5 mm in thickness, was shown in 1 patient with epithelioid MPM.
Conclusion:
PET/CT is a valuable modality for detecting the progression of T0/T1a tumors > 5 mm in diameter. Interval between PET-negative T0/T1a tumor and PET-positive tumor growth is more than 2 years (median; 32 months), and tumor seeding at the site of previous pleural intervention is an early manifestation of MPM.
