Background MicroRNAs act as tumor suppressors or oncogenes. The pathological roles of miRNAs in gastric tumorigenesis are largely unknown. Although miR-10b was identified as an miRNA deregulator expressed in gastric cancer (GC), there also exists some debate on whether miR-10b is acting as tumor suppressor or oncogene in GC. Methods Quantitative RT-PCR was employed to investigate the level of miR-10b in GC tissues and matched adjacent normal tissues (n = 100). In vitro cell proliferation, apoptosis assays, cell migration, and invasion assays were performed to elucidate the biological effects of miR10b. Because silencing of miRNA by promoter CpG island methylation may be an important mechanism in tumorigenesis, GC cells were treated with 5-aza-2 0 -deoxycytidine and trichostatin A, and expression changes of miR-10b were subsequently examined by quantitative RT-PCR. Furthermore, the methylation status of the CpG island upstream of miR-10b was analyzed by methylation-specific PCR in GC tissues (n = 29). Results We showed here that miR-10b was significantly downregulated in GC cell lines and tissues as demonstrated by quantitative real-time PCR. Overexpression of miR-10b in MGC-803 and HGC-27 dramatically suppressed cell proliferation, migration, invasion, and induced apoptosis. Moreover, we demonstrated that T-cell lymphoma invasion and metastasis (Tiam1) was a target of miR-10b. Furthermore, 5-aza-2 0 -deoxycytidine and trichostain A increased miR-10b expression, and the methylation level was high in the CpG islands upstream of miR-10b gene. Conclusions Taken together, these findings suggest that miR-10b may function as a novel tumor suppressor and is partially silenced by DNA hypermethylation in GC.

Background & AimsGastric cancer is the most frequent gastrointestinal tumor in adults and is the most lethal form of human cancer. Despite of the improvements in treatments, the underlying mechanism of gastric carcinogenesis is not well known. To define novel modulators that regulate susceptibility to tumorgenesis, we focused on miR-219-2-3p.MethodsQuantitative RT-PCR was employed to investigate the level of miR-219-2-3p in gastric cancer (GC) tissues (n = 113) and their matched adjacent normal tissues (n = 113). In vitro cell proliferation, apoptosis assays, cell migration, and invasion assays were performed to elucidate biological effects of miR-219-2-3p. Since silencing of miRNA by promoter CpG island methylation may be an important mechanism in tumorgenesis, GC cells were treated with 5-aza-2′-deoxycytidine and trichostatin A, and expression changes of miR-219-2-3p were subsequently examined by quantitative RT-PCR. Finally, the methylation status of CpG island upstream of miR-219-2-3p was analyzed by methylation-specific PCR in GC tissues (n = 22).ResultsmiR-219-2-3p was down-regulated in GC and cell lines. In addition, the experiments documented the lower expression of miR-219-2-3p in GC specimens with higher grade and later stage tumors. Meanwhile, miR-219-2-3p exerted antiproliferative, proapoptotic, and antimetastatic roles and reduced levels of p-ERK1/2 in GC cells. Furthermore, 5-aza-2′-deoxycytidine and trichostatin A increased the expression (∼2 fold) of miR-219-2-3p in GC cells. By methylation-specific PCR, DNA methylation in the upstream region of miR-219-2-3p was detected in both adjacent normal tissues and cancer tissues. As expected, the methylation level was considerably higher in the miR-219-2-3p down-regulated group than up-regulated group.ConclusionsmiR-219-2-3p is potentially involved in gastric cancer progression and metastasis by regulating ERK1/2-related signal pathways, which may provide a novel therapeutic strategy for treatment of gastric cancer. Methylation mechanism may be involved in modulating the expression level of miR-219-2-3p in gastric cancer.

Background: The incidence of metachronous early cancer or precancerous lesions (MECPL) emerging at the anastomotic site (AS) after curative surgical resection of colorectal cancer (CRC) is so low that few study have been conducted to explore the clinical characteristics, diagnosis and treatment of these lesions.Endoscopic submucosal dissection (ESD) is technically difficult for these lesions because of the presence of severe fibrosis and AS. The aim of this study was to explore the safety and efficacy of ESD for MECPL emerging at the AS after curative surgical resection of CRC.Methods: The data used in the analysis were retrospectively collected from CICAMS in Beijing China between January 2013 and May 2019 and from all the patients who underwent ESD for MECPL emerging at the AS after curative surgical resection of CRC. The rates of en bloc resection (ER), complete resection (CR), curative resection (CuR) and incidence of complications were analyzed by SPSS software.Results: A total of 11 patients were included. The rates of ER, CR and CuR were 63.6%, 54.5% and 54.5%, respectively. No additional surgery was performed, and no recurrences were found. Bleeding occurred in only one case and there was no perforation after the operation.Conclusions: Overall, ESD is safe and effective in the treatment of MECPL emerging at the AS after curative surgical resection of CRC. Especially for patients with anastomotic recurrence close to anal margin, this method can avoid the risks of reoperation and improve the rate of anal preservation.

4572 Background: Human epidermal growth factor receptor 2 (HER2) overexpression is related to many tumor treatments. RC48-ADC, a novel humanized anti-HER2 antibody conjugated with monomethyl auristatin E, has shown a promising efficacy in patients with HER2-positive locally advanced or metastatic urothelial carcinoma (mUC). The characteristic expression and scoring systems of HER2 have existed in breast cancer, gastric cancer for many years, but not in UC. We aimed to explore the expression pattern of HER2 in UC and develop a validated HER2 scoring system. Methods: A total of 137 patients and 43 patients in two studies of cohort 1 and cohort 2 were enrolled, respectively. The patients of the cohort 2 were enrolled in the open-label, multicenter, phase II study of RC48-ADC. Formalin-fixed paraffin-embedded urothelial cancer samples were tested for HER2 status using the fluorescence in situ hybridization (FISH) PathVysion HER2 DNA probe kit (PathVysion, Abbott Molecular, USA). Immunohistochemistry (IHC) was performed using the Ventana Benchmark XT (Ventana Medical Systems, USA). The 2018 ASCO/CAP HER2 scoring system of breast cancer was adopted and modified to score HER2 expression level in UC. Results: The expression rate of HER2 (IHC 2+/3+) was 24.1% (33/137). In HER2 IHC status 3+ or 2+ patients, the HER2 amplified rate was 31% (13/42). The objective response rates in RC48-ADC treatment patients with IHC 3+, IHC 2+ and FISH +, IHC 2+ and FISH - were 58.8%, 66.7% and 40%, respectively. Heterogeneity of HER2 protein expression was 55.5% (15/27) and the objective response rate had no significant difference between patients with tumor heterogeneity and homogeneity. Conclusions: The modified HER2 testing scoring system could be applied to UC to determine which patient might benefit from anti-HER2-ADC treatment. There was a trend towards a better benefit for patients with HER2 amplification and the tumor heterogeneity did not influence the drug efficacy.

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e12584 Background: To investigate retrospectively the effect of non-sentinel lymph node status (non-SLN) on 10-year overall survival (OS) and non-SLN metastasis risk factors in patients with breast cancer and sentinel lymph node (SLN) metastasis. Methods: A large population (n = 15510) underwent SLN dissection in Cancer Hospital, Chinese Academy of Medical Sciences from 2011 to 2022. In total, 3033 (19.6%) cases had at least one SLN metastasis, which underwent axillary lymph node (ALN) dissection. The clinicopathological characteristics and their relationship with non-SLN status were analyzed. Among patients from 2011-2012(n = 132), the effect of non-SLN status on 10-year OS and disease-free survival (DFS) with SLN metastasis were also analyzed. Results: In 3033 patients with SLN metastasis, the mean age was (50.42±10.59) years. The average number of SLN metastasis in each patient was 1.75±1.21, the average number of SLN detected was 4.89±2.03 and the average number of ALN removed was 22.36±8.88. The number of SLN metastasis≥2 and positive lympho-vascular invasion were risk factors of non-SLN metastasis ( P< 0.05), but not the age, T stage and histological grade. In 132 patients from 2011-2012, a median follow-up of 9.1 years (interquartile range, 7.3-9.5 years), the non-SLN metastasis occurred in 60 cases (45.5%), DFS 70.8%, OS 85.9%; non-SLN non-metastasis occurred in 72 cases (54.5%), DFS 85.6%, OS 90.4%. There was no significant difference between two groups in DFS(χ² = 0.61, P = 0.43) and OS (χ² = 0.06, P = 0.81). Conclusions: The number of SLN metastasis≥2 and positive lympho-vascular invasion were risk factors of non-SLN metastasis. There were no significant differences between non-SLN metastasis group and non-metastasis group in DFS and OS.