Riruke Maruyama

Downregulation of KiSS‐1 expression is responsible for tumor invasion and worse prognosis in gastric carcinoma

KiSS‐1 is a promising candidate tumor‐suppressor gene and may play a key role in the metastatic cascade. The expression profile and the role of KiSS‐1 in cancer progression are largely unknown in most of the cancers, including gastric cancer. In this study, KiSS‐1 expression was evaluated by RNase protection assay and localization was done by in situ hybridization in 40 gastric cancers and their adjacent normal gastric mucosa. For comparison with clinicopathologic characteristics and patient prognosis, all patients were divided into 2 groups having high and low KiSS‐1 expression by using the median as the cutoff value of KiSS‐1 expression as determined by the RNase protection assay. Gastric cancers with low KiSS‐1 had frequent venous invasion, distant metastasis and tumor recurrence. Accordingly, patients with low KiSS‐1‐expressing tumors had a significantly worse overall and disease‐free survival. In multivariate analysis, KiSS‐1 became the strongest independent prognostic factor among the conventional prognosticators for gastric cancer patients. Collectively, these findings suggest that KiSS‐1 may play a crucial role in gastric cancer invasion and could be a useful target for therapeutic intervention.

Crystal Violet Chromoendoscopy with Mucosal Pit Pattern Diagnosis is Useful for Surveillance of Short-Segment Barrett's Esophagus

BACKGROUND:Because of a rapid increase in the incidence of Barretts cancer, the appropriate surveillance method for Barretts esophagus is of interest. Methylene blue chromoendoscopy has been reported to be an effective and inexpensive method to improve biopsy surveillance of Barretts epithelium. However, the usefulness of this method in short-segment Barretts esophagus cases is still controversial.AIMS:This study was undertaken to evaluate the abilities of crystal violet and methylene blue chromoendoscopy to detect potentially dysplastic Barretts epithelium in cases with short-segment columnar-appearing epithelium of the esophago-gastric junction.PATIENTS AND METHODS:Four hundred patients with endoscopically suspected short-segment Barretts esophagus were enrolled and randomly assigned to receive chromoendoscopy with 0.05% crystal violet, 0.1% crystal violet, 0.5% methylene blue, or 1.0% methylene blue. During crystal violet and methylene blue chromoendoscopy, biopsy specimens were obtained from stained and unstained columnar-appearing epithelium of the esophago-gastric junction, and the detection rates of Barretts epithelium were evaluated. The value of pit pattern diagnosis was also evaluated as a possible way to detect dysplastic Barretts epithelium.RESULTS:Chromoendoscopy with 0.05% crystal violet detected histologically confirmed Barretts epithelium with the highest sensitivity (89.2%) and specificity (85.7%). Crystal violet clearly stained both dysplastic and nondysplastic Barretts epithelia and made the surface pit pattern easy to observe without using magnifying endoscopy.CONCLUSIONS:The combination of crystal violet chromoendoscopy and pit pattern diagnosis is considered to be useful for the surveillance of short-segment Barretts esophagus.

Expression of Trefoil Factor Family Members Correlates with Patient Prognosis and Neoangiogenesis

Purpose: Trefoil factor family (TFF) peptides are thought to contribute to epithelial protection and restitution by virtue of their protease-resistant nature and their strong affinity for mucins. However, they are often overexpressed in tumors, where they seem to be negative prognostic factors, possibly contributing to tumor spread, although the precise mechanisms have not been defined. Experimental Design: Tissue sections from 111 patients with curatively resected advanced gastric carcinoma were immunohistochemically stained for TFF2, ITF (TFF3), and CD34. Microvessel density was expressed as number and area of microvessels. Results were correlated with clinicopathological characteristics and patient survival. Results: Forty-nine (44.1%) and 41 (36.9%) tumors were immunohistochemically positive for TFF3 and TFF2, respectively. Among the various clinicopathologic variables, overexpression of TFF3 had a significant correlation with patient age only. In addition, a significantly higher prevalence of positive TFF2 staining was detected in large, diffuse tumors and in tumors with lymph node metastasis. The number of microvessels had a significant correlation with both TFF3 and TFF2 staining, whereas the area of microvessels had a significant correlation only with TFF3 staining. Both TFF3 and TFF2 were independent predictors of a worse disease-free survival. TFF3 had a gender-specific negative survival advantage, with a 91.3% disease-free survival in female patients with TFF3-negative advanced gastric carcinoma. Conclusions: Induction of increased tumor vascularity might be one of the mechanisms by which TFFs confer metastatic phenotype and frequent disease recurrence in gastric carcinomas. Female patients with TFF3-negative advanced gastric carcinoma have comparable survival as that reported for patients with early gastric carcinoma.

Expression of cytoplasmic TFF2 is a marker of tumor metastasis and negative prognostic factor in gastric cancer.

Trefoil factor family 2 (TFF2) is a small peptide constitutively expressed in the gastric mucosa, where it plays a protective role in restitution of gastric mucosa. TFF2 has also been shown to be expressed in some gastric cancers, but its role in tumor metastasis and patient prognosis has not been examined. In this study, we examined TFF2 expression at both the mRNA and protein levels and correlated these results with the clinicopathologic characteristics and prognosis of gastric cancer patients. Among the 144 curatively resected samples, 43 (30%) were positive for TFF2. TFF2 expression was preferentially observed in the infiltrating tumor cells sparing the superficial cells. Significantly increased expression of TFF2 was noted in large tumors of the diffuse type. An increased prevalence of TFF2 expression was also found in tumors with advanced T and N stage and in patients with lymphatic and venous invasion. Accordingly, patients with TFF2-expressing tumors had a significantly worse disease-free survival, and in multivariate analysis, this finding remained significant as an independent prognostic factor. Taken together, our results suggest that TFF2 expression may play a role in gastric cancer invasion and as such could be a useful target for therapeutic intervention.

Prevalence of and risk factors for Barrett's esophagus with intestinal predominant mucin phenotype

Objective. Barretts esophagus with the intestinal predominant mucin phenotype is considered to have a higher malignant potential than that with the gastric predominant mucin phenotype. The purpose of this prospective study was to investigate the prevalence of and risk factors for Barretts esophagus with the intestinal predominant mucin phenotype in patients undergoing endoscopy. Material and methods. A total of 1699 consecutive patients undergoing esophagogastroduodenoscopy were enrolled in the study. A targeted biopsy was performed when endoscopically observed columnar-appearing esophagus was stained with crystal violet. The sample, histologically evidenced as Barretts esophagus, was immunohistochemically evaluated and categorized as of either gastric or intestinal predominant mucin phenotype. All the patients were requested to complete the structured questionnaire indicating their symptoms and food consumption patterns. Prevalence of and risk factors for Barretts esophagus with and without the intestinal predominant mucin phenotype were investigated. Results. Out of 1668 patients, 629 (37.7%) were found to have endoscopic Barretts esophagus. In 333 out of 1668 patients (19.9%), histological studies were diagnostic of Barretts esophagus. One hundred and six of these 333 patients (31.8%) had the intestinal predominant mucin phenotype. Age, male gender and the presence of hiatal hernia were confirmed by multivariate analysis as the independent predictors for the presence of Barretts esophagus with the intestinal predominant mucin phenotype. Conclusions. Barretts esophagus with the intestinal predominant mucin phenotype was immunohistochemically found in 6.4% of all study patients. Older age, male gender and the presence of hiatal hernia were the risk factors for the presence of Barretts esophagus with the intestinal predominant mucin phenotype.

Clinical characteristics of oral adenosquamous carcinoma: report of a case and an analysis of the reported Japanese cases.

We present a case of adenosquamous carcinoma (ASC) which developed in the floor of the mouth of a 72-year-old Japanese man, and review 19 reported ASC cases in Japan from between 1986 and 2001, including the subject case herein. These ASCs occurred at an average age of 63 years, with 74% of the ASCs occurring in the floor of the mouth (8) and the tongue (6); the other sites of occurrence were the palate (3) and mandibular alveolus (2). Chief complaints were painless mass formation (28%), pain and/or sensational abnormality (28%), painful ulcer or swelling (22%), simple ulcer (11%), and miscellaneous others (11%). The clinical presentations of ASC were tumor with ulceration (58%), tumorous mass (26%), and ulcer (16%). Tumor size at first examination varied from bean-size to approximately 65 x 40 mm. In the pretreatment period, 31.3% were known to have cervical lymph node involvement, and descriptions on distant metastasis were not noted in any of the 19 cases. Some of the ASCs were initially diagnosed as other types of lesions, such as squamous cell carcinoma (SCC; 41%), adenocarcinoma (Ad.C; 12%) mucoepidermoid carcinoma (MEC; 6%), and MEC or SCC (6%). After initial treatments, neck and distant metastases were ascertained in 47.1 and 17.6% of the cases, respectively. Generally, a surgical procedure was performed as one of the most critical methods of treatment. The overall 5-year survival rate was 57.0%, with that of patients who underwent active treatment at 60.6%. Our study demonstrates the extent of the varied nature of ASC.

Cerebral myxopapillary ependymoma

A rare case of myxopapillary ependymoma is reported. The tumor occurred in the cerebral hemisphere of an 8-year-old girl and had no relationship to the lateral ventricles. Microscopically, it showed abundant mucin production around papillary or reticular structures. Immunohistochemically, these tumor cells were weakly positive, with glial fibrillary acidic protein demonstrated in part of the tumor and vimentin strongly demonstrated throughout the tumor. The results may indicate the poorly differentiated nature of this tumor. This is the second reported case of intracranial myxopapillary ependymoma.

Reliability of Symptoms and Endoscopic Findings for Diagnosis of Esophageal Eosinophilia in a Japanese Population

Background/Aims: The clinical characteristics of esophageal eosinophilia (EE), which is essential for diagnosis of eosinophilic esophagitis (EoE), have not been fully clarified in a Japanese population. The aim of this study was to analyze the reliability of symptoms and endoscopic findings for diagnosing EE in Japanese individuals. Methods: We prospectively enrolled subjects who complained of esophageal symptoms suggesting EoE and/or those with endoscopic findings of suspected EoE at the outpatient clinics of 12 hospitals. Diagnostic utility was compared between the EE and non-EE groups using logistic regression analysis. Results: A total of 349 patients, including 319 with symptoms and 30 with no symptoms but endoscopic findings suggesting EoE were enrolled. Of those with symptoms, 8 (2.5%) had EE, and 3 were finally diagnosed with EoE. Of those without symptoms but endoscopic findings, 4 had EE. Among 8 symptomatic patients, 7 had abnormal endoscopic findings suspicious of EoE. Although dysphagia was a major symptom in EE, none of the presenting symptoms was useful for diagnosis of EE. Among the endoscopic findings, linear furrow was the most reliable (OR = 41.583). Conclusion: EE is uncommon among patients with esophageal symptoms in Japanese individuals. The most useful endoscopic finding for diagnosis of EE was linear furrow, whereas subjective symptoms were not supportive.

Diffuse laminar endocervical glandular hyperplasia

A case is reported of diffuse laminar endocervical glandular hyperplasia, which is very rare among pseudoneoplastic endocervical glandular lesions. The patient was a 54 year old woman who had been suffering from watery vaginal discharge for about 7 years, and the lesion was found in the cervix of the hysterectomy specimen. Microscopically, the lesion showed a diffuse, Iaminar proliferation of hyperplastic endocervical glands, sharply demarcated from the underlying stroma. The significant nuclear atypia was absent. Inflammatory response was mild. Immunohistochemically, carcinoembryonic antigen was negative. Differential diagnosis from other non‐neoplastic conditions and well differentiated adenocarcinoma is discussed.

Soluble IL-33 receptor sST2 inhibits colorectal cancer malignant growth by modifying the tumour microenvironment

Interleukin-33 (IL-33) was recently shown to be involved in the inflammatory tumour microenvironment and the progression of colorectal cancer (CRC). We report here that the expression level of sST2, a soluble form of the IL-33 receptor (ST2L), is inversely associated with the malignant growth of CRC. sST2 is downregulated in high-metastatic cells compared with low-metastatic human and mouse CRC cells. Knockdown of sST2 in low-metastatic cells enhances tumour growth, metastasis and tumour angiogenesis, whereas its overexpression in high-metastatic cells suppresses these processes. Circulating and intratumourally administered sST2-Fc fusion protein reduce tumour growth, metastatic spread and tumour angiogenesis in mice bearing high-metastatic CRC. Mechanistically, sST2 suppresses IL-33-induced angiogenesis, Th1- and Th2-responses, macrophage infiltration and macrophage M2a polarization. In conclusion, we show that sST2 negatively regulates tumour growth and the metastatic spread of CRC through modification of the tumour microenvironment. Thus, the IL-33/ST2L axis may be a potential therapeutic target in CRC.