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P. Carbognani
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P1.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 224)
- Event: WCLC 2015
- Type: Poster
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.08-017 - microRNAs Expression in Malignant Pleural Mesothelioma, Asbestosis and Benign Pulmonary Disease (ID 2663)
09:30 - 09:30 | Author(s): P. Carbognani
- Abstract
Background:
To evaluate the diagnostic potential of a panel of microRNAs in plasma samples of patients with malignant pleural mesothelioma (MPM).
Methods:
A group of patients with pathological diagnosis of MPM were randomly selected from a prospective mesothelioma database. Similarly, a group of patients with asbestosis and one with benign pulmonary disease, were chosen for comparison. A panel of miRNA including miR-16, miR-17, miR-21, miR-126 and miR-486 were evaluated. VEGF (vascular endothelial growth factor) was evaluated in plasma samples of patients with mesothelioma. Analysis of covariance (ANCOVA) followed by Bonferroni post-hoc test were used for multiple comparisons. P<0.05 was considered significant.
Results:
14 patients with malignant pleural mesothelioma, 14 patients with asbestosis and 21 patients with benign pulmonary disease were studied. The expression of miR-16 (p=0.018), miR-17 (p=0.024) and miR-126 (p=0.019) was significantly lower in patients with MPM compared with patients with benign pulmonary disease. Interestingly, miR-486 was able to discriminate patients with MPM compared to patients with asbestosis (p=0.004). Considering patients with MPM, miR-17 (p=0.023) and miR-486 (p=0.015) were significantly more expressed in patients with epithelial type than in patients with sarcomatoid and biphasic type. Moreover, the expression of miR-16 (p<0.0001), miR-17 (p<0.0001), miR-21 (p=0.004), miR-126 (p=0.0016) and miR-486 (p=0.003) was significantly lower in patients with asbestosis compared with subjects with benign pulmonary disease. In MPM plasma samples, VEGF expression was negatively correlated to miR-126 (p=0.004).
Conclusion:
The expression of miR-16, miR-17 and miR-126 was able to distinguish patients with MPM compared with patients with benign pulmonary diseases. miR-17 and miR-486 were significantly higher in patients with epithelial mesothelioma. An immunohistochemistry analysis evaluating the expression of VEGF in MPM tissue samples is ongoing. The available data support the role of miRNAs in the aetiology of MPM, suggesting their possible use as diagnostic markers of the disease.
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P2.03 - Poster Session/ Treatment of Locoregional Disease – NSCLC (ID 213)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.03-036 - Primary Pulmonary Large Cell Carcinoma with Syncytiotrophoblastic Aspect: Report of a Case (ID 2751)
09:30 - 09:30 | Author(s): P. Carbognani
- Abstract
Background:
To present the case of a primary large cell lung carcinoma with syncytiotrophoblastic aspect.
Methods:
A 54-year-old smoking man (60 pack/years), with no significant past medical history, presented for incidental radiological finding of a 5cm mass in the right middle lobe with partial invasion of the lower lobe (Fig.1). A PET/CT-scan showed a unique intense FDG-uptake of the pulmonary mass. A trans-thoracic fine-needle aspiration led to the diagnosis of non-small-cell lung cancer with sarcomatoid features. Preoperative cardiac and pulmonary function tests were normal. Figure 1
Results:
The patient underwent a right middle lobectomy and wedge resection of the lower lobe and radical lymphadenectomy through a posterolateral thoracotomy. The postoperative course was uneventful; the patient was discharged on the seventh postoperative day. After 52 months the patient is alive and disease-free. Macroscopically, the mass measured 5.5cm, had a greyish colour with lobulated margins. Microscopically, a poor differentiated tumor characterized by giant and medium pleomorphic cells sometimes with syncytial-trophoblastic features were observed (Fig.2a). Immunohistochemically, tumor cells were positive for beta-human-chorionic-gonadotrophin (Beta-HCG) (Fig.2b), anti-endomisium antibody (EMA), placental alkaline phosphatase (PLAP) e cytokeratin 7 (CK 7); the cells resulted negative for octamer-binding transcription factor-4 (OCT-4) (Fig.2c), spalt like transcription factor 4 (SALL4) (Fig.2d) and glypican-3. A subsequent genital examination and testicular ultrasonography excluded the presence of a primary gonadal choriocarcinoma. Beta-HCG serum levels were undetectable after surgery. Based on the above findings, a diagnosis of primary large cell lung carcinoma with syncytiotrophoblastic aspect was made. Final pathological stage was pT2aN0M0. No adjuvant therapy was proposed.Figure 1
Conclusion:
Large cell lung carcinoma with syncytiotrophoblastic aspect is an extremely rare finding. The prognosis is usually poor irrespective of the treatment; a few long-term survivors have been reported.
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P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.04-059 - Structural and Functional Characterization of the Hemolymphangiogenic Microenvironment in Lung Cancer (ID 919)
09:30 - 09:30 | Author(s): P. Carbognani
- Abstract
Background:
The hypothesis of the existence of a Lung Cancer Initiating Cell (LCIC) offers new pathogenetic and therapeutic options. CICs express vascular-related molecules in order to induce neoangiogenesis and establish an aberrant vascular niche. Conversely, tumor angiogenesis and formation of a cancer vascular niche contribute to the maintenance of CIC. The limited success of anti-angiogenic strategies in lung cancer imposes a better knowledge of the biology and architecture of the tumor vascular microenvironment. The aim of our study was to characterize the structural and functional changes of blood and lymphatic vasculature in human lung cancer.
Methods:
Fresh samples of the neoplastic (T) and spared distal (Dist) lung from 30 patients affected by NSCLC (21 Adeno and 9 Squamous) and 9 Neuroendocrine tumors were processed for immunohistochemical analysis and cell isolation. Control healthy lung (CTRL) was represented by 12 samples collected at autopsy from patients who died in the absence of respiratory diseases and 6 surgical specimens of pneumothorax. Immunofluorescence and confocal microscopy were employed using specific antibodies to detect blood (CD31, vWF, a-SMA) and lymphatic (Podoplanin Pdn, Lyve-1 and Prox-1) vessels. Moreover, the distribution of cells expressing stem/progenitor cell associated antigens (c-kit, CD133, CD34 and PDGFR) was assessed. Phenotypical and functional characterization on immunomagnetically sorted hematic (CD31[pos]) and lymphatic (CD31[pos]/Pdn[pos]) endothelial cells was performed on cells isolated from Dist and T lung samples.
Results:
Results indicated that, compared to CTRL capillary density increased by 77% and 74% in Dist and T portions of the lung, respectively. Conversely, the numerical incidence of venules did not show significant difference. These parameters were similarly represented in the three different tumor histotypes. A significant increase in arteriolar density was observed in all tumor types compared to CTRL. Moreover, the number of arterioles within T was increased by 3-fold compared to Dist portion. The quantitative analysis of lymphatic vessels showed similar values in all types of cancer specimens although rarefaction of these vascular structures was observed compared to CTRL. Moreover, lymphatic vessels density was 10-fold higher in Dist lung than in T. Immunofluorescence confocal analysis documented a positive gradient of c-kit[pos], CD34[pos] and PDGFR[pos] progenitor cells from Dist towards T in all cancer samples. However, compared to CTRL, cells expressing c-kit and CD34 were more numerous both in the Dist and T portion of the lung, while the increase in PDGFR[pos] cells was present only in T. Blood (BEC) and lymphatic (LEC) endothelial cells isolated from Dist and T samples of the lung, showed different growth properties and variable expression of Tumor Endothelial Marker (TEM) and receptor tyrosine kinases as VEGFR 2 and 3, PDGFRbeta, EGFR, IGF-1R, and c-met. Functional assays indicated that T derived LEC possess higher tube forming ability on matrigel than Dist LEC while this phenomenon was not observed in BEC. Moreover, wound healing assay showed a VEGF-C independent reduced migratory capacity of LEC isolated from T samples compared to the Dist counterpart.
Conclusion:
Specific changes in the composition and function of the tumor hemolymphangiogenic environment occur in lung cancer providing innovative pathogenetic and therapeutic approaches.
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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-114 - IASLC and WHO 2004 Grading System as Prognostic Factors in 492 Cases of Pulmonary Adenocarcinoma (ID 2647)
09:30 - 09:30 | Author(s): P. Carbognani
- Abstract
Background:
Primary aim of the study was to evaluate the prognostic value of the IASLC grading system and the WHO 2004 classification on a consecutive series of resected primary pulmonary adenocarcinomas. Secondary aim was to identify new prognostic histological features.
Methods:
All consecutive patients undergoing radical resection with a pathological diagnosis of primary lung adenocarcinoma were considered. All histological slides were reviewed for the study. Tumor-specific survival was considered as primary outcome. Statistical analysis included Kaplan-Meyer analysis and Cox regression to identify variables with significant Hazard Ratios (HR).
Results:
492 patients were considered between January 2002 and December 2013. 67.7% were male, mean age was 67.4 years, mean follow-up was 55 months. In a first multivariate Cox Regression Model the WHO 2004 grading was considered; gender [males vs females HR=1.7 95% CI (1.2-2.3), p=0.002], stage (p-trend <0.001), lymphoplasmacellular infiltrate [yes vs no HR=0.5 95% CI (0.3-0.8), p=0.001], and WHO 2004 grade (p-trend = 0.002) were independent prognostic factors of survival. In a second model the IASLC grading was considered; gender [HR=1.7 95% CI (1.2-2.4), p=0.002], stage (p-trend<0.001), lymphoplasmacellular infiltrate [HR=0.5 95% CI (0.3-0.8), p=0.001], and combined grading score according to Sica (p-trend=0.011) were maintained as independent prognostic factors.
Conclusion:
Tumor grading was an independent prognostic factor of survival in patients with adenocarcinoma undergoing lung resection both considering IASLC and WHO 2004 classifications. Lymphoplasmacellular infiltrate was significantly and favorably related to survival.
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P3.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 226)
- Event: WCLC 2015
- Type: Poster
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.08-028 - Primary Large Cell Neuroendocrine Carcinoma of the Mediastinum (ID 2780)
09:30 - 09:30 | Author(s): P. Carbognani
- Abstract
Background:
to present a rare case of primary neuroendocrine carcinoma of the mediastinum treated by multimodal therapy.
Methods:
a 50-year-old man, non-smoker, with unremarkable past medical history, presented for asthenia, dyspnea and sub-sternal discomfort. A chest CT-scan showed a huge mass of 10,7x5,5x9,5cm in the anterosuperior mediastinum. The mass seems infiltrate both brachiocephalic veins, the superior vena cava, pericardium and both lungs (Fig.1a/b). PET-CT showed an intense hyperactivity of the mediastinal mass. CT-guided needle biopsy allows diagnosis of neuroendocrine carcinoma. After multisciplinary discussion, a multimodal approach was planned. The patient underwent 4 cycles of chemotherapy with cisplatin and gemcitabine. Since chest CT-scan showed a reduction of the tumor (7,4x5,6x9cm), a surgical resection was proposed. Figure 1
Results:
a median sternotomy was performed. On exploration, both lungs were marginally infiltrated. The pericardium was partially excised; the left anonymous vein was almost totally invaded by the tumor. The right anonymous vein was infiltrated at the confluence with the superior vena cava. After total caval clamping (clamping time: 27’), a partial section and reconstruction with bovine pericardium was performed (Fig.1c). The patient was discharged uneventfully on postoperative-day 9. The patient underwent 25 sessions of adjuvant radiotherapy. Currently, he’s free of disease after 30 months. Macroscopically the mass measured 9x8x3cm, looks whitish with tense-elastic consistency. Microscopically it showed clusters of small uniform cells, sometimes with cuboidal morphology, with nuclear pleomorphism and small nucleoli, arranged in trabeculae, nests and lobules and immersed in a hyaline stroma with foci of necrosis (Fig.2a). Perineural and vascular invasion were present. Immunohistochemistry showed the tumor cells were positive for chromogranin (Fig.2c), synaptophysin (Fig.2d), cytokeratins and negative for TTF1, FAP, PSA. The proliferation index Ki-67 was 10% (Fig.2b). Considering the radiological, morphological and immunophenotypic characteristics, the diagnosis was consistent with primary neuroendocrine carcinoma of the mediastinum. Figure 1
Conclusion:
mid-term survival was achieved after aggressive multimodal therapy.
