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Akihiko Yoshizawa
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P1.09 - Pathology (ID 173)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Pathology
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.09-18 - Small-Sized Spread Through Air Spaces (STAS) in Resected Pulmonary Adenocarcinoma: Is It Necessary to Record It as a Prognostic Factor? (ID 868)
09:45 - 18:00 | Presenting Author(s): Akihiko Yoshizawa
- Abstract
Background
Spread through air spaces (STAS) is a recently recognized invasive pattern of lung cancer that is a prognostic factor in patients who have undergone resection. It is histologically defined as “micropapillary clusters, solid nests, or single cells extending beyond the edge of the tumor into air spaces” in the 2015 World Health Organization classification of lung tumor fascicles; however, the prognostic significance of each pattern has not been studied well. This study evaluated their prognostic significance through a histological review of 1043 resected pulmonary adenocarcinoma (P-ADC) specimens.
Method
STAS was classified as follows: STAS 1, tumors with mainly small-sized clusters (1–3 tumor cells); STAS 2, tumors with mainly medium-sized clusters (4–20 typical micropapillary-pattern tumor cells); and STAS 3, tumors with large-sized clusters (>20 tumor cells). We recorded the STAS type of each specimen, analyzed its association with clinicopathological parameters, and assessed the prognostic significance of STAS in resected P-ADC specimens.
Result
Overall, 366 tumors (35.6%) were STAS positive, which was associated with male gender (P = 0.005), larger tumor size (P < 0.001), node metastasis (P < 0.001), lymphovascular and pleural invasion (all, P < 0.001), and higher stage (P < 0.001). The commonest type of STAS was STAS 2 (n = 262, 24.9% of all tumors), followed by STAS 3 (n = 69, 6.4% of all tumors) and STAS 1 (n = 28, 2.6% of all tumors). Patients with STAS-positive tumors had worse overall survival (OS) and disease-free survival (DFS) than patients with STAS-negative tumors (both P < 0.001). Patients with STAS 3 and STAS 2 tumors had worse prognosis than patients with STAS-negative tumors. However, there were prognostic differences between patients with STAS-negative tumors and those with STAS 1 tumors (log rank test, P = 0.764 for OS; P = 0.958 for DFS).
Conclusion
STAS is a strong prognostic factor; however, tumors with small-sized STAS (STAS 1) do not differ from tumors without STAS with respect to recurrence and mortality in patients with P-ADCs. This result may indicate that it is not necessary to record or recognize small-sized STAS as STAS.
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P2.03 - Biology (ID 162)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.03-09 - Arf6-Related Invasive Pathway Deteriorated Patients’ Prognosis in Mutant EGFR Lung Adenocarcinoma (ID 2937)
10:15 - 18:15 | Author(s): Akihiko Yoshizawa
- Abstract
Background
Arf6-related pathway has been reported to be activated in the downstream of EGF stimulation and to play pivotal roles in invadopodia formation and integrin recyclying leading to cancer invasion and metastasis. EGFR is well known to be constitutively activated without EGF stimulation in lung cancer harboring the mutations in its kinase domain. Here, we have examined the clinicopathological significance of Arf6-related pathway especially in mutant EGFR (mEGFR) lung adenocarcinomas.
Method
Clinical samples were obtained from the 239 cases of resected lung adenocarcinoma which were consecutively operated from January 2001 to December 2007 in Kyoto University Hospital. Then, tissue microarrays (TMAs) were made from all the cases. Using DNA samples extracted from fresh frozen tumors, EGFR mutations were detected by SSCP or direct sequencing methods as previouly published.
Immunohistochemical stainings were performed on TMAs against the molecules of Arf6-related pathway: Grb2, GEP100, Arf6, AMAP1, EPB41L5. The positivity of all molecules was judged according to their H-scores: intensities multiplied by percentages. Clinicopathological data were integrated and reviewed. Statistical analyses for overall (OS) or disease-free survival (DFS) were performed by Kaplan-Meirer methods and log-rank tests. Categorical data were analysed by Pearson’s test. Cox hazard models were applied for multivariate analyses. P-values less than 0.05 were considered significant.
Result
Among all cases, mEGFR was found in 113 cases, whereas 118 cases had wild type EGFR (wtEGFR) mutations. Common mutations in EGFR were detected in 104 cases (92.0%). Positivity of each molecule in mEGFR cases was the following: Grb2/ GEP100/ Arf6/ AMAP1/ EPB41L5; 11.9/ 27.7/ 48.2/ 52.7/ 56.3%. Positivity in all molecules showed no significant difference between exon 19 and exon21 mutation cases.
Visceral pleural involvments were significantly increased in AMAP1- or EPB41L5-positive groups and lymph node metastases were significantly increased in Grb2- or EPB41L5-positive groups.
Univariate analyses showed that 5-year OS rates were significantly low in Grb2 or AMAP1 positive groups specific to mEGFR cases (Grb2-/+: 89.0 vs 69.2%; p=0.0051, AMAP1-/+: 94.1 vs 80.3%; p=0.0057), whereas it was significantly low in EPB41L5 group specific to wtEGFR cases (-/+: 85.1 vs 62.7%; p=0.017).
For DFS, all molecules were the significant recurrent factors specific to mEGFR cases (Grb2/ GEP100/ Arf6/ AMAP1/ EPB41L5; p=0.0023/ 0.0033/ 0.0411/ 0.0023/ 0.0263), whereas no molecule was significant specifc to wtEGFR cases.
Multivariate analyses specific to mEGFR cases showed that Grb2 and AMAP1 were the independent prognostic factors for OS and Grb2 was the only independent recurrent factor.
Conclusion
Arf6-related invasive pathway was significantly associated with poor prognosis specific to mEGFR adenocarcinoma. Grb2 and AMAP1 were the strong worsening effectors on the prognosis. Inhibition of this pathway should be a novel targeted therapy in mEGFR lung adenocarcinoma.
