Yifen Zhang

Expression of Lgr5 in human colorectal carcinogenesis and its potential correlation with β-catenin

Backgrounds and aimsLgr5 is a member of the G protein receptor super-family and was shown recently to be a stem cell marker for cells with intestinal differentiation. Its over-expression has been demonstrated in hepatocellular, basal cell carcinoma, and ovarian cancers but the underlying mechanisms are poorly understood. The aim of this study was to investigate if Lgr5 over-expression was correlated with human colorectal carcinogenesis and its potential correlation with β-catenin.MethodsThe study was carried out on a tissue microarray that consisted of 102 colorectal carcinomas (CRC; M:F = 55:47), 18 colon adenoma, and 12 colon normal mucosa cases. Immunostains were performed with the standard EnVision method with primary antibodies against Lgr5, β-catenin, and p53 antigens. Immunoreactivity of neoplastic cells to each antibody was double-blindly semi-quantified by two pathologists and the data were analyzed with the Chi-square and Spearman rank correlation tests. Subsequently, expression of Lgr5 in tissue sections of tumor centre and invasive margins of 21 cases of CRC certified to be immunoreactive of Lgr5 in TMA were evaluated and possible differences of Lgr5 expression between them were analyzed.ResultsLgr5 immunoreactivity was observed only in single cells in the base of normal colon mucosal crypts but high in 28% (five out of 18) adenomas, and significantly higher in 54% (55/102, p = 0.016) CRC cases. In normal mucosa, adenoma, and CRC, β-catenin expression was seen in 25% (three out of 12), 27% (five out of 18), and 81% (83/102) cases, respectively, in contrast to 0, 0, and 40% (41/102) for p53 expression, respectively. In CRC, Lgr5 expression was more intense in women than men (p < 0.0001), and positively correlated with β-catenin expression (p < 0.001), but not with patients’ ages, tumor sizes, nodal status, TNM stages, and p53 expression. Different expression of Lgr5 between tumor centre and invasive margins was not found (p > 0.05).ConclusionsThe results suggest that up-regulation of Lgr5 expression, especially in female patients, may play an important role in colorectal carcinogenesis, probably through the WNT/β-catenin pathway, but not involve the progression of the CRC.

Clinicopathological characterisation of small (2 cm or less) proximal and distal gastric carcinomas in a Chinese population

Summary Clinicopathological characteristics of small gastric carcinoma have not been well defined in Chinese patients. The aim of this study was to investigate and compare small proximal (PGC, n = 111) with distal (DGC, n = 202) gastric carcinoma in 313 consecutive surgically resected small (⩽2 cm) gastric carcinomas diagnosed with the WHO criteria. PGC patients were significantly older (average age 63 years versus 59 in DGCs) with a male/female ratio of 3:1. Most tumours were clustered along the lesser curvature (74% in PGCs and 65% in DGCs). Compared to DGCs, PGCs showed a protruded gross pattern significantly more frequently and were significantly better differentiated with a significantly wider histomorphological spectrum. Surprisingly, PGCs were composed of significantly fewer signet-ring cell carcinomas (1% versus 16% in DGCs) but were significantly more deeply invasive, compared to DGCs. Lymph node metastasis was detected in 23% overall, but was significantly less frequent in PGCs (16%) than in DGCs (26%) (p < 0.05). However, the difference in survival between the two groups was not statistically significant. Our results demonstrate that in Chinese patients, PGCs display distinct clinicopathological characteristics, compared to DGCs.

Differences in Clinicopathology of Early Gastric Carcinoma between Proximal and Distal Location in 438 Chinese Patients

Early gastric carcinoma (EGC) in Chinese patients remains poorly understood and endoscopic therapy has not been well established. Here, we compared endoscopic and clinicopathologic features between early proximal gastric carcinoma (PGC, n = 131) and distal gastric carcinoma (DGC, n = 307) in consecutive 438 EGCs diagnosed with the WHO criteria. By endoscopy, PGCs showed protruding and elevated patterns in 61.9%, while depressed and excavated patterns in 33.6%, which were significantly different from those (32.6% and 64.5%) in DGCs. PGCs were significantly smaller (1.9 cm in average, versus 2.2 cm in DGCs), invaded deeper (22.9% into SM2, versus 13% in DGCs), but had fewer (2.9%, versus 16.7% in DGCs) lymph node metastases. Papillary adenocarcinoma was significantly more frequent (32.1%, versus 12.1% in DGCs), as were mucinous and neuroendocrine carcinomas, carcinoma with lymphoid stroma (6.9%, versus 1.6% in DGCs); but poorly cohesive carcinoma was significantly less frequent (5.3%, versus 35.8% in DGCs). The overall 5-year survival rate was 92.9% in EGCs, and PGC patients showed shorter (42.4 months, versus 48.3 in DGCs) survival. Papillary and micropapillary adenocarcinomas and nodal metastasis were independent risk factors for worse survival in EGCs. EGCs in Chinese were heterogeneous with significant differences in endoscopy and clinicopathology between PGC and DGC.

Su1985 Unique Clinicopathologic Features of Early Proximal Gastric Cancer Diagnosed With Who Criteria: Implications for Endoscopic Resection

Introduction: Recent studies in the U.S. have reported steadily rising rates of cardia (CAR) gastric cancer, whereas rates of non-cardia (NCAR) gastric cancer have been declining. In addition, racial/ethnic disparities in CAR vs. NCAR gastric cancer exist, with significantly greater proportions of Asians having NCAR sub-types of cancer. Our study aims to evaluate disparate outcomes between CAR vs. NCAR gastric cancer, with a focus on identifying specific risk factors associated with these differences. Methods: Using data from California Pacific Medical Center, a tertiary referral center in northern California, we retrospectively analyzed adult patients with gastric cancer diagnosed from 2000-2012. Anatomic site-specific comparisons (CAR vs. NCAR cancers) were performed using chi-square testing for categorical variables and Students t-test for continuous variables. Long-term overall survival was evaluated using Kaplan Meier methods and log-rank testing. Overall 1, 3, and 5-year survival between CAR and NCAR cancers were stratified by sex, race/ethnicity, cancer stage, and histologic subtype. Multivariable Cox proportional hazards models were adjusted for age, sex, race/ethnicity, tobacco or alcohol use, cancer stage, treatment received, and anatomic site. Results: Overall, from 2000-2012 there were a total of 587 patients with gastric cancer (68.5% with NCAR and 31.5% with CAR). No significant difference in mean age of diagnosis was observed between NCAR and CAR cancers (69.3 +/0.7 vs. 67.1 +/0.9, p=0.076). While the majority of gastric cancer patients were white, there was significantly greater proportion of Asians in the NCAR cohort (39.3%, n=158). Compared to patients with NCAR cancers, significantly higher rates of tobacco use (35.8% vs. 52.6 %, p<0.001) and alcohol use (28.5% vs. 55.2%, p<0.001) were seen in CAR cancer patients. In addition, patients with NCAR cancers were more likely to be foreign born (79.4% vs. 51.4%, p=0.001). Overall 5-year survival was significantly higher among patients with NCAR cancers compared to CAR cancers (40.6% vs. 33.9%, p<0.001). However, after adjusting for multiple variables in a multivariate Cox proportional hazards model, the survival difference between NCAR and CAR gastric cancers was no longer significant (HR, 1.03; 95% CI, 0.76-1.39, p=0.87). Conclusions: Significant differences in demographics and clinical characteristics existed between NCAR and CAR gastric cancers. These differences may explain the significantly higher survival observed in patients with NCAR vs. CAR cancers. However, after adjusting for these differences in a multivariate regressionmodel, the survival advantage among patients with NCAR cancers was no longer present.

Micropapillary early gastric carcinoma with distinct Clinicopathologic features, high risk for lymph node metastasis, and dismal prognosis: a multicenter Clinicopathologic study of 29 cases identified in 1890 early gastric carcinoma radical Gastrectomies

Clinicopathology and risk factors of lymph node metastasis (LNM) in micropapillary early (pT1) gastric carcinoma (MEGC) remain elusive because of the extreme rarity. In this multicenter study, we investigated 1890 consecutive radical resections of early gastric carcinoma diagnosed with the World Health Organization criteria and identified 29 (1.5%) MEGC cases with a small (≥5%) micropapillary component. MEGC showed a male predominance (male-to-female ratio, 21:8). Most (93.1%; 27/29) tumors invaded submucosa. Lymphovascular invasion was detected in 14 (48.3%) of 29 cases. LNM was found in 13 cases (44.8%; 11 identified with a routine hematoxylin-eosin stain and 2 additional cases with a positive pancytokeratin immunostain). Overall, independent risk factors for LNM in early gastric carcinoma included patient age of 62 years or less, female sex, noncardiac location, ulcerative pattern, tumor size of greater than 2 cm, submucosal invasion, Lauren diffuse type, lymphovascular invasion, and MEGC. In MEGC, advanced pathologic stages were demonstrated in 6 (20.7%) of 29 cases. The 5-year overall survival rate of MEGC patients was 58.6%. Submucosal invasion, lymphovascular invasion, and LNM were significantly more frequent in the MEGC group than in the non-MEGC groups. Advanced pathologic stages were significantly more common in MEGC than in nonmicropapillary Lauren intestinal- but not diffuse-type early gastric carcinomas. In conclusion, MEGC demonstrated a high propensity for lymphovascular invasion, LNM with advanced stages, and dismal prognosis.