Collagenous gastroduodenitis coexisting repeated Dieulafoy ulcer: A case report and review of collagenous gastritis and gastroduodenitis without colonic involvement.

Collagenous gastritis (CG) is a rare disorder characterized by the thick collagenous subepithelial bands associated with mucosal inflammation. There have been approximately fifty reports in the literature since it was first described in 1989. According to previous reports, CG is heterogeneous and classified into two groups-(1) cases limited to the gastric mucosa in children or young adults, and (2) CG associated with collagenous colitis in elderly adults presenting with chronic watery diarrhea. In Japan, only nine previous cases were reported, and all of them were young adults. We report a case of CG with collagenous duodenitis in a 22-year-old female. She had repeated upper gastrointestinal bleeding from a Dieulafoy lesion of the fornix, but had no symptoms of malabsorption or diarrhea. Endoscopic findings revealed striking nodularity with a smooth islet-shaped normal area in the antrum and the body. The pathological findings of nodular mucosa showed the deposition of collagen bands just under the mucoepithelial lesion. In addition, she had collagenous duodenitis in part of the bulbs, and a colonoscopy showed no abnormalities. We provide a literature review of CG and collagenous gastroduodenitis without colonic involvement.

Hyperfractionated concomitant boost proton beam therapy for esophageal carcinoma.

PURPOSE: To evaluate the efficacy and safety of hyperfractionated concomitant boost proton beam therapy (PBT) for patients with esophageal cancer. METHODS AND MATERIALS: The study participants were 19 patients with esophageal cancer who were treated with hyperfractionated photon therapy and PBT between 1990 and 2007. The median total dose was 78 GyE (range, 70-83 GyE) over a median treatment period of 48 days (range, 38-53 days). Ten of the 19 patients were at clinical T Stage 3 or 4. RESULTS: There were no cases in which treatment interruption was required because of radiation-induced esophagitis or hematologic toxicity. The overall 1- and 5-year actuarial survival rates for all 19 patients were 79.0% and 42.8%, respectively, and the median survival time was 31.5 months (95% limits: 16.7- 46.3 months). Of the 19 patients, 17 (89%) showed a complete response within 4 months after completing treatment and 2 (11%) showed a partial response, giving a response rate of 100% (19/19). The 1- and 5-year local control rates for all 19 patients were 93.8% and 84.4 %, respectively. Only 1 patient had late esophageal toxicity of Grade 3 at 6 months after hyperfractionated PBT. There were no other nonhematologic toxicities, including no cases of radiation pneumonia or cardiac failure of Grade 3 or higher. CONCLUSIONS: The results suggest that hyperfractionated PBT is safe and effective for patients with esophageal cancer. Further studies are needed to establish the appropriate role and treatment schedule for use of PBT for esophageal cancer.

Surface X-ray scattering of stepped surfaces of platinum in an electrochemical environment: Pt(331) = 3(111)-(111) and Pt(511) = 3(100)-(111).

Real surface structures of the high-index planes of Pt with three atomic rows of terraces (Pt(331) = 3(111)-(111) and Pt(511) = 3(100)-(111)) have been determined in 0.1 M HClO(4) at 0.1 and 0.5 V(RHE) with the use of surface X-ray scattering (SXS). The surfaces with two atomic rows of terraces, Pt(110) = 2(111)-(111) and Pt(311) = 2(100)-(111) = 2(111)-(100), are reconstructed to a (1 × 2) structure according to previous studies. However, the surfaces with three atomic rows of terraces have pseudo-(1 × 1) structures. The interlayer spacing between the first and the second layers, d(12), is expanded 13% on Pt(331) compared to that of the bulk, whereas it is contracted 37% on Pt(511). The surface structures do not depend on the applied potential on either surface.

Clinical results of proton-beam therapy for locoregionally advanced esophageal cancer.

PURPOSE: To evaluate the efficacy and safety of proton-beam therapy for locoregionally advanced esophageal cancer. PATIENTS AND METHODS: The subjects were 51 patients with esophageal cancer who were treated between 1985 and 2005 using proton beams with or without X-rays. All but one had squamous cell carcinoma. Of the 51 patients, 33 received combinations of X-rays (median 46 Gy) and protons (median 36 GyE) as a boost. The median total dose of combined X-rays and proton radiation for these 33 patients was 80 GyE (range 70-90 GyE). The other 18 patients received proton-beam therapy alone (median 79 GyE, range 62-98 GyE). RESULTS: Treatment interruption due to radiation-induced esophagitis or hematologic toxicity was not required for any patient. The overall 5-year actuarial survival rate for the 51 patients was 21.1% and the median survival time was 20.5 months (95% confidence interval 10.9-30.2). Of the 51 patients, 40 (78%) showed a complete response within 4 months after completing treatment and seven (14%) showed a partial response, giving a response rate of 92% (47/51). The 5-year local control rate for all 51 patients was 38.0% and the median local control time was 25.5 months (95% confidence interval 14.6-36.3). CONCLUSION: The results suggest that proton-beam therapy is an effective treatment for patients with locally advanced esophageal cancer. Further studies are required to determine the optimal total dose, fractionation schedules, and best combination of proton therapy with chemotherapy.

Deletion of nuclear factor-E2-related factor-2 leads to rapid onset and progression of nutritional steatohepatitis in mice.

Oxidative stress is a critical mediator in liver injury of steatohepatitis. The transcription factor Nrf2 serves as a cellular stress sensor and is a key regulator for induction of hepatic detoxification and antioxidative stress systems. The involvement of Nrf2 in defense against the development of steatohepatitis remains unknown. We aimed to investigate the protective roles of Nrf2 in nutritional steatohepatitis using wild-type (WT) and Nrf2 gene-null (Nrf2-null) mice. WT and Nrf2-null mice were fed a methionine- and choline-deficient (MCD) diet for 3 and 6 wk, and the liver tissues were analyzed for pathology and for expression levels of detoxifying enzymes and antioxidative stress genes via the Nrf2 transcriptional pathway. In WT mice fed an MCD diet, Nrf2 was potently activated in the livers, and steatohepatitis did not develop over the observation periods. However, in Nrf2-null mice fed an MCD diet, the pathological state of the steatohepatitis was aggravated in terms of fatty changes, inflammation, fibrosis, and iron accumulation. In the livers of the Nrf2-null mice, oxidative stress was significantly increased compared with that of WT mice based on the increased levels of 4-hydroxy-2-nonenal and malondialdehyde. This change was associated with the decreased levels of glutathione, detoxifying enzymes, catalase, and superoxide dismutase activity. Correlating well with the liver pathology, the mRNA levels of factors involved in fatty acid metabolism, inflammatory cytokines, and fibrogenesis-related genes were significantly increased in the livers of the Nrf2-null mice. These findings demonstrate that Nrf2 deletion in mice leads to rapid onset and progression of nutritional steatohepatitis induced by an MCD diet. Activation of Nrf2 could be a promising target toward developing new options for prevention and treatment of steatohepatitis.

Mutagenesis studies of human cystathionine beta-synthase: residues important for heme binding and substrate interactions.

Human cystathionine beta-synthase (CBS) is a pyridoxal 5'-phosphate (PLP) dependent hemoprotein, which catalyzes the condensation of serine and homocysteine. Our mutagenesis studies suggest that Arg-266 is important to sense structural changes in heme-binding site, and that Gln-222 as well as Tyr-223 are involved in interactions with substrates.

Peroxiredoxin I protects gastric mucosa from oxidative injury induced by H. pylori infection.

BACKGROUND AND AIM: Helicobacter pylori (H. pylori) infection enhances the production of reactive oxygen species and peroxynitrite, thereby resulting in oxidative tissue damage. In this study, we examined the role of peroxiredoxin I (Prx I), a stress-induced antioxidant enzyme, in protecting gastric mucosa from H. pylori-induced gastric mucosal injury. METHODS: Wild type (Prx I(+/+)) and Prx I-deficient type (Prx I(-/-)) mice were maintained for 2 to 12 months with or without infection of H. pylori, Sydney strain-1. Gastric mucosal expression of Prx I was assessed by immunoblot analysis and immunohistochemistry. The degree of gastritis was evaluated by the updated Sydney system and by mucosal levels of inflammatory cytokines (MIP-2, IL-1beta, and TNF-alpha). Oxidative DNA injury and apoptosis were analyzed by mucosal level of 8-hydroxy-2'-deoxyguanosine, and the number of apoptotic cells stained with a single-stranded DNA antibody, respectively. RESULTS: H. pylori infection upregulated gastric mucosal Prx I expression in the Prx I(+/+) but not the Prx I(-/-) mice. H. pylori infection also induced more severe gastritis and a more prominent increase in MIP level, more marked oxidative DNA injury, and apoptosis in the Prx I(-/-) than the Prx I(+/+) mice. In the absence of H. pylori infection, no changes were demonstrated in gastric mucosa in either the Prx I(+/+) or the Prx I(-/-) mice. CONCLUSION: These data suggest that H. pylori infection upregulates gastric mucosal Prx I expression, and further, that Prx I plays an important role in gastric mucosal protection against oxidative injury induced by H. pylori infection.

Neoplastic transformation and induction of H+,K+ -adenosine triphosphatase by N-methyl-N'-nitro-N-nitrosoguanidine in the gastric epithelial RGM-1 cell line.

N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induces gastric cancer in animal models. We established an MNNG-induced mutant of the rat murine RGM-1 gastric epithelial cell line, which we named RGK-1, that could be used as an in vitro model of gastric cancer. This cell line showed signs of neoplasia and transformation, in that it lost contact inhibition and formed tumors in nude mice. The mutant cells also expressed parietal cell-specific H(+),K(+)-adenosine triphosphatase (H(+),K(+)-ATPase), which parent RGM-1 did not. The results suggested that parent RGM-1 cells were gastric progenitor cells. This mutant RGK-1 cell line will contribute to future investigation on gastric carcinogenesis and to the development of other pathophysiologic fields.

Cellular membrane fluidity measurement by fluorescence polarization in indomethacin-induced gastric cellular injury in vitro.

BACKGROUND: Gastric complications of indomethacin involve generation of reactive oxygen species, which induce gastric mucosal injury via lipid peroxidation of cell membranes. Peroxidation by reactive oxygen species alters the amounts of unsaturated fatty acids in the cell membrane and thus affects membrane fluidity. Indomethacin-induced lipid peroxidation can thus be detected by measuring cellular membrane fluidity by the fluorescence polarization (FP) method. The aim of this study was to elucidate the usefulness of the FP method for detecting indomethacin-induced gastric cellular injury in RGM-1 cells. METHODS: Indomethacin-treated RGM-1 cells were investigated by conventional cytotoxicity assay, fluorometry of diphenyl-1-pyrenylphosphine (DPPP) to detect lipid peroxidation, and FP. The effects of both a radical scavenger and an initiator on membrane fluidity change (MFC) in RGM-1 cells were examined. The sensitivity of FP in detecting cellular injury was compared with those of DPPP fluorometry and conventional cytotoxicity measurements. RESULTS: Indomethacin caused an increase in MFC as determined by FP before cytotoxicity was detected by conventional methods. The increase in MFC was associated with increased membrane phospholipid peroxidation (MPP) but not with a prostaglandin deficiency, and the increases in both MFC and MPP were prevented by vitamin E. CONCLUSIONS: The FP method is potentially useful for detecting cellular injury in vitro.

In situ surface X-ray scattering of stepped surface of platinum: Pt(311).

Surface structure of a stepped surface of Pt, Pt(311) (=2(100)-(111)), has been determined under potential control in 0.1 M HClO4 with the use of in situ surface X-ray scattering (SXS). The crystal truncation rods (CTRs) are reproduced well with the (1x2) missing-row model. Relaxation of surface layers, which is observed on the low-index planes of Pt, is not found on Pt(311) in the "adsorbed hydrogen region". CTRs at 0.10 (RHE) have the same feature as those at 0.50 V, showing that the surface layers of Pt(311) have no potential dependence. Scanning tunneling microscopy (STM) also supports the (1x2) structure of Pt(311) in 0.1 M HClO4.

Geranylgeranylacetone protects the human gastric mucosa from diclofenac-induced injury via induction of heat shock protein 70.

BACKGROUND/AIM: Geranylgeranylacetone (GGA) enhances gastric mucosal protection against nonsteroidal anti-inflammatory drugs by upregulating mucosal heat shock proteins (HSP), but the effects of GGA on the human gastric mucosa have not been well examined. This study was conducted to determine whether a clinical dose of GGA protects the human gastric mucosa from diclofenac (DIC)-induced gastric mucosal injury. METHODS: The study group comprised 40 healthy volunteers: 20 subjects were randomly assigned to take either placebo (lactose 1.5 g/day) or GGA (150 mg/day) for 2 weeks (study 1), and 20 subjects were assigned to take DIC (75 mg/day) plus placebo (lactose 1.5 g/day) or DIC (75 mg/day) plus GGA (150 mg/day) for 2 weeks (study 2). In both studies, gastroscopic biopsy specimens were obtained before and after treatment. Mucosal HSP70 expression and DNA damage were analyzed by measuring the levels of HSP70 and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OHdG), respectively. RESULTS: In study 1, GGA increased the mucosal HSP70 expression without increasing the 8-OHdG production. In study 2, DIC treatment increased the 8-OHdG production, whereas the combination of GGA and DIC enhanced the HSP70 expression and attenuated the increase in 8-OHdG induced by DIC. CONCLUSION: The clinical dose of GGA enhanced the gastric mucosal HSP70 expression and inhibited the DIC-induced gastric mucosal damage in humans.

Hyperosmotic stress enhances interleukin-1beta expression in Helicobacter pylori-infected murine gastric epithelial cells in vitro.

BACKGROUND AND AIM: Gastric cancer is associated not only with Helicobacter pylori (H. pylori) infection, but also with the intake of a high salt diet. Interleukin-1beta (IL-1beta) is highly expressed in H. pylori-infected gastric mucosa. The aim of the present study was to determine if hyperosmotic stress induces IL-1beta expression in gastric epithelial cells in vitro. METHOD: Murine gastric epithelial cells, GSM06, were cultured with or without H. pylori (Sydney strain-1) at different osmolarities in the range of 300-450 mOsM. Expressions of IL-1beta mRNA and mature IL-1beta protein were evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and an IL-1beta enzyme-linked immunosorbent assay (ELISA), respectively. IL-1beta converting enzyme (ICE) activity was measured by an ICE colorimetric assay. Apoptosis was evaluated by a single stranded-DNA assay. RESULTS: Addition of H. pylori at 300 mosM caused significant increases in IL-1beta mRNA, IL-1beta protein, ICE activity and apoptosis. Hyperosmotic stress alone also caused upregulation of IL-1beta mRNA and IL-1beta protein, enhanced ICE activity and accelerated apoptosis. Hyperosmotic stress accentuated the increases in IL-1beta mRNA, IL-1beta protein, ICE activity and apoptosis induced by H. pylori alone. Enhancement of IL-1beta protein release induced by hyperosmotic stress was significantly attenuated by an ICE inhibitor, Z-YVAD-FMK. CONCLUSIONS: Hyperosmotic stress enhances the release of bioactive mature IL-1beta protein in H. pylori-infected gastric epithelial cells, in part by upregulating IL-1beta mRNA expression, and in part by enhancing ICE activity. These results may explain the mechanisms by which chronic intake of a high salt diet increases the risk of gastric cancer among H. pylori-infected human subjects.

Influence of chemotherapeutic agents and cytokines on the expression of 5-fluorouracil-associated enzymes in human colon cancer cell lines.

BACKGROUND: Several studies have demonstrated that intratumoral expression of catabolizing and anabolizing enzymes for 5-fluorouracil (5-FU) is important in the response of cancers to 5-FU-based chemotherapy. We investigated the influence of other chemotherapeutic agents or cytokines, which are often administered for enhancing the efficacy of 5-FU, on the tumoral expression of 5-FU-associated enzymes, i.e., dihydropyrimidine dehydrogenase (DPD), thymidylate synthase (TS), orotate phosphoribosyl transferase (OPRT), and thymidine phosphorylase (TP). METHODS: Human colon cancer cell lines (HT-29, Caco-2, and DLD-1) were incubated with 5-FU and with 5-FU combined with cisplatin, camptothecin, paclitaxel, mitomycin C, interferon, or TNF-related apoptosis-inducing ligand. mRNA expression of 5-FU-associated enzymes was assessed by real-time PCR. Activity of each enzyme and intracellular 5-FU accumulation after incubation with such agents were also evaluated. RESULTS: Each agent had a synergistic effect on the cytotoxicity of 5-FU. All chemotherapeutic agents other than cytokines induced marked alteration of the mRNA expression profile of 5-FU-associated enzymes; depression of DPD, elevation of TS, and slight suppression of OPRT and TP. In accordance with mRNA expression, enzyme activity of DPD was significantly depressed by such agents. Furthermore, although 5-FU itself increased DPD mRNA expression, a mechanism considered to be related to the acquisition of 5-FU resistance, the addition of cisplatin or camptothecin significantly inhibited the 5-FU-induced elevation of DPD. CONCLUSIONS: 5-FU-associated enzymes in colon cancer cells were greatly influenced by various chemotherapeutic agents; in particular, DPD expression was depressed. These results appear important in planning chemotherapy and also in understanding the development of adverse effects of 5-FU.

Alteration of intestinal epithelial function by intraepithelial lymphocyte homing.

BACKGROUND: Intimate cross-talk may take place between intestinal epithelial cells and intraepithelial lymphocytes (IEL). The purpose of this study was to analyze the influence of lymphocyte migration into the epithelium on epithelial function, using an in vitro "IEL homing" model. METHODS: Molecular expression on epithelial cells was analyzed by flow cytometry. The barrier function of the epithelial monolayer was assessed by transepithelial electrical resistance. Cytokine production was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: (1) IEL homing into the epithelia induced significant phenotypic changes in epithelial cells; upregulation of MHC class I, and II, intercellular adhesion molecule (ICAM)-1, and CD44. IEL-derived interferon-gamma (IFN-gamma) could partially account for this alteration, as a neutralizing antibody (Ab) against IFN-gamma inhibited the upregulation of these molecules, except for CD44. (2) A marked fall in transepithelial electrical resistance was observed 4 h after IEL homing started, and Ab against IFN-gamma slightly inhibited this fall in resistance. (3) The production of interleukin (IL)-8 and IFN-gamma inducible protein-10 (IP-10), but not transforming growth factor (TGF)-beta1 or tumor necrosis factor (TNF)-alpha, in the epithelial monolayer was markedly induced after IEL homing in a basolaterally polarized fashion. IEL-conditioned media also induced the production of these cytokines in epithelial cells, thus suggesting that IEL-derived soluble factor(s) induce epithelial chemokine production. CONCLUSIONS: Under inflammatory conditions, IEL obviously interact with epithelial cells and upregulate adhesion molecules, alter barrier function, and enhance chemokine production. Because such alterations may increase epithelial permeability to luminal antigens or accelerate the migration of other inflammatory cells, our results suggest that IEL have a critical role in mucosal immunity.

Rebamipide significantly inhibits indomethacin-induced mitochondrial damage, lipid peroxidation, and apoptosis in gastric epithelial RGM-1 cells.

Nonsteroidal antiinflammatory drugs (NSAIDs) cause complications such as gastrointestinal injury. NSAIDs were recently reported to cause mitochondrial injury: to dissipate the mitochondrial transmembrane potential (MTP), and to induce mitochondrial permeability transition pore (PTP), which liberates cytochrome c. This enzyme generates reactive oxygen species (ROS) thereby triggers caspase cascade and cellular lipid peroxidation, resulting in cellular apoptosis. However, the mechanism of this NSAID-induced MTP's role in cellular apoptosis remains unknown. Rebamipide, an antiulcer drug, is reported to scavenge ROS and to show the protective effects on indomethacin-induced tissue peroxidations. Since cytochrome c and its generation of ROS are involved in indomethacin-induced cellular apoptosis, rebamipide may attenuate mitochondrial damage. The aim of this study was to elucidate whether indomethacin induces both the MTP decrease and cellular apoptosis, and the effect of rebamipide on these phenomena. We examined the effect of rebamipide on 1) MTP change, 2) lipid peroxidation, 3) apoptosis, and 4) caspase activation using gastric mucosal epithelial cell-line treated with indomethacin. With a specially designed fluorescence analyzing microscope system, MTP change, cellular lipid peroxidation, and cellular apoptosis were investigated with the small star, filled following fluorescent dyes, MitoRed, DPPP, and Hoechst 33,258, respectively. Indomethacin treatment decreased MTP but increased both cellular lipid peroxidation and cellular apoptosis via caspase 3 and 9 activation. Rebamipide clearly inhibited these phenomena {in vitro}. We demonstrated that fluorescent dyes such as MitoRed, DPPP, and Hoechst 33,258 are useful indicators for detecting oxidative cellular injuries in living cells. Rebamipide exerts a protective effect on mitochondrial membrane stability in gastric epithelial cells.

Efficacy of endoscopic nasobiliary drainage for the prevention of pancreatitis after papillary balloon dilatation: a pilot study.

OBJECTIVE: Endoscopic papillary balloon dilatation (EPBD) has been reported to increase the risk of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (4%-11%). Based on the hypothesis that performing endoscopic nasobiliary drainage (ENBD) could prevent this complication, we performed EPBD combined with ENBD (EPBD/ENBD) and analyzed the risk of pancreatitis. METHODS: Thirty-four patients underwent EPBD followed by ENBD for common bile duct stone(s). Serum amylase levels the following morning and incidence of pancreatitis were compared with those previously reported and with complications of simple diagnostic ERCP performed in our institution. RESULTS: After EPBD/ENBD, amylase levels the following morning were 214.5 +/- 152.9 U/L, and no cases developed pancreatitis or hyperamylasemia (>3 times normal). These outcomes were favorable compared with previous EPBD reports. Furthermore, despite the stress of EPBD/ENBD after ERCP, these outcomes were better, even compared with simple ERCP performed at our institution [amylase levels: 318.7 +/- 475.2 U/L; hyperamylasemia: 16.5% (P = 0.006); pancreatitis: 7.1%]. CONCLUSION: Although EPBD has been regarded as a risk factor for post-ERCP pancreatitis, our results suggest the possibility that application of ENBD after EPBD decreases the incidence of pancreatitis and should be studied further. We speculate that ENBD itself prevents pancreatic duct obstruction by residual stones or papillary edema.

Clinical results of proton beam therapy for cancer of the esophagus.

PURPOSE: To present the results of proton beam therapy for patients with esophageal cancer. METHODS AND MATERIALS: This study reviewed 46 patients with esophageal cancer who were treated between 1985 and 1998 using proton beams with or without X-rays. All patients had locoregionally confined disease; all but one had squamous cell carcinoma. Of the 46 patients, 40 received combinations of X-rays (median, 48 Gy) and protons (median, 31.7 Gy) as a boost. The median total dose of combined X-ray and proton radiation for the 40 patients was 76.0 Gy (range, 69.1-87.4 Gy). The remaining 6 patients received only proton beam therapy (median, 82.0 Gy; range, 75-89.5 Gy). RESULTS: The 5-year actuarial survival rate for the 46 patients, patients with T1 (n = 23), and those with T2-T4 (n = 23) was 34%, 55%, and 13%, respectively. The 5-year disease-specific survival rate for the 46 patients, those with T1, and those with T2-T4 was 67%, 95%, and 33%, respectively. The 5-year local control rate for patients with T1 and T2-T4 lesions was 83% and 29%, respectively. The site of the first relapse was locoregional for 16 patients and distant organs for 2 patients. CONCLUSION: The results suggest that proton beam therapy is an effective treatment for patients with locally confined esophageal cancer. Additional studies are required to determine the optimal total dose, fractionation schedule, and best combinations of protons and conventional X-rays with or without chemotherapy.

Expression of MUC1 recognized by monoclonal antibody MY.1E12 is a useful biomarker for tumor aggressiveness of advanced colon carcinoma.

To address the need for new prognostic parameters in advanced colon carcinoma that could add insights into the aggressiveness of tumors, the expression levels of MUC1 recognized by a monoclonal antibody (mAb) MY.1E12 in archival specimens from 123 Japanese patients with colon carcinomas were evaluated by immunohistochemistry to correlate the results with clinicopathological characteristics. The localization of mAb MY.1E12-reactive-MUC1 (MY.1E12-MUC1) was classified into apical, cytoplasmic and stromal types based on the predominant cellular distribution. The MUC1 mRNA levels revealed by in situ hybridization were not a determinant for the localization types of MY.1E12-MUC1. Immunostaining of MY.1E12-MUC1 was recognized in the cancerous epithelia of pT1 carcinoma in 61%, pT2 in 78%, pT3 in 98% and pT4 in 90% of the cases at the deepest invading sites. At the deepest invading sites, apical-type localization was found to predominate in pT1 carcinoma, but stromal-type localization was found to increase in pT2-4 carcinomas in parallel with the depth of invasion. The frequency of synchronous distant organ metastasis at the time of diagnosis tended to be higher in cases of pT3 and pT4 carcinomas in the stromal-type localization-dominant group than in cases in the apical-type localization-dominant group. The post-surgical survival outcome of cases of pT3 and pT4 carcinomas was significantly poorer in the former than in the latter (P = 0.002). The stromal-type localization of MY.1E12-MUC1 may be a phenotype serving as a unique biological feature associated with the tumor aggressiveness of advanced colon carcinoma.