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Ryota Matsuoka
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P1.09 - Pathology (Not CME Accredited Session) (ID 941)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 2
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.09-16 - Novel Somatic Gene Mutation of SLC17A9, Detected in Early-Stage Lung Adenocarcinoma (ID 12518)
16:45 - 18:00 | Author(s): Ryota Matsuoka
- Abstract
Background
Lung adenocarcinoma is an example of a tumor that shows a wide range of mutations, such as EGFR, KRAS, ALK, ROS, and RET. However, with the exception of EGFR and KRAS, most mutations in lung adenocarcinoma have been detected in advanced tumors.
We have encountered one interesting case of multiple lung adenocarcinomas. The patient was a 68-year-old Japanese male in whom two tumors were detected in the left upper lobe and lobectomy was performed. One of which was diagnosed as lepidic adenocarcinoma and the other as minimally invasive adenocarcinoma (MIA). We considered that these two adenocarcinomas were synchronous and independent. Two years later, eight ground glass nodules were newly found in the left lower lobe. After chemotherapy, these tumors were also resected surgically, and all eight were found to show a lepidic pattern histologically. Moreover, two of the tumors were diagnosed as MIA. Therefore, it was very difficult to determine which of the tumors were multicentric and which were possibly metastatic from the previous adenocarcinoma.
In order to clarify the genetic background of these tumors, we examined the resected materials using next-generation sequencing.
a9ded1e5ce5d75814730bb4caaf49419 Method
We secured snap-frozen samples from one primary adenocarcinoma and two secondary adenocarcinomas. The DNAs were extracted and subjected to exome sequencing (Next-seq-500, Illumina). The mutations were validated by amplicon sequencing. Amplicon sequencing was also performed using DNAs extracted from FFPE blocks of the other tumors.
4c3880bb027f159e801041b1021e88e8 Result
From the exome sequences, 26, 365 and 308 mutations were detected from one primary tumor and two secondary tumors, respectively. Among these mutations, those of two genes, EGFR (L858R) and SLC17A9 (G78R), were detected as common mutations. This result was validated by amplicon sequencing of the same DNA. Amplicon analysis of the remaining 7 tumors revealed that all tumors had the same EGFR mutation, but that only 6 had the SLC17A9 mutation and one primary adenocarcinoma (MIA) lacked the mutation. These results indicated that the primary tumors were multicentric whereas the secondary tumors were metastatic from the primary lepidic adenocarcinoma.
8eea62084ca7e541d918e823422bd82e Conclusion
Our study of multiple early-stage adenocarcinomas and their metastases has revealed a common somatic mutation of SLC17A9 as well as EGFR mutation (L858R). SLC17A9 is a lysosomal ATP transporter that regulates cell viability. Although somatic mutation of SLC17A9 has not been reported previously in lung adenocarcinoma, SLC17A9 has been considered to have an oncogenic function. The present findings suggest that SLC17A9 gene alteration and its dysfunction may contribute to progression of lung adenocarcinoma.
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P1.09-30 - Heterotopic Expression of Ceruloplasmin in Lung Adenocarcinoma and its Possible Clinical Use as a Tumor Biomarker (ID 12100)
16:45 - 18:00 | Presenting Author(s): Ryota Matsuoka
- Abstract
Background
Ceruloplasmin (CP) is a well-known copper binding protein synthesized mainly in the liver, and its expression is well known to be elevated in the serum of cancer patients and in malignant tumor cells. Lung cancer is the leading cause of cancer-related death worldwide, and adenocarcinoma is the main histological type of lung cancer. Previously, we reported that the expression of CP mRNA was significantly higher in early but invasive adenocarcinoma than in adenocarcinoma in situ (AIS) on the basis of cDNA microarray analysis (Shiba, Int. J. Cancer 2011). However, the role of CP in lung adenocarcinoma is still unclear. Here, we examined and compared the expression of CP in various histological subtypes of lung adenocarcinoma and its correlation with patient outcome.
a9ded1e5ce5d75814730bb4caaf49419 Method
CP expression in resected specimens of lung adenocarcinoma and lung adenocarcinoma cell lines was determined using quantitative real-time RT-PCR and western blot analysis. Immunohistochemistry for CP was carried out using 196 specimens of lung adenocarcinoma and we divided the cases into a high expression group (H-score >90: 92 cases) and a low expression group (H-score <90: 104 cases).
4c3880bb027f159e801041b1021e88e8 Result
CP expression was significantly higher in invasive adenocarcinoma than in AIS. The high expression group had a significantly poorer outcome than the low expression group (p＜0.01) and high expression of CP was also correlated with pathological stage, pT, and pN (p＜0.01). Multivariate analysis showed that CP expression was an independent prognostic factor in lung adenocarcinoma patients (HR 1.642, 95％CI 1.050-2.568, p＝0.030). CP secreted from cancer cells was also detected by western blot analysis the medium used for culture of lung adenocarcinoma cell lines.
8eea62084ca7e541d918e823422bd82e Conclusion
CP is produced heterotopically by lung adenocarcinoma cells and its expression is associated with tumor progression. In view of the presence of the secreted form of CP in tumor cells, CP may be a useful biomarker for lung adenocarcinoma.
6f8b794f3246b0c1e1780bb4d4d5dc53
