Virtual Library
Start Your Search
D. Moore
Author of
-
+
P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
-
+
P1.04-062 - Phagocytic Behaviour in Lung Adenocarcinoma Cells: Clinical Implications and Cellular Mechanisms (ID 2822)
09:30 - 09:30 | Author(s): D. Moore
- Abstract
Background:
Pulmonary adenocarcinoma is the commonest and the most histologically diverse form of lung cancer. ‘Cell-in-cell’ structures are frequently seen as incidental findings when making diagnoses of lung cancer. These structures arise when one viable tumour cell is enveloped within a vacuole within another viable tumour cell. They have been identified in a number of solid tumours including breast, lung, endometrial, pancreatic, melanoma and squamous cell carcinomas. The repeated occurrence of the phenomenon in such a range of tumour types suggests that it may represent a process that confers a selective advantage to the malignant clone (or subclone). Possible mechanisms for this include the acquisition of nutrition by the host cell, horizontal gene transfer, or simple clonal extinction of neighbouring subclones. The biological significance and mechanisms of action still all remain largely unknown. We set out to investigate these.
Methods:
100 recent consecutive cases of lung adenocarcinoma from our surgical centre were de-archived and examined. For each, high-resolution digital images of 10 high-power field (hpf) equivalents were examined. A scoring scheme for both cell-in-cell appearances and multinucleated cells was formulated and used to score the tumours. Independently from this they were classified by histological pattern and graded for numerous architectural and cytological characteristics. Results were collated and statistical tests carried out. In vitro experiments using cocultures of H1299 lung cancer cells transfected to express either GFP (Green Fluorescent Protein) or RFP (Red Fluorescent Protein) were also conducted. These cells were seeded on a selection of coated surfaces including gelatin, fibronectin and collagen to mimic the extracellular matrix proteins.
Results:
Cell-in-cell structures are frequently observed in primary lung adenocarcinomas. 15% of cases have frequent occurrences (≥0.8/hpf). Cell-in-cell structure frequently is strongly associated with multinucleation (P<0.0001). In addition, there is a strong association with cytological measures of tumour grade such as mitoses (P<0.0001), necrosis (P 0.015) and solid pattern (P=0.002). In cell co-culture experiments we are able to reproduce the same appearances, and to visualize cultured lung adenocarcinoma cells engulfing one another. The process is greatly enhanced by the presence of extracellular fibronectin or collagen, but gelatin has a negative effect. This suggests integrins may be involved in the process, as collagen and fibronectin are integrin activators, while gelatin is known for its lack of integrin activation.
Conclusion:
Lung adenocarcinomas frequently contain numerous cell-in-cell structures. This is related to the solid phenotype; this implies that engulfment requires full three-dimensional movement which is impossible in two-dimensional lepidic/acinar/papillary conformations. It is associated with high cytological grade, and may be a useful component of future grading systems. The association with multinuclearity implies that cell engulfment may be the mechanism that leads to the formation of multinucleated giant cells. The same appearances can be reproduced in cell culture systems, where they appear to be dependent upon the presence of signaling from the extracellular matrix.
