OBJECTIVE: IKAROS family zinc finger 3 (IKZF3) is an oncogene involved in different malignancies, particularly in the development and malignant progression of lymphocytes. However, IKZF3 amplification and clinical significance in gastric cancers (GCs) remain unexplored.
METHODS: We examined IKZF3 amplification status in 404 GCs with HER2 amplification status using tissue microarray (TMA) and fluorescence in situ hybridization (FISH) assays.
RESULTS: IKZF3 amplification was detected in 6.9% (28/404) of all GC patients, with higher rates in intestinal-type gastric cancer (IGC) (11.22%, 22/196) compared to other types (2.88%, 6/208). HER2 amplification was identified in 16.09% (65/404) of all GC patients, with higher rates in IGC (20.92%, 41/196) compared to other types (11.54%, 24/208). Co-amplification of IKZF3 and HER2 was detected in 8.16% (16/196) of IGC patients and in 2.40% (5/208) of other types. IKZF3 amplification showed significant correlation with IGC (P = 0.001) and HER2 amplification (P = 0.0001). IKZF3 amplification exhibited significantly worse disease-free survival (DFS) (P = 0.014) and overall survival (OS) (P = 0.018) in GC patients, particularly in IGC (DFS: P < 0.001; OS: P < 0.001), rather than other types. Cox regression analysis demonstrate IKZF3 amplification as an independent poor prognostic factor in all GCs (P = 0.006, P = 0.004 respectively) and in IGC patients, regardless of stages I-II or III-IV (P = 0.007, P = 0.004 respectively). On the other hand, HER2 amplification was significantly associated with worse DFS (P = 0.008) and OS (P = 0.01) in IGC patients, but not in all GCs and in multivariate analysis. Within the subset of patients with HER2 amplification, those also exhibiting IKZF3 amplification displayed potential poorer prognosis (P = 0.08, P = 0.11 respectively).
CONCLUSIONS: IKZF3 amplification was detected in minority of GC patients, especially in IGC, and was an independent indicator of poor prognosis. Our study, for the first time, found the prognostic value of IKZF3 was superior to HER2 for GC patients.

Despite its histological resemblance to colorectal adenocarcinoma, there is little information about the molecular events involved in the pathogenesis of intestinal-type sinonasal adenocarcinoma (ITAC). The present study investigated the possible role and clinical value of microRNA (miR)-let-7a, a head and neck squamous cell carcinoma-related miR, in a well-characterized and homogeneous cohort of patients with ethmoidal ITAC associated with occupational exposure, treated by primary surgery. miR-let-7a expression levels were analyzed in 23 pairs of ethmoidal ITAC and adjacent normal formalin-fixed paraffin-embedded tissues by reverse transcription-quantitative PCR. The expression was evaluated in tumor and healthy tissues according to: Tumor grade (G) of differentiation and extension, and pTNM stage, and presence/absence of recurrence. Comparisons within and between groups were performed using two-tailed Student\'s paired t-test and one-way ANOVA with Tukey\'s post hoc test. P<0.05 was considered to indicate a statistically significant difference. miR-let-7a expression in ethmoidal ITAC tissues was significantly lower than that in adjacent normal tissues (P<0.05; mean expression level ± SD, 1.452707±1.4367189 vs. 4.094017±2.7465375). miR expression varied with pT stage. miR-let-7a was downregulated (P<0.05) in advanced stages (pT3-pT4) compared with earlier stages (pT1-pT2). Furthermore, downregulation of miR-let-7a in ITAC was associated with poorly-differentiated (G3) cancer (P<0.05). No other associations were observed between miR-let-7a expression and the other clinicopathological parameters, including disease-free survival. In conclusion, downregulation of miR-let-7a in ITAC was associated with advanced-stage (pT3 and pT4) and poorly-differentiated (G3) disease, suggesting that the mutation of this gene, combined with additional genetic events, could serve a role in ITAC pathogenesis.

Colorectal clear cell adenocarcinomas are rare tumors. They can be divided into two types: intestinal- and Müllerian-type. Most intestinal-type clear cell adenocarcinomas show a composite morphology, and most early-stage (T1) intestinal-type clear cell adenocarcinomas have an adenoma component. We report an additional early-stage (T1) colonic clear cell adenocarcinoma that was a de novo adenocarcinoma without any adenoma component. It had a pure morphology and the smallest size (0.6 cm) ever reported. Immunohistochemical results demonstrated an intestinal phenotype (KRT20+, KRT7-, CEA+, and CDX2+). Periodic acid-schiff and alcian blue stains were both negative, which demonstrated decrease in mucin expression in the clear tumor cells. Enteroblastic differentiation was observed in a few colorectal clear cell adenocarcinomas in the literature, while it had not been observed in the present tumor. The tumor did not have deep submucosal invasion and cancer embolus, endoscopic submucosal dissection with regular follow-up was an appropriate treatment for the patient. Due to the rarity and diversity of primary colorectal clear cell adenocarcinomas, the cause of clear cytoplasm change and the impact on patient prognosis remain unknown. Accumulating evidence indicates that clear cell adenocarcinomas of intestinal-type is a histological variant of colorectal adenocarcinoma.

UNASSIGNED: Current evidence regarding the association between zinc intake and gastric cancer (GC)-specific survival in patients with intestinal-type GC is lacking. Therefore, this cohort study investigated the association between zinc intake and GC mortality through follow-up on GC death among patients with intestinal-type GC and whether these effects differ according to the source of zinc intake.
UNASSIGNED: A total of 185 patients with intestinal-type GC were enrolled from two hospitals between 2002 and 2006. Their survival or death was prospectively followed up until December 31, 2016, through a review of medical records and telephone surveys.
UNASSIGNED: A total of 178 patients were included and analyzed. The median follow-up period was 7.3 years. In the fully adjusted models, the highest tertile of total zinc intake showed a significantly lower GC mortality than the lowest tertile (hazard ratio, 0.22; 95% confidence interval: 0.08-0.64). In addition, the tertile of total zinc intake showed a dose-response association with GC mortality (p=0.015). Analysis of the source of zinc intake revealed that when zinc intake from staples (rice and noodles), animal, and plant food sources were combined, the results were similar to those of total zinc intake and GC mortality.
UNASSIGNED: Zinc intake through various foods may be effective in reducing GC mortality by achieving balance with other nutrients. Our results suggest that zinc improves the survival of patients with intestinal-type GC in Korea.

Intestinal-type adenocarcinoma is a rare primary vaginal carcinoma. Vaginal adenocarcinomas are most frequently a metastatic lesion, and less commonly, have clear cell histology and occur in young women with diethylstilbestrol (DES) exposure in utero. Due to the limited diagnostic power of immunohistochemistry (IHC) in differentiating primary from metastatic adenocarcinoma of the vagina, clinical and radiological correlation is critical in this scenario. The prognosis of this tumor depends on the patient\'s age, tumor stage, tumor differentiation, lymph node status, and distant metastasis. Several treatment modalities are present depending on the tumor stage. We present a case of primary adenocarcinoma of the vagina and describe the histopathologic features including the immunoprofile of the tumor and discuss the clinicopathologic features, differential diagnosis, diagnostic challenges, and a brief overview of the literature about age, size, site, immunohistochemical staining, and DES exposure.

Intestinal-type adenocarcinoma is a rare primary vaginal carcinoma and considerably more uncommon than metastatic lesions which represent the most frequent malignancy at this anatomic site. Among all malignant tumors, colorectal, breast and female genital tract carcinomas have the tendency to metastasize to the vagina.
As morphologic and immunohistochemical features of intestinal-type adenocarcinoma occurring primarily in the vagina are not specific, clinical and radiologic information is crucial to exclude a metastatic lesion.
Herein we present a rare case of intestinal-type adenocarcinoma from a villous adenoma, presenting as a polypoid mass in the posterior wall of vaginal introitus of 51-year-old menopausal woman. To the best of our knowledge, only 19 cases of intestinal-type adenocarcinoma of the vagina have been reported in the English literature so far. Notably the origin from a previous villous adenoma has been well documented only in a few cases.

We hypothesized that the relative proportion of tumor (PoT) at the luminal surface can predict gastric cancer (GC) patient survival.
We measured the luminal PoT in resection specimens from 231 GC patients with stage II/III disease who had surgery at the Kanagawa Cancer Center, Yokohama, Japan. Tissue microarrays were used to assess the extent of immune cell infiltration by CD45 immunohistochemistry. Results were related to histopathological features and patient overall survival (OS).
PoT was significantly lower in diffuse-type (30%) compared to intestinal-type GC (41%), P = 0.03. Patients with low PoT intestinal-type GC survived significantly longer than patients with high PoT intestinal-type GC (5 years OS: 78% vs 47%, P = 0.0112). Low PoT was an independent favorable prognostic factor in multivariate analysis in intestinal-type GC. Low PoT was correlated with high content of CD45-positive immune cells (P = 0.035). There was no relationship between PoT and survival in diffuse-type GC.
This is the first study to identify a subgroup of patients with stage II/III intestinal-type GC at high risk of recurrence by measuring PoT at the luminal surface. The relationship between PoT and immune cell content provides an initial insight into potential underlying biological mechanisms.

BACKGROUND: While gastric cancer is a common cancer in the world and Iran, its molecular mechanisms are not fully understood as yet. Epigenetic modifications can lead to alteration of gene expression and development of tumorigenesis mechanisms.
METHODS: To clarify the difference in DNA methylation pattern of histological types in gastric carcinoma, CpG islands in the promoters of retinoic acid receptor β gene (RAR-β) was studied using methylation-specific PCR.
RESULTS: In gastric cancer tissues, hypermethylation frequency of RAR-β gene was respectively 61 and 33% for diffuse and intestinal type. In diffuse type, hypermethylation of RAR-β has been significantly associated with invasion (P= 0.007), differentiation (P= 0.033) and location (P= 0.012) of the tumor. However, hypermethylation of RAR-β correlated only with tumor size (P= 0.029) in intestinal type. For adjacent non-tumor samples, hypermethylation of RAR-β was not detected and there was no significant association between age of diagnosis and hypermethylation of RAR-β in both types of gastric cancer.
CONCLUSIONS: These results support previous findings denoting a distinct profile of promoter hypermethylation status in the development of the intestinal and diffuse type of gastric carcinoma and the process of the tumorigenesis in these subtypes of gastric cancer is different from each other.

BACKGROUND: DIXDC1 (Dishevelled-Axin domain containing 1) is a positive regulator of the Wnt pathway. In the field of cancer research, the role of DIXDC1 is unclear. Our previous in vitro study showed that DIXDC1 enhances β-catenin nuclear accumulation in gastric cancer cell lines. The aim of this study was to detect the expression of DIXDC1 in different histological subtypes of gastric carcinoma and to evaluate the correlation between the expression of DIXDC1 and β-catenin localization and clinicopathological parameters, including patients\' survival.
METHODS: Immunohistochemical staining was performed to characterize the expression of DIXDC1 and β-catenin in archived materials from 259 cases of gastric carcinoma. The χ2 test and the Fisher\'s test were used to analyze correlations between DIXDC1 expression, β-catenin localization, and clinicopathological parameters. Univariate analyses were performed using the Kaplan-Meier method, and the survival difference between groups was assessed by the log-rank test. Multivariate analysis was performed using the Cox proportional hazards regression model.
RESULTS: Positive DIXDC1 staining was detected in tumor cells in 123 of 259 (47.5 %) cases. DIXDC1 expression in gastric carcinoma was significantly correlated with the histological intestinal-type (P < 0.001), the depth of tumor invasion (P < 0.001) and the lymph node metastasis (P = 0.006). In the intestinal-type, DIXDC1 was correlated with the nuclear and cytoplasmic β-catenin expression (P = 0.002). Kaplan-Meier analysis indicated that patients with high DIXDC1 expression had poor disease-specific survival (P < 0.001), especially in the intestinal-type. Moreover, multivariate regression analysis showed that positive expression of DIXDC1 was an independent prognostic predictor of intestinal-type gastric carcinoma.
CONCLUSIONS: Our study indicated that DIXDC1 is a significant independent prognostic indicator in intestinal-type gastric carcinoma that plays an important role in carcinogenesis and progression of gastric carcinoma through the Wnt signaling pathway.

OBJECTIVE: To differentiate pancreatobiliary-type from intestinal-type periampullary carcinomas using combined magnetic resonance cholangiopancreatography (MRCP), contrast-enhanced MRI, and diffusion-weighted imaging (DWI).
METHODS: MRI (3.0T) results of 41 patients with pathologically confirmed periampullary carcinoma were retrospectively assessed. Two radiologists, blinded to histologic type of each tumor, evaluated image findings independently. MRCP image features, enhancement pattern, and apparent diffusion coefficient (ADC) values were analyzed. Independent-sample t-test, chi-square, or Fisher\'s exact test were used to determine differential image findings between the pancreatobiliary-type and the intestinal-type group. Cohen\'s κ statistic or interclass correlation coefficient (ICC) were used to evaluate interobserver agreement between two observers. Univariate and multiple logistic regression analysis were performed to identify MRI features with predictive values.
RESULTS: On the basis of hematoxylin-eosin staining, 27 patients were classified as having pancreatobiliary-type carcinomas, and 14 patients the intestinal type. The pancreatobiliary-type carcinomas more commonly showed progressive enhancement than the intestinal type (P = 0.003). The minimum ADC (ADCmin ) value of the pancreatobiliary-type group ([0.95 ± 0.21] × 10(-3) mm(2) /s) was significantly lower than the intestinal-type group ([1.10 ± 0.25] × 10(-3) mm(2) /s) (P = 0.047). For interobserver agreement, the κ values and ICCs for all parameters exceeded 0.8, indicating almost perfect agreement. At multiple logistic regression analysis, the enhancement pattern was the only significant independent predictor (P = 0.011, odds ratio [OR] = 0.105). When the enhancement pattern and ADCmin were used in combination, we could identify 70.4% of pancreatobiliary-type and 78.6% of intestinal-type carcinomas.
CONCLUSIONS: Progressive enhancement and low ADCmin values suggest a pancreatobiliary-type periampullary carcinoma.