BackgroundHuman epidermal growth factor receptor 2 (HER2) is related to the pathogenesis and poor outcome of numerous types of carcinomas, including gastric carcinoma. Gastric cancer patients with HER2 positivity have become potential candidates for targeted therapy with trastuzumab.MethodsWe investigated 208 gastric cancer specimens using immunohistochemistry (IHC), fluorescence in situ hybridization and dual in situ hybridization (ISH). We also investigated the concordance between IHC and ISH. The correlation between HER2 status and various clinicopathological findings was also investigated. ResultsIn total, 15.9% (33/208) and 24.5% (51/208) of gastric cancers showed HER2 gene amplification and protein overexpression, respectively. A high level of concordance between ISH and IHC analyses (91.3%, κ = 0.76) was found. A significant correlation between HER2 status and intestinal-type (p < .05) and differentiated carcinomas (p < .05) was also noted. The HER2 heterogeneity was high in gastric cancers; we found 68.8% phenotypic heterogeneity and 57.6% genotypic heterogeneity. Heterogeneity in HER2 protein expression and gene amplification showed a close association with diffuse histologic type and IHC 2+. ConclusionsHER2 protein overexpression and gene amplification were detected in 24.5% and 15.9% of gastric cancer specimens, respectively. Intestinal-type showed a higher level of HER2 protein overexpression and gene amplification than diffuse type. HER2 status also showed a significant relationship with well- and moderately-differentiated carcinomas. The ratio of phenotypic and genotypic heterogeneity of HER2 was high in gastric carcinomas and was associated with HER2 IHC 2+ and diffuse histologic type.

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BackgroundGastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal neoplasms of the gastrointestinal tract. Management of GIST patients is currently based on clinicopathological features and associated genetic changes. However, the detailed characteristics and molecular genetic features of GISTs have not yet been described in the Vietnamese population.MethodsWe first identified 155 patients with primary GIST who underwent surgery with primary curative intent between 2011 and 2014 at University Medical Center at Ho Chi Minh City, Vietnam. We evaluated the clinicopathological features and immunohistochemical reactivity to p53 and Ki-67 in these patients. Additionally, KIT genotyping was performed in 100 cases.ResultsThe largest proportion of GISTs was classified as high-risk (43.2%). Of the 155 GISTs, 52 (33.5%) were positive for Ki-67, and 58 (37.4%) were positive for p53. The expression of Ki-67 and p53 were correlated with mitotic rate, tumor size, risk assessment, and tumor stage. Out of 100 GIST cases, KIT mutation was found in 68%, of which 62 (91.2%) were found in exon 11, two (2.9%) in exon 9, and four (5.8%) in exon 17. No mutation in exon 13 was identified. Additionally, KIT mutations did not correlate with any clinicopathological features.ConclusionsThe expression of Ki-67 and p53 were associated with high-risk tumors. Mutations in exon 11 were the most commonly found, followed by exon 17 and exon 9. Additionally, KIT mutation status was not correlated with any recognized clinicopathological features.

Background: Several lines of evidence have been focused on the roles of tryptophan metabolism genes like indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO2) in bladder cancer progression. However, the alternative way of targeting in cancer immunotherapy has been not yet investigated in bladder cancer. Method: We explored and validated the clinicopathological significance and the correlation with immune infiltrates of IDO1 and TDO2 expression in bladder cancer using Bladder urothelial carcinoma (BLCA) and other Gene Expression Omnibus (GEO) datasets (GSE13570, GSE31684, GSE48277) downloaded from https://xenabrowser.net/ and https://www.ncbi.nlm.nih.gov/geo/. The correlation between IDO1, TDO2 expression and the immune infiltrates as well as PD-L1 gene expression in BLCA dataset was explored with TIMER2.0, http://timer.comp-genomics.org/. Immunohistochemistry was performed to validate the relationship between TDO2 and PD-L1 expression in bladder cancer. Results: We figured out the IDO1 and TDO2 expressions were significantly upregulated in basal type compared with other molecular subtypes in BLCA. P53 mutations were associated with upregulation of IDO1 and TDO2 expression (p&lt;0.01) whereas FGFR3 mutation was associated with downregulation of IDO1 and TDO2 expression (p&lt;0.001). The overexpression of IDO1, TDO2 overexpression was significantly associated with advanced disease in BC. IDO1 and TDO2 expression were significantly correlated with purity and immune cell infiltrates, including T cells CD8+, T cells CD4+, B cells, neutrophils, and macrophages as wells as myeloid dendritic cells. Interestingly, TDO2 were positively correlated with cancer-associated fibroblasts (CAFs) (rho=0.5, p=1.14e-24). PD-L1 expression was also correlated with IDO1 (rho=0.64, p=4.42e-49) and TDO2 expression (rho=0.42, p=5.01e-19). Immunohistochemistry revealed the correlation between TDO2 and PD-L1 expression (p=0.011). Conclusion: Our results pointed out that IDO1 and TDO2 could play an essential role in regulating the tumor microenvironment as well as immune tolerance in bladder cancer. Suggesting that IDO1, TDO2 might be a promising novel immunotherapy target for bladder cancer patients. Citation Format: Quoc Thang Pham, Thanh Tu Nguyen, Thao Quyen Nguyen, Duc Tung Luu, Thi Nhu Diem Pham, Thi Thanh Tam Bui, Thanh Tu Duong, Dang Anh Thu Phan, Quoc Dat Ngo. Comprehensive analyzing the expression of IDO1 and TDO2 in bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5884.

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