Clinicopathological and molecular characteristics of Epstein-Barr virus associated gastric cancer: a single center large sample case investigation / 北京大学学报(医学版)

OBJECTIVE@#Epstein-Barr virus associated gastric cancer (EBVaGC) is different from the traditional gastric cancer (Epstein-Barr virus non-associated gastric cancer, EBVnGC), and has unique clinicopathological features. This study investigated the largest single center cancer series so as to establish the clinicopathological and molecular characteristics of EBVaGC in China.@*METHODS@#A retrospective analysis was conducted on EBVaGC and EBVnGC patients diagnosed at Peking University Cancer Hospital from 2003 to 2018 by comparing their clinicopathological features and prognosis. The gastric cancer (GC) dataset of public database was analyzed to obtain differentially expressed genes. The expression of important genes and their association with prognosis of GC were verified in GC tissues from our hospital.@*RESULTS@#In this study, 3 241 GC patients were included, and a total of 163 EBVaGC (5.0%) patients were identified. Compared with EBVnGC, EBVaGC was higher in male and younger patients, and positively associated with remnant GC, poorly differentiated adenocarcinoma, and mixed type GC. EBVaGC was inversely related to lymph node metastasis. The 5-year survival rate of EBVnGC and EBVaGC was 59.6% and 63.2% respectively (P<0.05). In order to explore molecular features of EBVaGC, the Cancer Genome Atlas (TCGA) dataset was analyzed (n=240), and 7 404 significant differentially expressed genes were obtained, involving cell proliferation, apoptosis, invasion and metastasis. The down-regulated invasion/metastasis gene SALL4 and the up-regulated immune checkpoint gene PD-L1 were important molecular features of EBVaGC. Validation of these two genes in large GC series showed that the majority of the EBVaGC was SALL4 negative (1/92, 1.1%, lower than EBVnGC, 303/1 727, 17.5%), and that PD-L1 was mostly positive in EBVaGC (81/110, 73.6%, higher than EBVnGC, 649/2 350, 27.6%). GC patients with SALL4 negative and PD-L1 positive were often associated with better prognosis.@*CONCLUSION@#EBVaGC is a unique subtype of GC with less metastasis and a good prognosis. It also has a distinct molecular background. The down-regulation of invasion/metastasis gene SALL4 and up-regulation of immune checkpoint gene PD-L1 are important molecular features.

Gastric neuroendocrine carcinoma and gastric carcinoma with neuroendocrine cell differentiation: a clinical and prognostic analysis / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathological features, treatment, and prognosis of gastric neuroendocrine carcinoma and gastric carcinoma with neuroendocrine cell differentiation.</p><p><b>METHODS</b>A total of 19 patients were treated for gastric neuroendocrine cancer or gastric cancer with neuroendocrine differentiation in the Beijing Cancer Hospital from January 1997 to December 2008. Clinical data were retrospectively analyzed.</p><p><b>RESULTS</b>Fourteen patients had neuroendocrine carcinoma in the gastric cardia (n=9) or gastric body(n=5), and 5 patients had gastric cancer with neuroendocrine differentiation in the gastric cardia(n=2), the antrum(n=2), and the entire stomach(n=1). According to the International Classification of Disease for Oncology(2000), patients were divided into gastric carcinoid type I((n=2, 10.5%), type III( sporadic gastric carcinoid (n=9, 47.4%), small cell carcinoma of the stomach(n=3,15.8%), and gastric cancer with neuroendocrine cell differentiation(n=5, 26.3%). Clinical manifestations were mostly non-specific. Diagnosis was based on pathological and immunohistochemical examination. Eighteen patients underwent surgery including radical subtotal gastrectomy and total gastrectomy, of whom 3 underwent simultaneous resection of the liver metastasis. The remaining one patient with small cell carcinoma of the gastric body received chemotherapy alone because of unresectable liver metastasis. The survival rate was 73.7% at 1 year and 38.6% at 3 years.</p><p><b>CONCLUSIONS</b>Gastric neuroendocrine carcinoma usually develops in the cardia and body of the stomach. Gastric carcinoma with neuroendocrine cell differentiation can occur in any locations of the stomach. Immunohistochemistry is important to the diagnosis. Radical resection is the main treatment.</p>

Expression of human epidermal growth factor receptor 2 in gastroesophageal cancer with different scoring systems and its relationship with clinicopathological features / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To compare the expression of human epidermal growth factor receptor 2 (HER2) under different scoring systems in gastroesophageal cancer and its relationship with clinicopathological features.</p><p><b>METHODS</b>Clinicopathological data were retrospectively reviewed of 127 patients with gastroesophageal cancer between January and December 2009 in the Department of Surgery at the Cancer Hospital of Peking University. Tumor specimens were collected. The expression of HER2 protein was detected by immunohistochemistry.</p><p><b>RESULTS</b>HER2 positive rate(++/+++) in gastroesophageal cancer was 15.0%(19/127) with both new and traditional immunohistochemical scoring systems, while HER2 strong positive rate(+++) was 10.2%(13/127) and 6.3%(8/127), respectively(P=0.26). Univariate analysis showed that the expression rate of HER2 protein was associated with differentiation and Lauren classification of the tumor. Multivariable analysis showed that TNM staging and tumor differentiation were independently associated with the expression of HER2 protein(both P<0.05).</p><p><b>CONCLUSIONS</b>There is no change in HER2 positive rate in gastroesophageal cancer between the new and traditional immunohistochemical scoring systems. Expression of HER2 is associated with clinicopathological features in the gastroesophageal cancer.</p>