We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) 1-3 of esophageal squamous cell carcinoma (ESCC) in ethnic Chinese (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study, and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% CI 0.82-0.88; P=7.72x10−20) and rs1642764 at 17p13.1 (per-allele OR= 0.88, 95% CI 0.85-0.91; P=3.10x10−13). rs7447927 is a synonymous single nucleotide polymorphism (SNP) in TMEM173 and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR=1.33, 95% CI 1.22-1.46; P=1.99x10−10). Our joint analysis identified new ESCC susceptibility loci overall as well as a new locus unique to the ESCC high risk Taihang Mountain region.

We aimed to investigate the immunophenotype, differential diagnosis, and clinicopathological characteristics of signet-ring cell carcinoma (SRCC) derived from gastric foveolar epithelium.Methods: Clinical characteristics, endoscopic findings, histopathological features, and follow-up data of seven cases of SRCC derived from gastric foveolar epithelium with small intramucosal lesions were analyzed.Results: Seven patients with a mean age of 38.3 years were diagnosed with SRCC derived from gastric foveolar epithelium and small intramucosal lesions, all of them were negative for CDH-1 germline mutation. The glands proliferated and expanded, and then morphologically transformed into signet-ring cells and formed clonal hyperplastic SRCC, which expanded laterally along the gastric foveolar cells to a length of 3-6 mm. Periodic acid Schiff staining was positive, while CK7 and MUC6 were negative, in all cases. Ki-67-positive cells ranged 37%-60%. During a follow-up period of 6-30 months, no patients experienced tumor recurrence or metastasis.Conclusions: SRCC derived from gastric foveolar epithelium is originated from the proliferative region of the bottom of the gastric pit and gland neck. It is easily missed diagnosed or misdiagnosed as it grows laterally along the gastric foveolar cells. Biological behavior, genetics, and etiology of such SRCC, as well as the clinicopathological characteristics, need to be further studied.

Background Increasing evidence has highlighted the role of ubiquitin-like PHD and RING finger domain-containing protein 1 (UHRF1) in the development of cancers, including hepatocellular carcinoma, pancreatic cancer, and bladder cancer. However, the correlation between UHRF1 and breast cancer remains unclear. The present study aimed to analyze the expression of UHRF1 and its role in the development of invasive ductal breast cancer (IDC) by integrating multilevel expression data and immunohistochemistry analysis. Methods The Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were used to gather UHRF1 expression data on IDC. Additionally, immunohistochemistry analysis was used to investigate the correlations between UHRF1 expression and the clinical characteristics of IDC. Results The GEO and TCGA databases indicated that UHRF1 was up-regulated in IDC. Consistently, the immunohistochemical specimens showed that the significant overexpression of UHRF1 in IDC, and its expression level showed an increasing trend from ductal carcinomas in situ to IDC. Notably, the increased levels of UHRF1 were closely correlated with estrogen receptor expression, pathological grade, and the prognosis of the disease. In addition, patients with a high UHRF1 expression had a poorer prognosis. Conclusions In conclusion, our findings suggested that UHRF1 plays a promoting role in breast tumorigenesis, and the over-expression of UHRF1 could serve as a biomarker for the prognosis in invasive ductal carcinomas in breast cancer.

Background:To investigate the clinicopathological characteristics, immunophenotype and differential diagnosis of signet-ring cell carcinoma of gastric pit epithelium. Methods Seven cases of signet-ring cell carcinoma of gastric pit epithelium were studied by histomorphology observation, special staining, immunohistochemical staining and follow-up. Results At the initial stage, the glands proliferated and expanded, and the cells morphologically transformed into signet ring-like atypical cells and then formed clonal hyperplastic signet-ring cell carcinoma, which expanded laterally along the gastric pit, with a length of 3–6 mm. Erosion or mucosal ulcers can be formed on the surface, and the atrophy of fundus or pylorus glands leads to local depression of gastric mucosa. PAS was positive by special staining. Immunophenotype testing included MUC5AC, CKpan, CK20, CEA, villin and CDX2 with positive expression. In cytology, five cell morphologies could be seen: classic, immature, high proliferation, non-nucleus vacuole and degeneration. Three out of seven cases were accompanied by Helicobacter pylori (Hp) infection, accounting for 42.9% of the cases. Conclusion The signet-ring cell carcinoma of gastric pit epithelium originates from the proliferative region of the gastric fundus and the neck of gastric gland, which grows laterally along the gastric pit and is easy to be missed and misdiagnosed. Attention should be paid to the differential diagnosis, and the recognition level of signet-ring cell carcinoma of gastric pit epithelium should be improved.

ObjectiveThe present study aimed to investigate the histopathological types and distribution characteristics of gastric mixed tumors.MethodsDetailed histological observations, together with related immunohistochemical and genetic tests, were analyzed on 960 surgically resected samples in 6 hospitals with gastric mixed tumors from May 2017 to May 2021 in this retrospective study.ResultsEpithelial-derived tumors accounted for 80.10% (769/960) of the gastric mixed tumor samples studied, and tumors of different tissue origins accounting for 10.83% (104/960), mesenchymal-derived tumors accounting for 6.25% (60/960), neuroendocrine tumors accounting for 2.40% (23/960), and lymphoma accounting for 0.42% (4/960). The histological types of gastric mixed tumors identified as most commonly were epithelial originated, followed by mixed tumors of different tissue originated, then mixed neuroendocrine, lymphoma, and mesenchymal originated in sequence. The histological number of gastric mixed tumors was ≤ 3 in 83.23% (799/960) of cases and > 4 in 16.77% (161/960) of cases. The mixed histological patterns of gastric mixed tumors were divided into three types: those with tumor cells interspersed with each other, those with incomplete fibrous tissue separation, and those without fibrous tissue separation. The gene target characteristics of gastric mixed tumors were the existence of multi-gene mutation, including human epidermalgrowth factor receptor-2 (HER2) gene amplification, key result areas (K-ras) and platelet-derived growth factor receptor alpha (PDGFRA).ConclusionGastric mixed tumors should be adequately sampled, each piece of tissue should be involved in the morphological proportional division of the tumor, and any independent histological component should be written into the pathological examination report.