Clinical significance of direct fast scarlet staining on the diagnosis of eosinophilic colitis: A comparative study focusing on the eosinophil degranulation in colonic mucosal tissue.

This study aimed to validate the DFS (direct fast scarlet) staining in the diagnosis of EC (eosinophilic colitis). The study included 50 patients with EC and 60 with control colons. Among the 60 control samples, 39 and 21 were collected from the ascending and descending colons, respectively. We compared the median number of eosinophils and frequency of eosinophil degranulation by HE (hematoxylin and eosin) and DFS staining between the EC and control groups. In the right hemi-colon, eosinophil count by HE was useful in distinguishing between EC and control (41.5 vs. 26.0 cells/HPF, p < 0.001), but the ideal cutoff value is 27.5 cells/HPF (high-power field). However, this method is not useful in the left hemi-colon (12.5 vs. 13.0 cells/HPF, p = 0.990). The presence of degranulation by DFS allows us to distinguish between the groups even in the left hemi-colon (58% vs. 5%, p < 0.001). DFS staining also enabled a more accurate determination of degranulation than HE. According to the current standard to diagnose EC (count by HE staining ≥20 cells/HPF), mucosal sampling from left hemi-colon is problematic since the number of eosinophils could not be increased even in EC. Determination of degranulated eosinophils by DFS may potentiate the diagnostic performance even in such conditions.

A case of ovarian serous cystadenofibroma with scattered lesions in pelvic cavity, like malignant disseminations.

Ovarian serous cystadenofibroma is a relatively rare subtype of serous cystadenoma classified as ovarian benign epithelial tumor. We report a rare case of ovarian serous cystadenofibroma with scattered lesions in pelvic cavity, like malignant disseminations. The patient was 22 years old, gravida 0, para 0. In the laparoscopic surgery, numerous hard yellowish-white solid masses of various sizes were present in the bilateral ovaries. Grossly similar masses were scattered in the fimbria of the fallopian tubes, peritoneum, and great omentum. Because the intraoperative rapid histological diagnosis was benign tumor, surgery was completed for only tumor excision. Postoperative histopathological diagnosis is serous cystadenofibroma. Similar pathological findings were noted in the scattered lesions in the peritoneum and great omentum. No malignant or borderline malignant finding was observed. Because of a benign disease, careful treatment taking fertility preservation into consideration is necessary, especially for young patients.

Nuclear staining of claudin-18 is a new immunohistochemical marker for diagnosing intramucosal well-differentiated gastric adenocarcinoma.

Diagnosis of gastric adenocarcinoma using small biopsy samples is occasionally difficult. Various markers have been employed for improving the diagnostic accuracy, but there remains room for improvement. A total of 129 endoscopically biopsied samples were studied, consisting of 104 intramucosal tubular adenocarcinomas, 24 non-cancerous lesions and one cancer sample originally suspected of non-cancer but revised as cancer after immunostaining. We evaluated the association between histopathology and immunohistochemical expression of MUC1, HER2, p53, CEA, E-cadherin, ß-catenin and claudin-18. Regarding ß-catenin and claudin-18, not only membranous expression (ß-catenin(M) and claudin-18(M)) but also nuclear expression (ß-catenin(N) and claudin-18(N)) were analyzed. When subtyped with mucin core protein expression, the gastric-type cancers dominantly expressed claudin-18(M), while claudin-18(N) was significantly encountered in intestinal- and mixed-types. Expression of MUC1 (P = 0.0010), HER2 (P = 0.0173), p53 (P = 0.0002), CEA (P = 0.0019) and claudin-18(N) (P < 0.0001) revealed significant correlation with gastric cancers. Negative correlation of claudin-18(M) (P = 0.0125) was also noted. MUC1 and p53 were negative in non-cancer lesions. The non-cancer group exceptionally expressed HER2 and ß-catenin(N). Membranous expression of E-cadherin was consistent in both groups. Logistic regression analysis showed that MUC1 (P = 0.0086), p53 (P = 0.0031), claudin-18(M) (P = 0.0158) and claudin-18(N) (P = 0.0190) were independently associated with gastric cancers. Nuclear expression of claudin-18 should be the novel diagnostic marker for gastric cancer.

Transduced caudal-type homeobox (CDX) 2/CDX1 can induce growth inhibition on CDX-deficient gastric cancer by rapid intestinal differentiation.

Intestinal metaplasia induced by ectopic expression of caudal-type homeobox (CDX)2 and/or CDX1 (CDX) is frequently observed around gastric cancer (GC). Abnormal expression of CDX is also observed in GC and suggests that inappropriate gastrointestinal differentiation plays essential roles in gastric tumorigenesis, but their roles on tumorigenesis remain unelucidated. Publicly available databases show that GC patients with higher CDX expression have significantly better clinical outcomes. We introduced CDX2 and CDX1 genes separately into GC-originated MKN7 and TMK1 cells deficient in CDX. Marked suppression of cell growth and dramatic morphological change into spindle-shaped flat form were observed along with induction of intestinal marker genes. G0-G1 growth arrest was accompanied by changed expression of cell cycle-related genes but not with apoptosis or senescence. Microarray analyses additionally showed decreased expression of gastric marker genes and increased expression of stemness-associated genes. Hierarchical clustering of 111 GC tissues and 21 non-cancerous gastric tissues by selected 18 signature genes based on our transcriptome analyses clearly categorized the 132 tissues into non-cancer, "CDX signature"-positive GC, and "CDX signature"-negative GC. Gene set enrichment analysis indicated that "CDX signature"-positive GC has lower malignant features. Immunohistochemistry of 89 GC specimens showed that 50.6% were CDX2-deficient, 66.3% were CDX1-deficient, and 44.9% were concomitant CDX2/CDX1-deficient, suggesting that potentially targetable GC cases by induced intestinal differentiation are quite common. In conclusion, exogenous expression of CDX2/CDX1 can lead to efficient growth inhibition of CDX-deficient GC cells. It is based on rapidly induced intestinal differentiation, which may be a future therapeutic strategy.

Expression of Gastric Markers Is Associated with Malignant Potential of Nonampullary Duodenal Adenocarcinoma.

BACKGROUND: Sporadic nonampullary duodenal epithelial tumors (NADETs) are uncommon, and thus their clinicopathological features have not been fully assessed. AIMS: In this study, we have analyzed a series of early sporadic NADETs, focusing on various immunohistological features. METHODS: We conducted a multicenter retrospective analysis of 68 patients with endoscopically resected sporadic NADETs. Associations between immunohistological features and clinicopathological features were statistically analyzed. RESULTS: The 68 patients consisted of 46 men (68%) and 22 women (32%) with a mean age of 60.7 ± 12.2 years (range 37-85 years). The 68 tumors were composed of 39 adenomas (57%) and 29 early-stage adenocarcinomas (43%). Duodenal adenocarcinomas were larger in size than adenomas and had papillary architecture in their pathological diagnosis with statistical significance. Duodenal adenocarcinomas also demonstrated a significantly higher expression of gastric markers (MUC5AC and MUC6) and a higher MIB-1 index. Duodenal adenomas were contrastively apt to express intestinal markers (MUC2, CDX1 and CDX2). Of the 68 cases analyzed, there were only 3 tumors positive for p53 staining, all of which were adenocarcinoma. When 7 submucosal invasive cancers and 21 intramucosal cancers were compared, submucosal invasion was positively associated with expression of MUC5AC. Also, submucosal invasion showed strong association with double-positivity of MUC5AC and MUC6. CONCLUSIONS: Our results indicate that immunohistochemical evaluation is useful for predicting malignant potential of NADETs, especially focusing on the expression of gastrointestinal markers.

Nectin1 expression is frequently decreased in gastric cancers.

Gastric cancer (GC) is rich in many different histological types, but how the histological pattern is defined remains to be proved. The relation between GC histological types and the expression of nectin1, which is one of the cell adhesion molecules that composes adherens junction, has not been reported. According to a publicly available database of 406 GC patients, the median overall survival of Nectin1 high expression patients was 55.4 months and that of low expression patients was 25.6 months (P = 0.0246). Using surgically or endoscopically resected GC samples, nectin1 expression was analyzed by immunohistochemistry. Nectin1 expressed at adherens junction in all the normal epithelial cells. However, nectin1 expressed not at adherens junction but at apical membrane in epithelial cells in intestinal metaplasia. The expression pattern of nectin1 in intestinal type GC resembled to intestinal metaplasia. In order to analyze the difference in nectin1 expression between GC histological types, a total of 116 intestinal type GC and 33 diffuse type GC. The expression of necitin1 in diffuse type GC (3.0%) was remarkably decreased compared to that in intestinal type GC (65.5%) (P < 0.0001). In conclusion, this is the first report showing an association between nectin1 expression and histological subtypes of GC.

Hypertrophic Cardiomyopathy Accompanied by Spinocerebellar Atrophy With a Novel Mutation in Troponin I Gene.

We report the case of a 66 year-old woman with chronic atrial fibrillation, hypertrophic cardiomyopathy (HCM), and spinocerebellar atrophy (SCA). Her mother and first-born son had died of heart disease at the ages of 65 and 16 years, respectively. Four of her 8 siblings had died suddenly of unknown cause or of heart disease, and 2 others of cerebral infarction by the 7th decade. Genetic testing revealed that she had a novel mutation (c. 482C > A, p. Ala161Asp) in the troponin I gene (TNNI3), and no abnormality of the GAA repeat in the frataxin gene. Her older brother with SCA but without HCM was also analyzed, with no abnormality noted in either gene. The Ala161Asp mutation in TNNI3 was implicated in the pathogenesis of her HCM, though an association between HCM and SCA was not revealed.

Application of an enzyme-labeled antigen method for visualizing plasma cells producing antibodies against Strep A, a carbohydrate antigen of Streptococcus pyogenes, in recurrent tonsillitis.

Streptococcus pyogenes is the main causative pathogen of recurrent tonsillitis. Histologically, lesions of recurrent tonsillitis contain numerous plasma cells. Strep A is an antigenic carbohydrate molecule on the cell wall of S. pyogenes. As expected, plasma cells in subjects with recurrent tonsillitis secrete antibodies against Strep A. The enzyme-labeled antigen method is a novel histochemical technique that visualizes specific antibody-producing cells in tissue sections by employing a biotin-labeled antigen as a probe. The purpose of the present study was to visualize plasma cells producing antibodies reactive with Strep A in recurrent tonsillitis. Firstly, the lymph nodes of rats immunized with boiled S. pyogenes were paraformaldehyde-fixed and specific plasma cells localized in frozen sections with biotinylated Strep A. Secondly, an enzyme-labeled antigen method was used on human tonsil surgically removed from 12 patients with recurrent tonsillitis. S. pyogenes genomes were PCR-detected in all 12 specimens. The emm genotypes belonged to emm12 in nine specimens and emm1 in three. Plasma cells producing anti-Strep A antibodies were demonstrated in prefixed frozen sections of rat lymph nodes, 8/12 human specimens from patients with recurrent tonsillitis but not in two control tonsils. In human tonsils, Strep A-reactive plasma cells were observed within the reticular squamous mucosa and just below the mucosa, and the specific antibodies belonged to either IgA or IgG classes. Our technique is effective in visualizing immunocytes producing specific antibodies against the bacterial carbohydrate antigen, and is thus a novel histochemical tool for analyzing immune reactions in infectious disorders.

Multiple microRNAs induced by Cdx1 suppress Cdx2 in human colorectal tumour cells.

The mammalian transcriptional factors, Cdx1 and Cdx2 (Cdx is caudal-type homeobox) are paralogues and critical for the cellular differentiation of intestinal or colorectal epithelia. It has been reported previously that in Cdx1 transgenic or knockout mice, endogenous Cdx2 levels are inversely correlated with Cdx1 levels. Recently, we found that exogenous Cdx1 expression can suppress Cdx2 in a human colorectal tumour cell line, SW480, although the underlying molecular mechanisms were unclear. In the present study, we show that several microRNAs induced by exogenous Cdx1 expression directly bind to the CDX2 mRNA 3'UTR (untranslated region) to destabilize these transcripts, finally leading to their degradation. Using microarray analysis, we found that several miRNAs that were computationally predicted to target CDX2 mRNAs are up-regulated by exogenous Cdx1 expression in SW480 cells. Among these molecules, we identified miR-9, miR-16 and miR-22 as having the potential to suppress Cdx2 through the binding of the 3'UTR to its transcript. Importantly, simultaneous mutations of both the miR-9- and miR-16-binding sites in the CDX2 3'UTR were shown to be sufficient to block Cdx2 suppression. The results of the present study suggest a unique feature of miRNAs in which they contribute to homoeostasis by limiting the levels of transcription factors belonging to the same gene family.

Rebamipide induces dendritic cell recruitment to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-exposed rat gastric mucosa based on IL-1ß upregulation.

Rebamipide is usually used for mucosal protection, healing of gastric ulcers, treatment of gastritis, etc., but its effects on gastric malignancy have not been elucidated. Using Lewis and Buffalo rat strains treated with peroral administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), we evaluated the effect of rebamipide on the induction of tumor-suppressive dendritic cells, which are known to be heterogeneous antigen-presenting cells of bone marrow origin and are critical for the initiation of primary T-cell responses. Using CD68 as a marker for dendritic cells, the stomach pyloric mucosae of Lewis and Buffalo rats were immunohistochemically analyzed in the presence or absence of rebamipide and MNNG. After a 14-day treatment of rebamipide alone, no significant change in number of CD68-expressing cells was detected in either rat strain. However, after concurrent exposure to MNNG for 14 days, treatment with rebamipide slightly increased CD68-positive cells in the Lewis strain, and significantly increased them in the Buffalo strain. Analysis of two chemotactic factors of dendritic cells, IL-1ß and TNF-α, in the gastric cancer cells showed that expression of IL-1ß, but not TNF-α, was induced by rebamipide in a dose-dependent manner. A luciferase promoter assay using gastric SH-10-TC cells demonstrated that an element mediating rebamipide action exists in the IL-1ß gene promoter region. In conclusion, rebamipide has potential tumor-suppressive effects on gastric tumorigenesis via the recruitment of dendritic cells, based on the upregulation of the IL-1ß gene in gastric epithelial cells.

Colonic Lymphoid Follicle Hyperplasia after Gastrectomy in Rats.

Nodular lymphoid hyperplasia (NLH) of the human colon has been associated with multiple diseases and symptoms. Causes include food allergies, infections, inflammatory bowel disease, and immunodeficiency, and gastrectomy is not usually considered to be the etiology. Nine rats two weeks after total gastrectomy and 12 control rats were sacrificed and submitted for histological examination. In the gastrectomy group, we found lymphoid hyperplasia throughout the entire colon mucosa. The cross-sectional area of lymphoid follicles was increased to be five-fold larger than that in the rats in the control group (sham surgery). Lymphoid follicles were classified into primary and secondary follicles according to the presence/absence of germinal centers; the gastrectomy group had a significantly larger number of secondary follicles. When T cell and B cell classification of lymphocytes was performed, there was no difference between gastrectomy and control groups at T:B = 40:60. When the lymphoid follicles were classified, the proportion of T lymphocytes increased in the secondary follicle (T:B = 40:60) compared with in the primary follicle (T:B = 20:80). Gastrectomy significantly activated lymphocytic intestinal immunity by altering the intestinal environment, causing colonic NLH. Gastrectomy in rats is a good animal model for the study of NLH in colorectal diseases.

Enzyme-labeled Antigen Method: Factors Influencing the Deterioration of Antigen-binding Activity of Specific Antibodies during Formalin Fixation and Paraffin Embedding.

The enzyme-labeled antigen method is an immunohistochemical technique detecting plasma cells producing specific antibodies in tissue sections. The probe is an antigen labeled with an enzyme or biotin. This immunohistochemical technique is appliable to frozen sections of paraformaldehyde (PFA)-fixed tissues, but it has been difficult to apply it to formalin-fixed, paraffin-embedded (FFPE) sections. In the current study, factors inactivating the antibody reactivity during the process of preparing FFPE sections were investigated. Lymph nodes of rats immunized with horseradish peroxidase (HRP) or a mixture of keyhole limpet hemocyanin/ovalbumin/bovine serum albumin were employed as experimental models. Plasma cells producing specific antibodies, visualized with HRP (as an antigen with enzymatic activity) or biotinylated proteins in 4% PFA-fixed frozen sections, significantly decreased in unbuffered 10% formalin-fixed frozen sections. The positive cells were further decreased by paraffin embedding following formalin fixation. In paraffin-embedded sections fixed in precipitating fixatives such as ethanol and acetone and those prepared with the AMeX method, the antigen-binding reactivity of antibodies was preserved. Fixation in periodate-lysine-paraformaldehyde and Zamboni solution also kept the antigen-binding reactivity in paraffin to some extent. In conclusion, formalin fixation and paraffin embedding were major causes inactivating antibodies. Precipitating fixatives could retain the antigen-binding reactivity of antibodies in paraffin-embedded sections.

Heterotopic ossification in primary rectal cancer with squamous cell carcinoma-like differentiation.

Objectives: Heterotopic ossification (HO), which occurs when bone tissue forms outside the skeleton, is extremely rare in rectal cancer. Adenocarcinoma is the histological type of all reported primary colorectal cancers with HO. However, in the present case, we observed areas of adenocarcinoma with squamous cell carcinoma-like differentiation. Here we conducted histopathological and immunohistochemical analyses to identify the mechanisms of HO development, to differentiate between adenocarcinoma and squamous cell carcinoma-like phenotypes, and to understand the associated prognostic implications. Case report: A 62-year-old woman was admitted to our hospital with symptoms of intermittent hematochezia without abdominal pain. Colonoscopy revealed stenosis with a protuberant mass in the rectum. Abdominopelvic contrast-enhanced computed tomography showed irregular wall thickness of the rectum, multiple lymph node metastases, and liver metastases. The rectal tumor exhibited calcified deposits with marked hyperintensity. We then performed Hartmann's operation and D3 lymph node resection. The biopsy specimen revealed tubular and solid adenocarcinoma nests and squamous carcinoma-like components over a necrotic extent without secreted mucin. She received chemotherapy (mFOLFOX6 with bevacizumab) as the first option and is alive 5 months after surgery. Conclusion: To the best of our knowledge, this is the first case of heterotopic ossification in a primary rectal cancer with squamous cell carcinoma-like differentiation that was surgically resected. This case suggests that BMP-2 transformed fibroblasts and pluripotent stem cells into osteocytes. We conclude that the squamous cell carcinoma-like lesion was squamous metaplasia of adenocarcinoma.

Molecular epidemiology of a hepatitis C virus outbreak in a leprosy sanatorium in Japan.

The hepatitis C virus (HCV) outbreak that occurred between 1940 and 1999 in a closed leprosy sanatorium located on a small island in Japan was analyzed. The analysis of 318 nucleotides in the NS5B region of HCV allowed us to establish the existence of at least three different HCV strains in this sanatorium.

A Prunus mume extract stimulated the proliferation and differentiation of osteoblastic MC3T3-E1 cells.

Osteoporosis is a serious disease caused by decreased bone mass. There is constant matrix remodeling in bones, by which bone formation is performed by osteoblastic cells, whereas bone resorption is accomplished by osteoclast cells. We investigated the effect of a Japanese apricot (Prunus mume SIBE. et ZUCC.) extract on the proliferation and osteoblastic differentiation in pre-osteoblastic MC3T3-E1 cells. An alkaline phosphatase (ALP) activity assay, cell proliferation assay, alizarin red staining and expression analysis of osteoblastic genes were carried out to assess the proliferation and osteoblastic differentiation. The water-soluble fraction of Prunus mume (PWF) increased the ALP activity, cell proliferation and mineralization. The gene expression of osteopontin and bone morphogenetic protein-2, which are markers in the early period of osteoblastic differentiation, were significantly enhanced by the PWF treatment. PWF therefore stimulated the proliferation and osteoblastic differentiation of cells and may have potential to prevent osteoporosis.

Hepatitis C virus infection in a Japanese leprosy sanatorium for the past 67 years.

Oku-Komyo-En is one of the national leprosy sanatoria, located on a small island in Setouchi city, Okayama prefecture of Japan since 1938. Since autopsies were carried out routinely on almost all patients who had died in the sanatorium up to 1980, approximately 1,000 formalin-fixed autopsy tissue samples were available for analysis. When these samples were reviewed, the pathological data indicated a sharp rise in the death rate caused by cirrhosis of the liver and hepatocellular carcinoma (HCC) since 1960 and 1970, respectively. Hepatitis C virus (HCV) infection is a common cause of HCC in Japan. The presence of HCV RNA was demonstrated in paraffin sections prepared from the autopsied liver tissue fixed in formalin for a prolonged period of time, by employing nested RT-PCR using type-specific primers. The data showed that HCV RNA was detectable in samples of the liver archived as early as 1940, representing the liver tissues kept in formalin for up to 67 years. HCV genotypes 1b and 2a were found by RT-PCR at 85.7% and 14.3%, respectively, in patients with leprosy.

Cdx2 and the Brm-type SWI/SNF complex cooperatively regulate villin expression in gastrointestinal cells.

In our recent study showing a correlation between Brm-deficiency and undifferentiated status of gastric cancer, we found that the Brm-type SWI/SNF complex is required for villin expression. To elucidate intestinal villin regulation more precisely, we here analyzed structure and function of the promoter of human villin. About 1.1 kb upstream of the determined major transcription start site, we identified a highly conserved region (HCR-Cdx) among mammals, which contains two binding sites for Cdx. Expression analyses of 30 human gastrointestinal cell lines suggested that villin is regulated by Cdx2. Introduction of Cdx family genes into colorectal SW480 cells revealed that villin is strongly induced strongly by Cdx2, moderately by Cdx1, and marginally by Cdx4. Knockdown of Cdx2 in SW480 cells caused a clear downregulation of villin, and reporter assays showed that HCR-Cdx is crucial for Cdx2-dependent and Brm-dependent villin expression. Immunohistochemical analyses of gastric intestinal metaplasia and cancer revealed that villin and Cdx2 expression are tightly coupled. GST pull-down assays demonstrated a direct interaction between Cdx2 and several SWI/SNF subunits. Chromatin immunoprecipitation analyses showed the recruitment of Cdx2 and Brm around HCR-Cdx. From these results, we concluded that Cdx2 regulates intestinal villin expression through recruiting Brm-type SWI/SNF complex to the villin promoter.

Enzyme-labeled antigen method: histochemical detection of antigen-specific antibody-producing cells in tissue sections of rats immunized with horseradish peroxidase, ovalbumin, or keyhole limpet hemocyanin.

The enzyme-labeled antigen method is a histochemical technique that visualizes antigen-specific antibody-producing cells in tissue sections, originally documented in 1968. In this study, we attempted to reemerge this hidden but potentially useful method in rat models immunized with horseradish peroxidase (HRP), ovalbumin (OA), or keyhole limpet hemocyanin (KLH). After repeated immunization in footpads, popliteal, groin, and axillary lymph nodes and spleen were sampled. Paraformaldehyde-prefixed frozen sections were incubated with HRP, biotinylated OA, or biotinylated KLH. Proteinase K pretreatment and the secondary use of HPR-labeled streptavidin were applied in the latter two situations. Plasma cells producing antigen-specific antibodies were visualized. Proportions of antigen-specific antibody-producing cells in total plasma cells shown with the immunoperoxidase method for rat immunoglobulins were evaluated. The percentage of antigen-specific plasma cells reached approximately 50% of total plasma cells in the regional lymph nodes. The specificity was confirmed by (a) negativity in non-immune rat tissue, (b) negativity with indifferent antigen probes, and (c) abolishment of the reactivity with the corresponding rat serum. In buffered formalin-fixed, paraffin-embedded tissues, fewer plasma cells were labeled for HRP and KLH antibody reactivity after strong proteolysis and prolonged incubation. Expectedly, this method allows us to observe antigen-specific antibody-producing cells under varied pathological conditions.

Identification of marker genes and pathways specific to precancerous duodenal adenomas and early stage adenocarcinomas.

BACKGROUND: The mechanism behind the pathogenesis and carcinogenesis of these neoplasms is not fully understood. The objective of this study was to identify genetic markers and pathways specific to precancerous duodenal adenomas and early stage adenocarcinomas through gene expression analysis. METHODS: Gene expression profiling was performed in 4 pairs of duodenal adenoma/adenocarcinomas and corresponding matched normal tissue. Genes with consistent expression differences were identified and confirmed in 7 independent pairs. Gene set enrichment analysis (GSEA) was performed to characterize gene expression profiles of duodenal adenoma/adenocarcinomas, together with immunohistochemical staining of candidate oncogenic genes. RESULTS: 626 probes consistently demonstrated over a twofold expression difference between tumor-normal pairs. Reverse transcriptase polymerase chain reaction of genes with the most prominent difference in expression between tumors and normal mucosa (KLK7, KLK6, CEMIP, MMP7, KRT17, LGR5, G6PC, S100G, APOA1) validated the results of gene expression analysis. GSEA demonstrated a strong association between duodenal adenoma/adenocarcinomas with colorectal adenomas (p < 10-5) and gene expression patterns seen after APC gene knockout (p < 10-5), suggesting that the Wnt/ß-catenin pathway plays a crucial role in the carcinogenesis of these neoplasms. Immunohistochemical staining of an independent group of duodenal adenomas confirmed over-accumulation of ß-catenin in 80.0% (16/20). CONCLUSIONS: Precancerous duodenal adenomas and early stage adenocarcinomas demonstrate gene expression characteristics with a strong resemblance to colorectal adenomas. The results of this study strongly suggest that upregulation of the Wnt/ß-catenin pathway is the major factor involved in the initial stages of the carcinogenesis of duodenal adenocarcinomas.

Acquisition of resistance to androgen deprivation therapy in salivary duct carcinoma: A case report.

Salivary duct carcinoma is a relatively rare salivary cancer, and most cases are androgen receptor -positive. Salivary duct carcinoma growth is suggested to be androgen dependent, which can reportedly be controlled by androgen deprivation therapy. However, the effectiveness and underlying molecular mechanisms of androgen deprivation therapy for salivary duct carcinoma remain unknown. We report a salivary duct carcinoma case (65-year-old man) arising from the parotid gland with metastasis to the neck lymph nodes and lungs. Androgen deprivation therapy was performed according to the same protocol for prostate cancer treatment. Expression levels of androgen receptor and FOXA1 (forkhead box A1) were immunohistochemically analyzed before and after androgen deprivation therapy. Although the tumor volume was partially diminished during the first 3 months, acquired resistance to androgen deprivation therapy occurred. FOXA1 was not detected in parotid gland after androgen deprivation therapy, whereas androgen receptor expression was positive. FOXA1 expression might be related to acquired androgen deprivation therapy resistance in salivary duct carcinoma.