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R. Sakakibara
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P1.07 - Poster Session with Presenters Present (ID 459)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.07-039 - Insulinoma-Associated 1 (INSM1) Immunohistochemical Expression in Lung Neuroendocrine Tumors (ID 5407)
14:30 - 14:30 | Author(s): R. Sakakibara
- Abstract
Background:
Insulinoma-associated 1 (INSM1) is a transcription factor, and expressed during early embryonal development. In vitro and in vivo, INSM1 has been reported to regulate the neuroendocrine differentiation pathway represented by achaete-scute complex homolog-like1 (ASCL1) and neuroendocrine molecules (CGA, SYP, CD56) in lung cancer. We examined association between INSM1 protein expression and clinicopathological characteristics in lung neuroendocrine tumors.
Methods:
Using 139 consecutive surgically resected cases of lung neuroendocrine tumor (78 small cell lung carcinomas [SCLCs], 42 large cell neuroendocrine carcinomas [LCNECs], and 19 carcinoids), we evaluated INSM1 and ASCL1 immunohistochemical expression, and examined the association of INSM1 and ASCL1 expression with clinicopathological features.
Results:
For the 78 SCLCs, male/female ratio was 3.9:1, age ranged 46-84 with a median of 67 years, average cumulative smoking was 50.6 (pack-years), and 60/78 (77%) were positive for any one of neuroendocrine molecules. For the 42 LCNECs, male/female ratio was 5:1, age ranged 42-84 years with a median of 70, and average smoking was 47.9. For the 19 carcinoids, male/female ratio was 0.73:1, age ranged 38-85 years with a median of 67, and average smoking was 21.9. All of SCLCs positive for neuroendocrine molecules (n=60) were positive for INSM1 (60/60) and 72% positive for ASCL1 (43/60). In the SCLCs negative for all neuroendocrine molecules (n=18), 72% were positive for INSM1 (13/18) and all of them were negative for ASCL1 (0/18). For LCNECs, 57% were positive for INSM1 (24/42) and 50% were positive for ASCL1 (21/42). All of the carcinoids were positive for INSM1 (19/19) and 53% of them were positive for ASCL1 (10/19). Taken together, INSM1 and ASCL1 were detectable in lung neuroendocrine tumors by immunohistochemistry in 83% (116/139) and 53% (74/139), respectively.
Conclusion:
Our study suggests INSM1 is a sensitive and useful neuroendocrine marker, even for SCLC without apparent expression of neuroendocrine markers.
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P2.01 - Poster Session with Presenters Present (ID 461)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.01-029 - Tumor B7-H3 (CD276) Protein Expression, Smoking History, and Survival in Lung Adenocarcinoma Patients (ID 4827)
14:30 - 14:30 | Author(s): R. Sakakibara
- Abstract
Background:
Compared with non-smoking counterparts, smoking-associated lung cancers is characterized by a high frequency of somatic mutations, including mutations of DNA repair genes, a high burden of neoantigens, and increased immunogenicity. B7-H3 (also known as CD276) belongs to a family of immune modulators that includes PD-1 and PD-L1 (also known as B7-H1 or CD274). Considering the better response to PD-L1 inhibitors in smokers’ lung cancer, we examined the prognostic interaction of tumor B7-H3 expression with smoking history in lung adenocarcinoma patients.
Methods:
Using tissue microarrays of consecutive 270 cases of lung adenocarcinoma, we evaluated tumor B7-H3 expression by immunohistochemistry. We examined the prognostic association of B7-H3 expression in strata of smoking history, using Cox proportional hazards regression analysis and the log-rank test. Additionally, we used logistic regression analysis to examine the correlations between B7-H3 expression levels and clinicopathological/molecular features of lung adenocarcinoma.
Results:
The association of B7-H3 expression with survival significantly indeed differed by smoking history (Pinteraction=0.014); B7-H3 high-expression was associated with inferior survival in moderate/heavy-smoking patients (smoking index [SI]≥400) (hazard ratio [HR]=3.07, 95% confidence interval [CI]=1.74-5.49, P=0.0001) (log-rank test: P<0.0001), but not in non/light-smoking patients (SI<400) (HR=2.24, 95% CI=0.63-1.96, P=0.64) (log-rank: P=0.64). High B7-H3 expression was associated with smoking patients (univariable odds ratio [OR]=2.63, 95 % CI=1.51-4.65, P=0.0005) and independently associated with EGFR wild-type status (multivariable OR=2.80, 95% CI=1.38-5.84, P=0.0042).
Conclusion:
We demonstrated that the prognostic association of B7-H3 expression indeed differed according to smoking history. The current study also showed significant association of high B7-H3 expression with EGFR wild-type and smoking patients, indicating the potential effectiveness of anti-B7-H3 therapy for EGFR wild-type or smokers’ lung adenocarcinoma.
