[Clinicopathological and molecular characteristics of Epstein-Barr virus associated gastric cancer: a single center large sample case investigation].

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.

Quantitative analyses of epidermal growth factor receptors, HER-2/neu oncoprotein and cathepsin D in nonmalignant and malignant uteri.

BACKGROUND: Hormone receptors and oncoproteins are receiving increased attention as possible prognostic factors in different carcinomas. Few data are available regarding quantification of their levels of expression in gynecologic malignancies. METHODS: Epidermal growth factor (EGF) receptor specific binding capacities and affinities were measured by ligand binding assay using [125I]EGF in a competition mode with Accufit software (Lundon Software, Inc., Middlefield, OH). HER-2/neu oncoprotein was extracted from membranes and measured using an enzyme-linked immunosorbent assay. Cathepsin D was measured by an immunoradiometric assay using cytosols for steroid receptor analyses. RESULTS: EGF receptors in 23 nonmalignant uteri ranged from undetectable to 50 fmol/mg membrane protein (median, 0), with dissociation constant values of 1.2 x 10(-9) M to 8.5 x 10(-10) M, compared with EGF receptors in 76 endometrial cancers that ranged from undetectable to 7674 fmol/mg (median, 52). HER-2/neu oncoprotein ranged from undetectable to 2.9 HER-2/neu units (HNU)/microg protein (median, 0.6) in 41 nonmalignant uteri and from undetectable to 5.8 HNU/microg protein (median, 2.5) in endometrial cancers (n = 53). Cathepsin D ranged from 5 to 32 pmol/mg cytosol protein (median, 11) in 42 nonmalignant uteri and 18 to 144 pmol/mg protein (median, 42) in 29 endometrial cancers. CONCLUSIONS: Determination of the frequency and levels of EGF receptors, HER-2/neu protein, and cathepsin D in uteri with and without cancer and the availability of reference materials developed in our laboratory, will allow evaluation of their prognostic value in cancers of the uterus.

Expression of hormone receptors, cathepsin D, and HER-2/neu oncoprotein in normal colon and colonic disease.

BACKGROUND: Chronic ulcerative colitis and familial adenomatous polyposis are associated with an increased risk of colorectal carcinoma. Currently, there are no reliable methods to assess carcinoma risk. METHODS: Several prognostic factors known to be useful in breast carcinoma were determined in 102 specimens of colonic mucosa from 38 patients: 22 specimens from "normal," non-neoplastic colon, 49 from chronic ulcerative colitis, 10 from Crohn's colitis, 14 from familial adenomatous polyposis, four from mucosa adjacent to carcinoma, and three from colon carcinoma. Expression of estrogen receptor, progestin receptor, epidermal growth factor receptor, HER-2/neu (c-erb B-2) oncoprotein, and cathepsin D were determined. RESULTS: Epidermal growth factor receptor expression was higher in chronic ulcerative colitis, Crohn's colitis, familial adenomatous polyposis, and colon carcinoma and varied with location within the colon for chronic ulcerative colitis, Crohn's colitis, and familial adenomatous polyposis. Epidermal growth factor receptor expression in mucosa adjacent to carcinoma was similar to that in "normal" colon. CONCLUSION: Further analyses are needed to determine which parameters are related to and possibly predictive of increased carcinoma risk.