Hemorrhagic Gastric Metastasis from Hepatocellular Carcinoma Successfully Treated Using Coil Embolization of the Left Gastric Artery.

A 62-year-old man initially underwent transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma (HCC). One year after the initial treatment, he developed anemia. Upper gastrointestinal endoscopy revealed irregularly elevated tumors in the lower anterior gastric body, which were diagnosed to be metastasis from HCC. Left gastric artery coil embolization was performed to prevent sustained bleeding, and his anemia partially improved. In addition to direct invasion, hematogenous metastasis to the stomach from HCC is possible and therefore should be considered during treatment. Transcatheter arterial embolization for gastric metastasis is an effective treatment method which achieves a good degree of hemostasis in patients without any surgical indications.

[Unresectable combined hepatocellular-cholangiocellular carcinoma treated with transcatheter arterial chemoembolization and gemcitabine: a case study].

A 76-year-old female was referred to our hospital because of liver dysfunction. Abdominal contrasted computed tomography (CT) revealed a tumor of 7.5cm in the hepatic hilar area. Based on the biopsy, the tumor was diagnosed by as combined hepatocellular-cholangiocellular carcinoma (with stem-cell features). The tumor was considered unresectable;hence, the patient underwent transcatheter arterial chemoembolization (TACE). However, a CT scan revealed the treatment to be ineffective. Subsequently, systemic gemcitabine (GEM) chemotherapy was administered and tumor shrinkage was observed with reperfusion of the umbilical portion of the left portal vein. The patient's condition is currently stable 17 months after diagnosis, with no tumor regrowth on account of repeated TACE and GEM therapy. The present case of unresectable combined hepatocellular-cholangiocellular carcinoma was successfully treated using TACE and systemic GEM chemotherapy.

[A Resected Case of Long-Term Survival of Pancreatic Cancer with Simultaneous Multiple Lung Metastasis with Systemic Chemotherapy].

The patient was a 78-year-old man with resection of distal pancreatectomy for pancreatic cancer with simultaneous multiple lung metastasis. They were papillary and tubular adenocarcinoma, Pt, TS3, infiltrative type, ly0, v0, pT3, CH0, DU0, S1, RP1, PV0, A1(Asp), PL0, OO0 and pN0, M1(PUL), pStage IV. He was received gemcitabine after the surgery. S-1 was added because of lung metastasis progression. Chemotherapy was continued for about 10 years from resection, and intra-abdominal recurrence was not observed and good performance status was maintained. 5-year survival rate of pancreatic cancer is as low as about 6.5%in Stage IV. There are cases where lung resection to isolated lung metastasis are performed after resection of pancreas and long-term-survival are obtained. A resected case of long-term-survival of pancreatic cancer with simultaneous multiple lung metastasis is rare, so we will report with a few literature considerations.

Re-evaluation of Phenotypic Expression in Differentiated-type Early Adenocarcinoma of the Stomach.

A total of 313 cases of differentiated-type early gastric adenocarcinomas, including 113 cases of small-sized carcinoma (5< × ≤10 mm) and 121 cases of microcarcinoma (0< × ≤5 mm), were examined immunohistochemically to clarify the phenotypic expressions. They were classified into four categories (gastric phenotype (G-type), intestinal phenotype, gastrointestinal phenotype, and null phenotype) by a two-step process: the phenotype based on an immunoprofile of mucin core proteins (MUCs) with CDX2 (w/.CDX2-assessment); and the phenotype of MUCs only (w/o.CDX2-assessment). CDX2 expression was observed in 89.1% (279/313); it was highly expressed in 87.6% (106/121) of microcarcinomas. MUC2 expression increased as tumor size increased (P < 0.05). Compared with w/o.CDX2-assessment, w/.CDX2-assessment showed significantly fewer G-type carcinomas (P < 0.05). Each phenotype marker was less expressed in the submucosal part than in the mucosal part. In conclusion, CDX2 was a sensitive marker for assessing intestinal phenotype. A large portion of the early differentiated-type adenocarcinomas expressed CDX2 from the very early stage of carcinogenesis, and the proportion of G-type was unexpectedly low. Lower expression of each phenotype marker was considered the cause of phenotype alteration during submucosal invasion.

[Three Cases of Long-Term Survival in Colon Cancer with Postoperative Peritoneal Recurrence].

Case 1 is a 57-year-old man with pelvic recurrence 1 year 8 months after surgery for ascending colon cancer.We performed a Hartmann's operation.He has been relapse-free for 11 years.Case 2 is a 67-year-old man with intraperitoneal small intestinal relapse 4 years after surgery for cecum cancer.We performed resection.He has brain metastases recurrence in 2 years 6 months after surgery, died after 2 years 9 months.Case 3 is a 53-year-old man with recurrence in the bladder rectal fossa 5 years after sigmoidectomy.We performed resection.He has been relapse-free survival at 1 year 2 months.

Assessment of gastric phenotypes using magnifying narrow-band imaging for differentiation of gastric carcinomas from adenomas.

Background. Conventional white-light endoscopy and forceps biopsy are insufficient for definitive diagnosis of gastric adenoma. Immunohistochemical studies have reported an obvious phenotypic difference between adenomas and carcinomas. We investigated the utility of narrow-band imaging with magnifying endoscopy (NBI-ME) for mucin phenotypic assessment to differentiate carcinomas from adenomas. Methods. NBI-ME findings were classified into A, B, and AB types, which revealed papillary, tubular pits and groove microstructures, respectively. To investigate A-B classifications retrospectively, 137 patients (155 lesions) that were diagnosed pretherapeutically with adenoma or borderline lesions by biopsy were enrolled. The mucin phenotype was analyzed immunohistochemically in the first 60 lesions. Results. After endoscopic submucosal dissection, A type and AB type lesions were determined histologically as carcinoma (81/82, 99%). B type lesions were adenoma (29/73, 40%) and carcinoma (44/73, 60%). A or AB type correlated to histological carcinomas (sensitivity 65%, specificity 97%, and accuracy 71%). Mucin phenotypes were gastric or gastrointestinal in A type and AB type carcinomas (31/37, 84%) and intestinal in B type adenomas and carcinomas (21/23, 91%). Conclusions. NBI-ME has the advantage of the assessment of mucin phenotypes in gastric carcinomas and adenomas. The proposed A-B classification is useful, especially for differentiation of gastric or gastrointestinal carcinomas from adenomas.

Mucin phenotype expression of gastric neuroendocrine neoplasms: analysis of histopathology and carcinogenesis.

BACKGROUND: Gastric neuroendocrine neoplasia has been classified as neuroendocrine tumor (NET), a less-malignant type, and neuroendocrine carcinoma (NEC), a more-malignant type. We investigated phenotypic expression profiles to clarify the differences between NET and NEC in terms of histopathology and carcinogenesis. METHODS: We assayed 86 cases of gastric neuroendocrine neoplasms (NET G1, n = 25; NET G2, n = 9; NEC, n = 52), using six exocrine markers (MUC5AC, human gastric mucin, MUC6, M-GGMC-1, MUC2, and CDX2). RESULTS: NEC frequently coexisted with adenocarcinomatous components (75 %; 39 of 52) and the majority (71.8 %; 28 of 39) showed intraglandular endocrine cell hyperplasia, although no cases of NET showed adenocarcinomatous components. Mucin phenotype significantly differed between NET and NEC; none of NET cases expressed any exocrine markers other than CDX2, although the majority of NEC (86.5 %; 45 of 52) expressed at least one or more exocrine markers with various positive rates for each marker (range, 8.2-74.0 %). Each NEC component showed only the phenotype expressed in the adenocarcinomatous component in the same tumor. Furthermore, double immunohistochemistry revealed dual expression of CDX2 and chromogranin A in half the NEC cases (23 of 46). CONCLUSIONS: These data suggest that gastric NETs (G1 and G2) and NECs have different processes of carcinogenesis, and gastric NECs may be generated from preceding adenocarcinomas.

Magnifying narrow-band imaging of surface maturation in early differentiated-type gastric cancers after Helicobacter pylori eradication.

BACKGROUND: Even after successful Helicobacter pylori eradication, primary or metachronous gastric cancers are sometimes discovered. The endoscopic features of these cancers may be modified by controlling inflammation. Characteristic findings for such lesions in terms of narrow-band imaging with magnifying endoscopy (NBI-ME) and histopathology need to be clarified to allow accurate diagnosis. METHODS: Distinctive NBI-ME characteristics were examined retrospectively in intramucosal or minimally submucosal and differentiated-type adenocarcinomas from a successful eradication group (42 patients, 50 lesions) and a non-eradicated control group (44 patients, 50 lesions) matched in age and sex. A "gastritis-like" appearance under NBI-ME was characterized by uniform papillae and/or tubular pits with a whitish border, regular or faint microvessels and unclear demarcation, resembling the adjacent noncancerous mucosa. Histological differentiation at the luminal surface of the cancer was evaluated according to Ki-67 immunoreactivity restricted at the middle or lower portion of the tubules. NBI-ME alteration was prospectively confirmed in 29 patients (30 lesions) after eradication therapy. RESULTS: The frequency of a "gastritis-like" appearance was 44% (22/50) for the eradication group, which was significantly higher than the 4% (2/50) for the control group (p < 0.001). In the eradication group, the "gastritis-like" appearance was significantly correlated with histological surface differentiation (p < 0.001). In the prospective study, NBI-ME showed changes to heterogeneous papillary microstructures in 43% (10/23) of the lesions after successful eradication at short-term follow-up. CONCLUSIONS: Identification of surface maturation under NBI-ME offers a promising approach for accurate diagnosis of early gastric cancers after successful eradication.

Re-evaluation of phenotypic expression in undifferentiated-type early gastric adenocarcinomas using mucin core protein and CDX2.

BACKGROUND: Undifferentiated-type early gastric adenocarcinomas are generally classified into two groups: pure undifferentiated-type adenocarcinomas, which naturally develop as undifferentiated-type without a glandular component; and mixed differentiated/undifferentiated-type adenocarcinomas, which are associated with some vestigial glandular component and presumably develop from differentiated-type adenocarcinoma. The differences in phenotypic expression between these two groups were examined using mucin core protein and CDX2. METHODS: A total of 210 lesions of undifferentiated-type early gastric adenocarcinoma less than 25 mm in diameter were classified into four categories (gastric type, gastrointestinal type, intestinal type, and null type) based on their MUC5AC, MUC6, MUC2, and CDX2 immunoprofiles. RESULTS: Gastric type was significantly (p < 0.01) decreased and gastrointestinal type was significantly (p < 0.01) increased both in pure undifferentiated-type adenocarcinomas and in mixed differentiated/undifferentiated-type adenocarcinomas when CDX2 was applied to mucin core protein. In the pure undifferentiated-type adenocarcinomas, gastric type decreased and gastrointestinal type increased as tumor size increased (p < 0.05). In contrast, in the mixed differentiated/undifferentiated-type adenocarcinomas, gastrointestinal type was most common even in small-sized (≤10 mm) carcinomas and was generally stable regardless of tumor size. In submucosal carcinomas, gastrointestinal type decreased and gastric type and intestinal type increased during carcinoma invasion from the intramucosal to submucosal parts (p < 0.05). The positivity rates for all phenotypic markers, especially gastric markers, tended to decrease during submucosal invasion. CONCLUSIONS: CDX2 is a sensitive marker for assessing intestinal phenotypic expression, and it is likely that there are two different pathways of tumor progression in undifferentiated-type adenocarcinoma of the stomach, according to phenotypic expression.

Alpha-methylacyl-coenzyme A racemase expression in neuroendocrine neoplasms of the stomach.

The enzyme alpha-methylacyl-coenzyme A racemase plays an important role in the beta-oxidation of branched-chain fatty acid and its derivatives. It has been used to detect prostatic adenocarcinoma and high-grade intraepithelial neoplasia, and recently also as a marker for other neoplasms, including those of the genitourinary system, breast, upper and lower gastrointestinal tract and their precursor lesions. We assessed expression of alpha-methylacyl-coenzyme A racemase by immunohistochemistry in neuroendocrine tumours of the stomach to determine differences in the incidence and pattern of expression among different types of gastric neuroendocrine tumours. While none of the grade 1 neuroendocrine tumours were immunoreactive, 67 % of grade 2 neuroendocrine tumours and 90 % of neuroendocrine carcinomas were positive for alpha-methylacyl-coenzyme A racemase. Furthermore, an adenocarcinoma component was found in 72.5 % (37 of 51) of neuroendocrine carcinomas, whereas none of the grade 1 and 2 neuroendocrine tumours contained an adenocarcinoma component. In 83 % of neuroendocrine carcinomas, the adenocarcinoma component was positive for alpha-methylacyl-coenzyme A racemase, and both adenocarcinoma and neuroendocrine carcinoma components stained positively in 78 % of these cases. Our results indicate that alpha-methylacyl-coenzyme A racemase is a useful marker for distinguishing between grade 1 (negative) and grade 2 neuroendocrine tumours, and neuroendocrine carcinoma of the stomach (frequently positive). Different patterns of alpha-methylacyl-coenzyme A racemase expression between gastric neuroendocrine tumours and neuroendocrine carcinoma suggest that these might develop via different tumourigenic pathways.

Relationship between alpha-methylacyl-coenzyme A racemase expression and mucin phenotype in gastric cancer.

Alpha-methylacyl-coenzyme A racemase controls ß-oxidation of branched-chain fatty acid and their derivatives. Many investigators have described alpha-methylacyl-coenzyme A racemase expression in various neoplasias and their precursor lesions. Although there have been a few reports regarding alpha-methylacyl-coenzyme A racemase expression in gastric neoplasia, these reports did not discuss the relationship between alpha-methylacyl-coenzyme A racemase expression and mucin phenotype. This study analyzed alpha-methylacyl-coenzyme A racemase expression of gastric carcinomas with regard to mucin phenotype. Alpha-methylacyl-coenzyme A racemase expression was evaluated in 85 cases of gastric biopsies including gastric epithelial neoplasia and nonneoplasia and in 108 cases of surgically resected early gastric cancer. In biopsy cases, alpha-methylacyl-coenzyme A racemase was more highly expressed in neoplasia (69.7%, 23/33) than in nonneoplasia (0%, 0/42) (P = .001). Alpha-methylacyl-coenzyme A racemase was overexpressed in 20.0% (2/10) of cases that were indefinite for neoplasia, and the 2 positive cases were ultimately diagnosed as adenocarcinoma. In resected cases of early gastric adenocarcinoma, alpha-methylacyl-coenzyme A racemase expression significantly correlated with mucin phenotype (P = .003), but not with tumor progression, histologic classification, or clinicopathologic features. Alpha-methylacyl-coenzyme A racemase expression was significantly higher in intestinal-phenotype carcinoma (90.2%, 37/40) than in gastric-phenotype carcinoma (56.3%, 18/31) (P = .006) and also correlated with an increase in CDX2 expression (P = .018) and a decrease in MUC5AC expression (P = .048). This tendency was observed in all histologic types. Our results indicate that alpha-methylacyl-coenzyme A racemase is a useful marker for distinguishing gastric neoplasia from nonneoplasia even at an early stage. Alpha-methylacyl-coenzyme A racemase expression is associated with mucin phenotypes of gastric neoplasia, particularly with the expression of CDX2 and MUC5AC.

Secondary resistance to imatinib mesylate 70 months after initiation of therapy in a patient with a metastatic gastric gastrointestinal stromal tumor.

It is unknown how long the risk of developing secondary resistance to imatinib persists in patients with gastrointestinal stromal tumors (GISTs). Here we report a case of a patient with a metastatic gastric GIST who developed secondary resistance to imatinib 70 months after initiation of imatinib therapy. A 62-year-old woman with a gastric GIST underwent total gastrectomy with pancreaticosplenectomy. Immunohistochemistry revealed a KIT-positive GIST. The mitotic index of the tumor was 13/50 high-power fields, indicating a high-risk malignancy. After surgery, the patient developed a solitary liver metastasis and underwent right hepatic lobectomy. Four months later, a metastatic tumor was found at the left adrenal gland, and imatinib therapy was initiated in December 2004. Imatinib therapy led to marked tumor shrinkage and complete clinical remission in the patient. However, in October 2010, computed tomography scans revealed a peritoneal metastasis in the ileocecal area. The tumor progression was clinically determined to be due to the development of secondary resistance to imatinib, and the patient's treatment was switched to sunitinib. This case illustrates secondary resistance to imatinib can develop even after a sustained and marked treatment response. Long-term therapy and close monitoring are recommended for the management of patients with metastatic GISTs.

A case of a choledochal cyst associated with a lymphatic infiltration of a hyperplastic gallbladder epithelium.

A 4-year-old girl with a congenital choledochal cyst (Todani IV-A, Komi type A) underwent a resection of the dilated common bile duct and gallbladder. Histologic studies of the gallbladder showed a general hyperplastic change associated with cribriform proliferation at the gland base of the gallbladder. In this region, clusters of cribriform glands were found within the lymphatic vessels, compatible with lymphatic infiltration of tumor cells. However, careful histologic studies did not reveal any apparent neoplastic changes in the gallbladder and common bile duct, so a final diagnosis of epithelial atypism with reactive hypertrophy was made. The displacements observed in the lymphatics are just an incidental finding in a proliferative process of the hyperplastic gallbladder epithelium. In the follow-up observation for 3 years, the patient is doing well without evidence of tumor recurrence. These results suggest that a mere lymphatic infiltration of hyperplastic gallbladder epithelium should not be directly considered as evidence of carcinogenesis.

Genetic changes of p53, K-ras, and microsatellite instability in gallbladder carcinoma in high-incidence areas of Japan and Hungary.

AIM: To disclose geographic differences in genetic changes involved in gallbladder carcinogenesis between two distinct high-incidence areas of Japan and Hungary. METHODS: We examined 42 cases of gallbladder carcinoma: 22 Japanese and 20 Hungarian cases. p53 mutations at exons 5 to 8 and K-ras mutations at codon 12 were tested by direct sequencing. Microsatellite instability was determined from fluorescent dye-labeled PCR amplifications of five-microsatellite markers (BAT-25, BAT-26, D2S123, D5S346, and D17S250). RESULTS: Mutations of p53 were detected in 11 of 22 Japanese cases and 6 of 18 Hungarian cases (11/22 vs 6/18, P = 0.348). Transition at CpG sites was found in none of 11 Japanese cases and 2 of 6 Hungarian cases; the difference was marginally significant (0/11 vs 2/6, P = 0.110). K-ras mutations were detected in only one of the Hungarian cases. Eight of 19 (42.1%) Japanese cases were MSI-high (presence of novel peaks in more than one of the five loci analyzed), whereas only 1 of 15 (6.7%) Hungarian cases was MSI-high (P = 0.047). CONCLUSION: It appears that the p53 mutations and MSI differ in patients with gallbladder carcinoma between two distinct high-incidence areas. Geographic variation might exist in the process of gallbladder carcinogenesis.

Establishment and characterization of monoclonal and polyclonal antibodies against human intestinal fatty acid-binding protein (I-FABP) using synthetic regional peptides and recombinant I-FABP.

We have succeeded in raising highly specific anti-human intestinal fatty acid-binding protein (I-FABP) monoclonal antibodies by immunizing animals with three synthetic regional peptides, i.e., the amino terminal (RP-1: N-acetylated 1-19-cysteine), middle portion (RP-2: cysteinyl-91-107) and carboxylic terminal (RP-3: cysteinyl-121-131) regions of human I-FABP, and the whole I-FABP molecule as antigens. We also raised a polyclonal antibody by immunizing with a recombinant (r) I-FABP. To ascertain the specificity of these antibodies for human I-FABP, the immunological reactivity of each was examined by a binding assay using rI-FABP, partially purified native I-FABP and related proteins such as liver-type (L)-FABP, heart-type (H)-FABP, as well as the regional peptides as reactants, and by Western blot analysis. In addition, the expression and distribution of I-FABP in the human gastrointestinal tract were investigated by an immunohistochemical technique using a carboxylic terminal region-specific monoclonal antibody, 8F9, and a polyclonal antibody, DN-R2. Our results indicated that both the monoclonal and polyclonal antibodies established in this study were highly specific for I-FABP, but not for L-FABP and H-FABP. Especially, the monoclonal antibodies raised against the regional peptides, showed regional specificity for the I-FABP molecule. Immunoreactivity of I-FABP was demonstrated in the mucosal epithelium of the jejunum and ileum by immunohistochemical staining, and the immunoreactivity was based on the presence of the whole I-FABP molecule but not the presence of any precursors or degradation products containing a carboxylic terminal fragment. It is concluded that some of these monoclonal and polyclonal antibodies, such as 8F9, 4205, and DN-R2, will be suitable for use in research on the immunochemistry and clinical chemistry of I-FABP because those antibodies can recognize both types of native and denatured I-FABP. In order to detect I-FABP in blood samples, it is essential to use this type of antibody, reactive to native type of I-FABP. It is anticipated that, in the near future, such a method for measuring I-FABP will be developed as a useful tool for diagnosing intestinal ischemia by using some of these antibodies.

Effect of loss of heterozygosity of the c-kit gene on prognosis after hepatectomy for metastatic liver gastrointestinal stromal tumors.

The authors have previously reported that loss of heterozygosity (LOH) of the c-kit gene could be responsible for the gain in high proliferative activity in some gastrointestinal stromal tumors (GIST), resulting in enhanced metastatic potential. In the present study, an attempt was made to identify the factors that might predict the postoperative prognosis of patients with metastatic liver GIST. The clinicopathologic or genetic features of resected liver GIST in 14 patients who had undergone a hepatectomy for metachronous liver metastases and who had not received adjuvant imatinib treatment were examined. LOH of the c-kit gene was observed in seven of 12 metastatic liver GIST (58.3%), of which DNA suitable for testing could be extracted. Ten patients had recurrence after hepatectomy and four had none. The median post-recurrent disease-free survival (PRDFS) after hepatectomy was 27.5 months (range 8-104). The tumor-specific PRDFS was examined using clinicopathologic features, c-kit mutation and LOH of the c-kit gene. No single clinicopathologic or genetic finding was significantly associated with PRDFS. However, patients with 'Ki67 labeling index <5% and LOH(-)' had a significantly longer PRDFS than those with 'Ki67 >/=5% or LOH(+)' (P = 0.032), and there was no correlation between the presence of LOH of the c-kit gene and the Ki67 labeling index. LOH of the c-kit gene in metastatic liver seems to be a common event, and LOH of the c-kit gene in resected liver GIST may be a helpful factor in the prediction of the post-recurrent prognosis of patients with liver metastasis.

Mucin expression, p53 overexpression, and peritumoral lymphocytic infiltration of advanced colorectal carcinoma with mucus component: is mucinous carcinoma a distinct histological entity?

Mucinous carcinoma of the colorectum is conventionally defined as carcinoma with an interstitial mucus component (MC) that occupies more than 50% of the tumor tissue. To examine the validity of this definition, we quantified the ratio between the area of MC and the total area of carcinoma (MC ratio) in 152 advanced colorectal carcinomas, and investigated whether MUC1, MUC2 and MUC5AC mucin expression, frequency of p53 overexpression, and peritumoral lymphocytic infiltration (PLI) of tumors differ in the MC ratio. Samples were classified into MC ratios of >50% (n=30), 10-50% (n=24), <10% (n=22), and 0% (n=76). Carcinomas with MC commonly possessed the MUC2+ phenotype (90.9-100%), and 76.6-83.3% possessed either the MUC2+/MUC5AC+/MUC1+ or the MUC2+/MUC5AC-/MUC1+ phenotype. Carcinoma without MC (MC ratio of 0%) was typically the MUC2- phenotype (89.5%). Frequencies of p53 overexpression of carcinomas with MC were significantly lower compared to those without MC (21-27% vs. 55%). PLI was observed in 0-4% of carcinomas with MC, but was observed in 17% of carcinomas without MC. These results indicate that colorectal carcinomas with MC can be grouped together as goblet cell type (MUC2+) carcinoma. These data also suggest that such carcinomas may have a common genetic background and alteration of immune responsiveness. Therefore, separately classifying carcinomas with an MC ratio of more than 50% as an independent histological type may be invalid, and re-evaluation of the histological classification of colorectal carcinoma may be required.

Two cases of gastrointestinal stromal tumor of the stomach with lymph node metastasis.

Lymph node metastasis from gastrointestinal stromal tumor (GIST) is quite rare. We report two cases of gastric GIST with nodal metastases and results of their mutation analyses. In the first case (78-year-old male), a mass 4.0 cm in size was located at the gastric cardia. Proximal gastrectomy was performed. In the other case (40-year-old female), the gastric tumor was 2.5 cm in size. Computed tomography scan revealed a hepatic metastasis. Imatinib mesylate was administered as primary treatment, at the patient's preference, but the tumors exhibited no response. Wedge resection of the stomach and partial hepatectomy were performed. In both cases, histological examination revealed that the tumors consisted of spindle cells. In the former case, there was an isolated lymph node metastasis at the right cardia. In the latter, three of 5 sampled nodes adjacent to the tumor were positive. In both cases, immunohistochemical analyses showed that primary and metastatic tumors were diffusely positive for CD117 and CD34 and negative for desmin and S100-protein. In the former case, there was a deletion mutation in CD117 exon 11, the most common genotype in GIST. In the latter, there were no detectable mutations in CD117 or platelet-derived growth factor receptor alpha.

Co-expression of gastric and biliary phenotype in pyloric-gland type adenoma of the gallbladder: immunohistochemical analysis of mucin profile and CD10.

Pyloric-gland type adenoma of the gallbladder is formed by proliferation of glands resembling pyloric glands, morphologically. No previous report has described the cellular phenotype and differentiation of pyloric-gland type adenoma of the gallbladder, using CD10 as a marker of proper biliary phenotype. Immunostainings were performed for mucin markers such as MUC5AC, human gastric mucin (HGM) for gastric foveolar type epithelium, MUC6, M-GGMC-1 for pyloric-gland type and MUC2 for intestinal goblet-cell type, and for CD10 as a proper biliary type marker on 58 pyloric-gland type adenomas of the gallbladder, as well as for p53, Ki-67 and CDX2. The percentage (X) of reactive cells in relation to the total number of tumor cells was estimated semi-quantitatively, and divided into four categories: X=0% (negative), 0%or=30%. CDX2 expression was considered to be positive when the percentage of positively stained cells was >or=10%. Out of the 58 pyloric-gland type adenomas, >or=30% of adenoma cells were positive for MUC5AC in 22 (38%) tumors, HGM in 29 (50%), MUC6 in 58 (100%), M-GGMC-1 in 54 (93%), MUC2 in none (0%), and CD10 in 20 (34%). MUC6 (P<0.001) and M-GGMC-1 (P<0.001) mucins were detected more frequently in pyloric-gland type adenomas, and CD10 expression was significantly decreased, compared with normal gallbladder epithelium (P=0.006). P53 overexpression was not found in any of the 58 tumors, including two adenomas with carcinomatous foci. The mean number of Ki-67-positive cells was 10.3+/-5.8%. CDX2 expression was judged as negative in all 58 pyloric-gland type adenomas. In pyloric-gland type adenomas of the gallbladder, expression of pyloric-gland type mucins was observed with a high frequency, whereas intestinal goblet-cell mucins were rarely seen. In addition, co-expression of gastric foveolar type mucins and CD10 was also demonstrated. Pyloric-gland type adenomas of the gallbladder show a differentiation toward pyloric glands in terms of immunohistochemistry, as well as morphology, accompanied by co-expression of gastric foveolar and native biliary phenotypes.