Gastric-and intestinal-type marker expression in invasive ductal adenocarcinoma of the pancreas

BACKGROUND:Although invasive ductal adenocarcinoma of the pancreas(PDAC) manifests as a relatively uniform histomorphological feature of the pancreatobiliary type,it may be complicated by metaplastic changes and heterogeneous gastric and intestinal elements.This study aimed to investigate the complication rate and clinicopathological significance of such heterogeneous elements.METHODS:Fifty-nine patients who underwent resection of PDAC were examined in this study.Immunohistochemically,tumors showing high expression(>25%) of the intestinal-type(INT) marker CDX2 were classified as PDAC with INT.Those with high expression(>25%) of the gastric-type(GAS) marker MUC5AC were classified as PDAC with GAS,while those with high expression of both markers were classified as PDAC with INT/GAS.These patients were compared with those with PDAC of the negative group in which neither markers was highly expressed to examine their clinicopathological significance.RESULTS:In the 59 patients,31(52.5%) showed high CDX2 or MUC5AC expression.Twenty-eight patients(47.5%) belonged to a negative group,11(18.6%) to a PDAC with INT group,15(25.4%) to a PDAC with GAS group,and 5(8.5%) to a PDAC with INT/GAS group.No significant differences were observed for age,gender,size,localization,T classification,or prognosis among the four groups.Although the PDAC with GAS group had well differentiated types significantly more than the other groups,the rate of lymph node metastasis in this group was significantly higher(PDAC with GAS:73%;other groups:36%).CONCLUSION:Complications with heterogeneous elements are not uncommon in PDAC,and this should be considered during the diagnosis and treatment of PDAC along with histogenesis of the disease.

Casein kinase 2 interacting protein 1 positively regulates caudal-related homeobox 1 in intestinal-type gastric cancer

Background:Gastric cancer(GC)is one of the most common malignancies,and intestinal-type GC is the main histopathologic type of GC in China.We previously reported that casein kinase 2 interacting protein 1(CKIP-1)acts as a candidate tumor suppressor in intestinal-type GC.CKIP-1 participates in the regulation of multiple signaling pathways,including the Wnt/b-catenin pathway,of which caudal-related homeobox 1(CDX1)may be a downstream target gene.The purpose of this study was to investigate the relationship between CKIP-1 and CDX1 in intestinal-type GC.Methods:Sixty-seven gastroscopy biopsy specimens and surgically resected gastric specimens were divided into four groups:gastric mucosa group,intestinal metaplasia(IM)group,dysplasia group,and intestinal-type GC group.The expression levels of CKIP-1 and CDX1 were detected in these groups and GC cell lines,and the correlations between these expression levels were analyzed.SGC7901 and BGC823 cells were divided into CKIP-1 shRNA groups and CKIP-1 over-expression groups,and CDX1 expression was detected.b-Catenin expression was detected in intestinal-type GC tissue samples and CKIP-1 shRNA and CKIP-1 overexpression SGC7901 cells,and its correlation with CKIP-1 expression in intestinal-type GC tissue was analyzed.The Wnt/b-catenin pathway inhibitor DKK-1 and activator LiCl were incubated with SGC7901 cells,BGC823 cells,and CKIP-1 shRNA and CKIP-1 over-expression SGC7901 and BGC823 cells,following which CDX1 and Ki-67 expression were detected.Results:The expression levels of CKIP-1 and CDX1 were lower in patients with intestinal-type GC than in patients with IM and dysplasia(both P<0.05).CKIP-1 and CDX1 expression levels were positively correlated in IM,dysplasia,and intestinal-type GC tissue and cell lines(r=0.771,P<0.01;r=0.597,P<0.01;r=0.654,P<0.01;r=0.811,P<0.01,respectively).CDX1 expression was decreased in the CKIP-1 shRNA groups and increased in the CKIP-1 over-expression groups of SGC7901 and BGC823 cells compared to that in the corresponding control groups(both P<0.05).CKIP-1 expression was negatively correlated with b-catenin expression in intestinal-typeGCpatients(r=0.458,P<0.01).Compared to the control group,b-catenin expression was increased in the CKIP-1 shRNA SGC7901 cell group and decreased in the CKIP-1 over-expression SGC7901 cell group(P<0.05).CDX1 expression was increased inSGC7901 andBGC823 cells treatedwithDKK-1,DKK-1 increasedCDX1 expression and decreased Ki-67 expression in the CKIP-1 shRNA group;the opposite result was observed in SGC7901 and BGC823 cells treated with LiCl,and LiCl decreased CDX1 expression and increased Ki-67 expression in the CKIP-1 over-expression group(both P<0.05).Conclusions:Through the Wnt/b-catenin signaling pathway,CKIP-1 may positively regulate CDX1 in intestinal-type GC.

Prognostic and pathological impact of tumor budding in gastric cancer: A systematic review and meta-analysis

BACKGROUND Tumor budding,is a promising prognostic hallmark in many cancers,and can help us better assess the degree of malignancy in gastric cancer(GC)and in colorectal cancer.In the past few years,several articles on the relationship between tumor budding and GC have been published,but different results have been observed.As the relationship between tumor budding and GC remains controversial,we integrated the data from 7 eligible studies to conduct a systematic review and meta-analysis.AIM To systematically evaluate the prognostic and pathological impact of tumor budding in GC.METHODS Literature searches were conducted in the PubMed,Cochrane Library,EMBASE and Web of Science databases,and 7 cohort studies involving 2178 patients met our criteria and included in the analysis.The patients were divided into those with high-grade tumor budding and those with low-grade tumor budding,and the cut-off values for tumor budding varied across the included studies.The hazard ratios(HRs)with 95%confidence intervals(CIs)were calculated to estimate the impact of tumor budding on overall survival(OS)in GC patients.The odds ratios(ORs)with 95%CIs were used to determine the correlation between tumor budding and pathological parameters(tumor stage,tumor differentiation,lymphovascular invasion,lymph node metastasis)of GC.RESULTS Seven studies involving 2178 patients were included in the meta-analysis.The combined ORs suggested that high-grade tumor budding was significantly associated with tumor stage(OR=6.63,95%CI:4.01-10.98,P<0.01),tumor differentiation(OR=3.74,95%CI:2.68-5.22,P<0.01),lymphovascular invasion(OR=7.85,95%CI:5.04-12.21,P<0.01),and lymph node metastasis(OR=5.75,95%CI:3.20-10.32,P<0.01).Moreover,high-grade tumor budding predicted a poor 5-year OS(HR=1.79,95%CI:1.53-2.05,P<0.01)in patients with GC and an adverse 5-year OS(HR=1.93,95%CI:1.45-2.42,P<0.01)in patients with intestinal-type GC.CONCLUSION High-grade tumor budding suggested a poor prognosis in patients with GC or intestinal-type GC.

Youngest case of an early gastric cancer after successful eradication therapy

A 28-year-old woman visited our clinic with a chief complaint of epigastralgia. She had received successful Helicobacter pylori (H. pylori ) eradication therapy 5 years before. We repeated esophagogastroduodenoscopy, and a discolored depressed area with reddish spots and converging folds, 20 mm in size, was detected. No atrophic change including intestinal metaplasia or nodular gastritis was seen endoscopically. Two endoscopic biopsies revealed undifferentiated adenocarcinoma. No H. pylori was found, and the 13 C-urea breath test was also negative. Abdominal computed tomography demonstrated no nodal involvement, distant metastasis or fluid collection. She underwent a laparoscopyassisted distal gastrectomy. Histologically, the resected specimen revealed an early undifferentiated gastric cancer that had invaded deeply into the submucosal layer. Nodal involvement was histologically confirmed.No atrophic change or H. pylori infection was evident histologically. This is the youngest patient ever reported to have developed a node-positive early gastric cancer after eradication of H. pylori .

Intestinal type gastric adenocarcinoma with unusual synchronous metastases to the colorectum and bladder

A 75-year-old male presented with difficult defecationand increasing urinary frequency over a few months. He had a significant history of previous partial gastrectomy for gastric carcinoma 20 years prior. Computed tomography of the abdomen and pelvis showed extensive lymphadenopathy, a gastric mass and rectal as well as bladder wall thickening with bilateral ureterohydronephrosis. Normal looking serosal surfaces of the bladder and bowel were seen on laparoscopy and a defunctioning ileostomy was created. Gastroscopy revealed a malignant mass while cystoscopy and sigmoidscopy found extensive tumour growth lining the mucosal surfaces. Biopsies from all sites were compatible with intestinal type adenocarcinoma of gastric origin with few signet ring cells. Metabolic response to palliative chemotherapy was good and the patient's symptoms have improved on follow-up four months post ileostomy. We discuss the immunohistochemical profile of the tumour and review the literature.