Cytokeratin Type Research Articles

Does vimentin help to delineate the so-called 'basal type breast cancer'?

BackgroundVimentin is one of the cytoplasmic intermediate filament proteins which are the major component of the cytoskeleton. In our study we checked the usefulness of vimentin expression in identifying cases of breast cancer with poorer prognosis, by adding vimentin to the immunopanel consisting of basal type cytokeratins, estrogen, progesterone, and HER2 receptors.Methods179 tissue specimens of invasive operable ductal breast cancer were assessed by the use of immunohistochemistry. The median follow-up period for censored cases was 90 months.Results38 cases (21.2%) were identified as being vimentin-positive. Vimentin-positive tumours affected younger women (p = 0.024), usually lacked estrogen and progesterone receptor (p < 0.001), more often expressed basal cytokeratins (<0.001), and were high-grade cancers (p < 0.001). Survival analysis showed that vimentin did not help to delineate basal type phenotype in a triple negative (ER, PgR, HER2-negative) group. For patients with 'vimentin or CK5/6, 14, 17-positive' tumours, 5-year estimated survival rate was 78.6%, whereas for patients with 'vimentin, or CK5/6, 14, 17-negative' tumours it was 58.3% (log-rank p = 0.227).ConclusionWe were not able to better delineate an immunohistochemical definition of basal type of breast cancer by adding vimentin to the immunopanel consisted of ER, PgR, HER2, CK5/6, 14 and 17 markers, when overall survival was a primary end-point.

The apical mitochondria-rich cells of the mammalian epididymis.

The morphology and function of the apical mitochondria-rich cells in the mammalian ductus epididymidis epithelium are revised. These cells are similar in all mammalian species studied. Apical mitochondria-rich cells are scarce (1-5 cells/100 principal cells) and are mainly found in the initial epididymal segments. Their morphology varies from slender cells that extend from the basal lamina to the epididymal lumen, to round cells that protrude into the lumen and are not in contact with the basal lamina. Their cytoplasm is more electron-dense than that of principal cells and contains more mitochondria which, in some species, are surrounded by rough endoplasmic reticulum cisternae. The adluminal cytoplasm displays a few short microvilli and contains many acid phosphatase positive vesicles. Apical mitochondria-rich cells differ from the principal cells in some histochemical features such as: (a) different lectin-staining pattern; (b) more intense reaction to the enzymatic activities: carbonic anhydrase, Ca(2+)-ATPase, peanut-agglutinin-sialidase, NADP dehydrogenase, succinate dehydrogenase, alpha-galactosidase and beta-galactosidase; (c) more intense immunoreaction to several cytokeratin types and to estradiol-related receptor protein; (d) weaker immunoreaction to epithelial membrane antigen and to retinol-binding protein. Although the function of the apical mitochondria-rich cells is still unknown, the following possible functions have been suggested: holocrine secretion; cooperation with the principal cells in epididymal reabsorption of testicular fluid; and acidification of epididymal fluid. Experimental results suggest that differentiation and maintenance of apical mitochondria-rich cells are not under androgen control and that these cells are sensitive to estrogen stimulation.

Composite Carcinoma of the Stomach Associated with Sarcoid-Like Granulomas

Composite glandular/exocrine-endocrine carcinoma of the gastrointestinal tract is a special tumor type composed of common adenocarcinoma and the neuroendocrine component comprising at least one-third of the whole tumor area. These tumors are rare in the stomach and mostly published as case reports. We describe a further case of a 36-year-old man being unique in that it was associated with extensive formation of sarcoid-like granulomas. Tumor consisted of, predominantly poorly differentiated, intestinal-type adenocarcinoma and poorly differentiated neuroendocrine, small cell carcinoma. The adenocarcinomatous and neuroendocrine areas were separated, but closely juxtaposed with focal areas showing gradual transition from one to another. Perigastric lymph node metastases corresponded either to neuroendocrine or adenocarcinomatous component. On immunohistochemistry, the exocrine part was positive for cytokeratin 7, whereas superficial well-differentiated parts showed positivity with cytokeratin 20 as well. The neuroendocrine component was negative with those two types of cytokeratin. Both adenocarcinomatous and neuroendocrine tumor portions showed carcinoembryonic antigen (CEA) immunoexpression. Neuroendocrine markers (chromogranin A, synaptophysin and neuron-specific enolase) were diffusely positive in the neuroendocrine component, and found only in the scattered cells within the neoplastic glands of the adenocarcinoma. Entire gastric mucosa and all perigastric lymph nodes were extensively affected by noncaseating, sarcoid-like granulomas. The absence of any clinical manifestations combined with the negative results of chest radiograph and laboratory test for the serum angiotensin converting enzyme argued against the possibility of systemic sarcoidosis.

Occult very small lung carcinoma with a solitary brain metastasis that is clinically diagnosed as cavernous hemangioma: a case report

The author reports herein a case of occult very small lung carcinoma with a solitary brain metastasis that is clinically diagnosed as cavernous hemangioma, with an emphasis on pathologic findings. A 48-year-old Japanese man was admitted to our hospital complaining of mild paresis of left leg. Brain CT and MRI showed a solitary tumor (2 cm) with features of cavernous hemangioma in the right temporal lobe. Tumorectomy was performed, and it was pathologically undifferentiated carcinoma. An immunohistochemical analysis reveled that the carcinoma cells were positive for four types of pancytokeratin, cytokeratin (CK) 5/6, CK7, CK18, CK19, p63, and Ki-67 (78%). They were negative for high molecular weight CK, CK14, CK20, TTF-1, PE-10, melanosome, S100 protein, EMA, vimentin, CD34, myoglobin, CEA, p53, desmin, α-smooth muscle actin, chromogranin, synaptophysin, CD56, neuron-specific enolase, CD68, KIT, and PDGFRA. The positive CK7 and negative CK20 suggested lung origin, and cytokeratin profiles and positive CK5/6 and p63 suggested a squamous differentiation. The pathological diagnosis was undifferentiated carcinoma with squamous differentiation probably of lung origin. Later, systemic CT, MRI and PET were performed, and they detected a small lung tumor (8 mm) in the right apex. The lung biopsy revealed an undifferentiated carcinoma with focal squamous differentiation; the immunohistochemical findings were the same as those of the brain tumor. These findings suggest that occult very small lung carcinoma can metastasize to brain and such a metastasis may mimic cavernous hemangioma radiologically. Pathologic observations using many antibodies are very useful to determine the origin and histological type in solitary brain nodule.

Pancreatic Acinar Tissue in Liver Explants

Pancreatic acini-like tissue is occasionally seen in the liver. It is uncertain whether its presence represents heterotopia or metaplasia. To gain further insight into this issue, we performed a pathologic and immunohistochemical study in liver explants to identify pancreatic acinar tissue. A total of 382 liver explants transplanted from 1995 to 2000 were examined. Formalin-fixed, paraffin-embedded tissues were stained with hematoxylin-eosin, and immunohistochemical analyses using antibodies against CK7, CK8, and CK19 (biliary type cytokeratins), CD56 (positive in reactive bile ductules), chromogranin A (positive in reactive bile ductules and human oval-like/hepatic progenitor cells), pancreatic amylase, and PDX-1 were performed. The immunohistochemical comparison group consisted of 3 gastric biopsies diagnosed as autoimmune gastritis with pancreatic metaplasia and 3 normal pancreatic tissues from pancreatectomy specimens. Sixteen (4.2%) of 382 liver explants contained pancreatic acini-like tissue. Fifteen of these were cirrhotic livers due to cryptogenic cirrhosis (n=1), primary biliary cirrhosis (n=3), primary sclerosing cholangitis (n=1), chronic hepatitis C-related cirrhosis (n=5), and cirrhosis with hepatitis C and hepatocellular carcinoma (n=5). There was 1 noncirrhotic explant, the result of isoniazid hepatotoxicity. The pancreatic acini-like tissue appeared as small clusters of compactly packed cells that either blended imperceptibly with or were in close proximity to adjacent bile ducts or ductules. The pancreatic acinar tissue was diffusely reactive for amylase, was occasionally positive for keratin 8 and chromogranin A, and was negative for CD56, keratin 7, and keratin 19. Biliary type epithelium (bile ducts and ductules) and the ductules within the acini was always diffusely positive for keratin 7, 8, and 19, occasionally reactive for CD56 and chromogranin A, and typically negative for amylase. Our results collectively indicate that pancreatic acini-like tissue in liver represent aggregates of pancreatic acinar cells admixed with small intra-acinar terminal ductules. Given the close spatial relationship with reactive bile ductules and the apparent transition in immunophenotype from bile ductules to pancreatic acinar tissue, the latter is likely of metaplastic origin derived from a hepatic progenitor lineage.

Enzyme-histochemical studies of griseofulvin-intoxicated mouse livers.

Enzyme-histochemical studies were conducted on livers of mice chronically fed griseofulvin (GF) in order to produce Mallory bodies (MBs) in hepatocytes. The development of MBs is associated with derangement of the immunohistochemically detectable intermediate filament (IF) cytoskeleton of the cytokeratin (CK) type, although no strict correlation between appearance or involution of MBs and the cytoskeletal alterations exists. Since the function of the IF cytoskeleton and the relationship of its disturbance to cell injury is unknown, the aim of the present study was to correlate the activities of several key enzymes of cellular metabolic pathways with the disturbance of the cytoskeleton architecture. For that purpose enzyme-histochemistry in combination with immunohistochemical CK-IF stainings were performed on identical sections. In GF-intoxicated mouse livers the normal topography of enzyme activities was disturbed, but no strict colocalization of enzymatic and cytoskeletal changes was found. Glucose-6-phosphatase, a microsomal enzyme involved in glucose output and gluconeogenesis, showed elevated activity in MB-free hepatocytes with diminished immunostainable CK-IF cytoskeleton refuting the concept of a disability of those cells to export glucose. It could indeed indicate that those cells without MBs are in the state of recovery. However, these cells could also resemble "hyperactive foci". Glycogen was decreased in MB-containing hepatocytes with disturbed cytoskeleton, and this feature favours the assumption of cell degeneration. On the other hand, the mitochondrial marker enzymes, i.e. succinate dehydrogenase, cytochrome-c-oxidase and 3-hydroxybutyrate dehydrogenase, remained unchanged in altered hepatocytes. Alkaline phosphatase activity at the canalicular pole of GF-intoxicated hepatocytes was elevated, indicating cholestatic features associated with this disorder. However, since altered hepatocytes did not show impairment of oxido-reductase activities, a severe impairment of bile secretion as a consequence of cell damage is unlikely. Unchanged or even increased ATPase activity of altered hepatocytes also indicated their sustained metabolic abilities. The results presented provide indirect evidence that hepatocytes with disturbed IF cytoskeleton do not significantly differ from normal cells with respect to oxidative metabolism, fatty acid synthesis and gluconeogenesis. This suggests that alterations of the IF cytoskeleton associated with GF intoxication and MB formation have no significant adverse influence on the metabolic functions of liver cells, as far as can be assessed by evaluation by enzyme-histochemical staining of several key enzymes.

74 POSTER Experimental therapeutic approach of human diffuse large B-cell lymphoma xenografts by doxycycline, alone or in combination with the anti-CD20 chimeric monoclonal antibody rituximab

Primary lymphoma of soft tissue is very rare. A 59-year-old Japanese man presented left leg tumor measuring 3 × 3 × 2 cm without skin ulceration. A large incisional biopsy was performed. It showed atypical lymphoid cell proliferation in subcutaneous tissue next to the fascia. Immunohistochemically, the tumor cells were positive for CD45, CD20, CD79α, λ-chain, and p53 protein. The Ki-67 labeling was 100%. In contrast, they were negative for various types of cytokeratins, epithelial membrane antigen, CD3, CD30, CD10, CD45RO, TdT, κ-chain, CD56, bcl-2, bcl-6 and MUM1. A diagnosis of diffuse large B-cell lymphoma (DLBCL) of non-germinal center type (DLBCL-non-GC) of soft tissue was performed. Systemic investigation using various imaging modalities including CT, MRI and Ga-scintigraphy revealed lymph nodes swelling in the inguinal region. The patient was treated by R-CHOP chemotherapy and radiation. The tumor and lymph nodes were markedly reduced in size. He is now alive with disease two years after the first manifestation.

Intrahepatic multicystic biliary hamartoma: report of a case

Multicystic biliary hamartoma is a very rare hamartomatous nodule in the liver, which has recently been described as a new category of hepatic nodular lesion. We herein report the case of a 55-year-old man histopathologically diagnosed with this entity following surgery. A solitary multilocular lesion in the liver was pointed out by ultrasonography during a systemic examination for a positive HBs antigen. This nodule could not be definitively diagnosed by radiologic modalities, including computed tomography, magnetic resonance imaging and arteriography. The patient underwent a partial resection of the posterior segment of the liver. The nodule was a localized lesion which measured 5 x 3 cm at the widest point and displayed a honeycomb appearance. Histologically, it consisted of ductal structures, periductal glands, fibrous connective tissues containing blood vessels, and bile-like materials and xanthogranulomatous inflammation within some ducts. Liver parenchyma was not present in the nodule and the bile ducts were not dilated in the background liver. The ductal epithelium expressed biliary type cytokeratins (CK7 and 19) in immunohistochemical studies. These histopathological features were consistent with multicystic biliary hamartoma, and we discuss this rare case in detail in this report.

Biliary-Type Cytokeratin Pattern in a Canine Isolated Perfused Liver Transplantation Model

Ischemia-reperfusion (I/R) injury in liver transplantation units and the influence of I/R injury on bile flow dynamics is being intensely investigated in various animal models, but the expression of intracellular intermediate filaments of biliary type as an early sign of cholestasis has not been yet explored. We studied the hepatic elimination kinetics of indocyanine green (ICG), an exclusively biliary excreted cholephilic dye, and the functional and morphological integrity of liver cells in a canine liver transplantation model following I/R. During reperfusion following cold ischemia, we evaluated the ICG excretion curves, biochemical signs of liver damage, the bile canaliculus of the hepatocytes by electron microscopy, and the expression of intermediate filaments of cytokeratin type by immunohistochemistry. Impairment of the biliary ICG excretion was directly related to ischemia time, but hepatocellular ICG uptake and bile flow rate were not significantly reduced. Liver enzymes increased as early as 6 h of ischemia and hepatocytes showed an increase of the bile canaliculus area. This was correlated to a membranous to cytoplasmatic staining of the cytoskeleton of the hepatocytes. To the best of our knowledge, this is the first evidence of cholestatic changes starting early following cold ischemia in a canine isolated perfused liver transplantation model despite prompt recovery of the bile flow.

Immunopathological Patterns of the Stomach in Adenocarcinoma of the Esophagus, Cardia, and Gastric Antrum: Gastric Profiles in Siewert Type I and II Tumors

The morphologic and immunohistochemical profiles of gastric mucosa and of the tumor were assessed in Siewert type I, type II, and gastric antrum adenocarcinomas. Sixty-two patients, prospectively operated upon, were included in the study: 37 type II, 15 type I, and 10 antrum adenocarcinoma. Samples of the tumor, the surrounding area, and the gastric corpus and antrum were analyzed histologically, and immunostained for cytokeratins (CK)7/20 (staining positive for cells labeled > or = 50%). Among the 37 type II adenocarcinomas were the following: (1) 13 of 37 (35%) had intestinal metaplasia (IM) in the stomach; (2) 24 of 37 (65%) did not show IM at any level; (3) 34 of 37 (92%) had Helicobacter pylori (HP) infection; (4) 13 of 37(35%) had CK7/20 expression of "Barrett's type" (CK7+/20-); 24 of 37 (65%) had a "no Barrett's type" profile (10 of 37 with CK7-/CK20+ and 14 of 37 with CK7+/CK20+); (5) 100% showed the same CK immunoprofile, both in IM and adenocarcinoma (measure of agreement k = 1, p = 0.000). Type I adenocarcinomas showed the following: (1) 87.5% CK Barrett's type, both in the tumor, and in the surrounding IM; (2) 100% gastric samples devoid of both IM and HP infection. Comparison between CK immunoprofiles in type I and type II tumors showed a difference within the two groups (p = 0.002). One hundred percent of antrum adenocarcinomas showed a no Barrett's type CK profile, both in the tumor and in the IM of the entire stomach. Data suggest that type II adenocarcinoma cannot be always considered a gastroesophageal reflux disease-related tumor; other pathogenetic pathways should be taken into consideration.

Isolation and characterization of the potential receptor for wheat germ agglutinin from human neutrophils

Neutrophils participate in host protection and central to this process is the regulation of oxidative mechanisms. We purified by affinity chromatography the receptor for the GlcNAc-specific WGA from CD14+ CD16+ cell lysates (WGAr). The receptor is a 141 kDa glycoprotein constituted by two subunits of 78 and 63 kDa. It is mainly composed of Ser, Asx, and Gly, and, in a minor proportion, His, Cys, and Pro. Its glycan portion contains GlcNAc, Gal, and Man; NeuAc and GalNAc were identified in a minor proportion. The amino acid sequence of the WGA receptor was predicted from tryptic peptides by MALDI-TOF, both subunits showed homology with cytokeratin type II (26 and 29% for the 78 and 63 kDa subunits, respectively); the 78 kDa subunit showed also homology with the human transferrin receptor (24%). Antibodies against WGAr induce higher oxidative burst than WGA, determined by NBT reduction; however, this effect was inhibited (p < 0.05) with GlcNAc suggesting that WGAr participates as mediator in signal transduction in neutrophils.

Hepatology highlights

Hepatology highlights

Secretory meningioma: immunohistochemical findings and evaluation of mast cell infiltration

Secretory meningiomas constitute a relatively rare subtype of meningiomas, accounting for only 1.1% at our institution, with a 6:1 predominance of female patients. This study aimed to obtain more information about the immunohistochemical characteristics of this histological entity, and to analyse the effects of histological factors such as the presence of mast cells on the radiological evidence of surrounding tumour oedema that frequently occurred in this subtype of meningioma. Fourteen cases of secretory meningioma were examined. Relevant clinical information was obtained from the patient files. Peritumoural oedema was determined either by CT or MRI scans and graded as small, moderate and severe. In order to perform the quantitative evaluation of mast cells in secretory meningiomas in a comparison with other meningiomas, 14 non-secretory meningiomas were randomly selected and used as a control group. The immunohistochemical staining of carcinoembryonic antigen was positive within the secretory droplets and the cells surrounding them in all cases. Ki 67 (MIB 1) proliferative index mean values were 2.4%, indicating low expression in all secretory meningiomas. Moreover, from our statistical analysis, there is no clear-cut pattern of various types of cytokeratins emerging in secretory meningiomas. The secretory meningiomas were characterized by a significantly increased number of mast cells as compared with non-secretory meningiomas of different grades. As the present clinical findings and laboratory results could not confirm a correlation between mast cell density and radiological evidence of oedema, further studies of mediators are warranted.

Proteomic analysis of aqueous humour from patients with acute corneal rejection

To compare the basic proteomic composition of aqueous humour (AH) from patients with corneal rejection (patients) with AH from patients with cataract (controls). Aqueous humour was analysed for total protein concentration using Bradford's method and for protein composition using two-dimensional (2D) gel electrophoresis. Image analysis was used to detect protein spots in 2D gels that were increased by more than factor 2 in patients as compared with controls. Increased spots were identified by immunoblotting and mass spectrometry. Aqueous humour from patients contained significantly higher total protein concentration than did AH from controls. A total of 31 spots were significantly increased in 2D gels from patients. The spots were derived from albumin, alpha1-antitrypsin, apolipoprotein J, cytokeratin type II, serin proteinase inhibitor and transthyretin. After correction of spot volumes by total protein concentrations, 10 spots derived from albumin, cytokeratin type II and alpha1-antitrypsin remained significantly increased. The proteomic composition of AH differed significantly between patients and controls. The identified proteins suggest that the changes in AH are due to at least three different mechanisms: breakdown of the aqueous-blood barrier, enzymatic degradation, and liberation of locally synthesized proteins.

Cytokeratin expression in primary epithelial cell culture from bovine conjunctiva

Aim of the present study is to extend our previous observations on a model of primary epithelial cell culture obtained from bovine conjunctiva, and analyse the maintenance of the conjunctival phenotype, relative to cytokeratin (CK) expression, through extended periods of cultivation under different conditions. Conjunctival epithelial cells were grown in transwell filters, and cultured either under liquid covered (LC), or air-interface (AI) conditions. The physiological state of the cells was monitored daily by measurement of the trans-epithelial electrical resistance (TEER). Analysis of cytokeratin expression was then carried out at different time points (up until 14 days), and compared to the original profile of the conjunctival tissue in order to assess deviations from the primitive phenotype. Immunodetection studies, carried out by both western immunoblot and immunofluorescence analyses, revealed constant expression of the pan-epithelial marker AE3 (recognizing basic type cytokeratins), confirming the epithelial nature of the culture. Other cytokeratins characteristic of non-keratinized stratified epithelia (CK4 and CK13) were absent in corneal tissue, while in conjunctival epithelial cells were more expressed under AI than under LC culture conditions. Expression of CK12, a specific marker of corneal tissue, revealed by the antibody AE5, was never observed in conjunctival epithelial cells. These results indicate that the conjunctival phenotype is conserved during extended periods of culturing, making this system a reliable substitute of conjunctival tissue for pharmaceutical analyses.

Prognostic and diagnostic significance of beta-catenin nuclear immunostaining in colorectal cancer.

In the present study, we investigated the prognostic and diagnostic significance of beta-catenin nuclear immunostaining in 60 specimens of normal colorectal tissue; 180 specimens of colorectal polyps, adenomas, and carcinomas; and 40 specimens from patients with the simultaneous occurrence of polyps, adenomas, and carcinomas. Additional specimens from 59 patients with colorectal carcinoma and 14 patients with adenoma who subsequently developed carcinoma were examined for possible survival study. Immunohistochemical staining showed that the occurrence of nuclear beta-catenin correlated with the sequential stages in colorectal carcinogenesis, in which positive staining was observed in 0% of normal tissues, 8% of polyps, 92% of adenomas, and 100% of carcinomas. High immunohistochemical scores in colorectal carcinoma were significantly associated with lymph node metastasis and poor survival. Adenomas associated with synchronous or metachronous carcinomas showed significantly higher levels of nuclear beta-catenin compared with adenomas without associated carcinomas. Nuclear translocation of beta-catenin was rare or absent in other types of cytokeratin 20 positive adenocarcinomas examined (99 cases). Thus, it was positive in only 7% of colonic mucinous adenocarcinomas, 3% of pancreatic adenocarcinomas, 8% of ovarian mucinous cystadenocarcinomas, and 0% of gastric adenocarcinomas. However, 100% of primary and metastatic colorectal adenocarcinomas were positive for nuclear staining for beta-catenin. Thus, nuclear staining for beta-catenin may serve as an additional parameter to help distinguish colorectal adenocarcinomas from adenocarcinomas of other tissue sites. Collectively, the present large-scale study has clearly addressed the clinical significance of beta-catenin nuclear translocation with respect to tumor progression, survival, and differential diagnosis.

Hepatology highlights

Hepatology highlights

Brush cells of rodent gallbladder and stomach epithelia express neurofilaments.

It has been suggested that brush cells (BCs), a distinct type of cell occurring in various epithelia of the respiratory and gastrointestinal tracts, may function as receptor cells. The major characteristics of BCs are a prominent brush border and an unusually highly ordered arrangement of cytoskeletal elements (F-actin, microtubules, and intermediate filaments). In this study we aimed to characterize the nature of the intermediate filaments in BCs by light and electron microscopic immunostaining. Gallbladder and stomach specimens from mice and rats, respectively, were fixed in various solutions, embedded either in paraffin or epoxy resin, and processed for immunodetection. Commercially available, well-characterized antibodies against neurofilaments, peripherin, and cytokeratin peptide 18 were used. The polyclonal antiserum cocktail to neurofilaments was applied as a supplement in a double-labeling procedure with anti-actin and anti-cytokeratin 18 antibodies. The results demonstrate that the BCs of both organs express two types of intermediate filaments, i.e., neurofilaments and cytokeratin 18 filaments, and that these have a compartmentalized distribution in the cytoplasm. BCs do not express peripherin. The immunodetection of intermediate filaments distinctive for mature neurons in BCs supports their putative receptor function. The co-expression of neurofilaments and cytokeratins is shown for the first time in healthy tissues.

Double immunohistochemical labeling technique applied to different types of cytokeratins in epithelial proliferations of the breast

The double labeling technique using peroxidase and alkaline phosphatase for immunohistochemistry is well known, but must be adapted according to the antibodies used, fixation, and technical conditions. The technique allows identification on one slide of two antigens that are localized in the same or different cells of the same lesion. The aim of this paper is to describe the adaptation of this technique to cytokeratins of normal mammary tissue and proliferative lesions of the breast.

Small adenocarcinomas of the esophagogastric junction: association with intestinal metaplasia and dysplasia.

Intestinal metaplasia in Barrett's esophagus predisposes to esophageal adenocarcinoma. Intestinal metaplasia of the cardia is a common finding in persons without cancer. Many adenocarcinomas of the esophagogastric junction are large enough to obliterate any underlying intestinal metaplasia. To estimate how often adenocarcinoma of the esophagogastric junction arises in intestinal metaplasia, we studied small adenocarcinomas of the esophagogastric junction. Resection patients had adenocarcinomas 2 cm or smaller, within 2 cm of the esophagogastric junction. Age- and sex-matched controls had resection for squamous carcinoma. Saved and new histological slides from the esophagogastric junction were examined, with additional stains. Intestinal metaplasia was found in 86% (19/22) of adenocarcinoma cases, versus 32% (7/22) of controls (p < 0.001). Intestinal metaplasia with high or low grade dysplasia was associated with 64% (14/22) of adenocarcinomas and with 5% (1/22) of controls (p < 0.001). Excluding four cases with long and three with short Barrett's esophagus, 80% (12/15) of adenocarcinomas had associated intestinal metaplasia, 53% (8/15) with dysplasia. Most adenocarcinoma cases had the incomplete type of intestinal metaplasia with a Barrett type cytokeratin 7/20 staining pattern. Helicobacter pylori were seen in one adenocarcinoma and five control cases. Most adenocarcinomas of the esophagogastic junction arise in the background of intestinal metaplasia, sometimes in an endoscopically visible Barrett's esophagus, more often in small areas of intestinal metaplasia of the cardia. In cases of adenocarcinoma, the intestinal metaplasia resembled that found in Barrett's esophagus, and was not associated with H. pylori.