Protein-losing enteropathy post-valvular surgery with severe tricuspid regurgitation in Subutex-related endocarditis.

We report a 25-year-old Malay man with Subutex-related endocarditis, complicated by protein-losing enteropathy from severe tricuspid regurgitation and congestive heart failure. The intestinal protein loss was reversed with surgical valvular intervention. This case highlights the importance of recognising the rare association between protein-losing enteropathy and congestive heart failure in the setting of endocarditis.

Ectopic enterogenous cyst.

Enterogenous cyst is a rare congenital lesion presumably of endodermal derivation. It is usually located in the medistinum, the abdominal cavity, skull or within the spinal canal. To our knowledge, it has not been reported in the subcutaneous tissue. We report the first case of ectopic (left scapular region) subcutaneous enterogenous cyst in a 46-year-old man, who presented with a lump over the left scapular region of several years' duration. Clinical diagnosis of lipoma was made. The final histological diagnosis was enterogenous cyst. Enterogenous cysts at ectopic locations should be kept in mind and studied further especially with respect to their development. A better understanding of the embryology, histopathology and genetics of ectopic enterogenous cyst is desired.

Inhibition of histone deacetylase 2 increases apoptosis and p21Cip1/WAF1 expression, independent of histone deacetylase 1.

Histone deacetylases (HDACs) 1 and 2 share a high degree of homology and coexist within the same protein complexes. Despite their close association, each possesses unique functions. We show that the upregulation of HDAC2 in colorectal cancer occurred early at the polyp stage, was more robust and occurred more frequently than HDAC1. Similarly, while the expression of HDACs1 and 2 were increased in cervical dysplasia and invasive carcinoma, HDAC2 expression showed a clear demarcation of high-intensity staining at the transition region of dysplasia compared to HDAC1. Upon HDAC2 knockdown, cells displayed an increased number of cellular extensions reminiscent of cell differentiation. There was also an increase in apoptosis, associated with increased p21Cip1/WAF1 expression that was independent of p53. These results suggest that HDACs, especially HDAC2, are important enzymes involved in the early events of carcinogenesis, making them candidate markers for tumor progression and targets for cancer therapy.

Expression of cell-cycle regulators p27 and cyclin E correlates with survival in gastric carcinoma patients.

BACKGROUND: Cell-cycle control is important in carcinogenesis and cancer progression. p27 and cyclin E are cell-cycle regulators, which control the G1-S phase transition. Recently, these two factors were found to be affected in many human cancers. The aim of the study was to examine the expression of p27 and cyclin E in gastric cancer and to evaluate their prognostic implication. MATERIALS AND METHODS: Paraffin blocks of 56 samples of advanced gastric cancer, 15 samples of early gastric cancer, and 17 samples of normal gastric mucosa were studied. Expression of p27 and cyclin E was analyzed by immunohistochemistry. The relationship between the expression and clinicopathological data was examined. RESULTS: Expression of p27 was reduced in 89% of advanced cancer samples, 44% of early cancer samples, and 12% of normal mucosa samples (P<0.0001). Among the cancers, reduced expression of p27 was associated with a large tumor size, increased cancer invasion, nodal metastases, and the presence of residual tumor after operation. No significant difference in cyclin E expression was found. Kaplan-Meier plots of survival showed tumors with low p27 were associated with poorer survival than those with high p27 expression (RR, 5.3; CI = 1.6-17.4; P = 0.005). Tumors with low p27 and high cyclin E expression were associated with the highest mortality expression (RR, 9.8; CI = 1.2-80; P = 0.03). CONCLUSIONS: Gastric cancer with low expression of p27 is associated with aggressive characteristics and a poorer outcome.

Caroli's disease associated with a gastric diverticulum.

Caroli's disease or communicating ectasia of the intrahepatic biliary tree is a rare disease with unknown aetiology. The coexistence of this along with the uncommon condition of a gastric diverticulum has never been reported before. A deficiency in the fibromuscular matrix of both the bile ducts and the gastric wall may explain why these two pathologies may coexist in a single patient.

An immunohistochemical study of p53 protein in cervical intraepithelial neoplasia and squamous cell carcinoma.

p53 mutations are known to occur frequently in human cancers where they are considered to be an important event in the stepwise progression towards malignant transformation. It is therefore interesting to compare p53 expression in the uterine cervix for non-neoplastic/metaplastic squamous epithelium, cervical intraepithelial neoplasia (CIN) and invasive squamous cell carcinoma. One hundred and nineteen biopsied and resected specimens of the uterine cervix were stained with an anti-human p53 protein monoclonal antibody by the streptavidin-biotin immunoperoxidase method. Histologically these could be categorized into non-neoplastic/dysplastic conditions, including condyloma (34 cases), CIN 1-3 (66 cases) and invasive squamous cell carcinoma (19 cases). Fifty eight per cent (11/19) of the invasive squamous cell carcinomas and 11% (7/66) of the CIN stained positively for p53. Except for 3 cases of invasive squamous cell carcinoma, there was only sporadic intranuclear staining of less than 5% of the cells. No staining was observed in all non-neoplastic/metaplastic squamous epithelial cells. The pattern of p53 staining is significantly different for all 3 categories. However it is undetermined as to whether the positive immunoperoxidase staining is a direct consequence of p53 gene mutation or otherwise.

p53 expression in hepatocellular carcinoma in a population in Singapore with endemic hepatitis B virus infection.

AIMS: To study the expression and clinical significance (if any) of p53 protein in hepatocellular carcinomas (HCC) arising in a population with endemic hepatitis B virus (HBV) infection. METHODS: Immunohistochemical staining was performed on formalin fixed, paraffin was embedded histological sections of 46 HCC cases using an antihuman p53 monoclonal antibody; serial sections were also stained for hepatitis B surface antigen (HBsAg), hepatitis B core antigen (HBcAg) and alpha fetoprotein (AFP). Nuclear p53 staining was assessed according to intensity (absent, weak or strong) and extent (< 5%, 6-25%, 26-50%, and > 50%) of positive cells. Tissue HBsAg, HBcAg and AFP were recorded as absent or present. RESULTS: The p53 protein was expressed in 35% (16 of 46) of HCCs; the positive rate in grade III/IV tumours (13 of 31; 42%) was higher than in grade I/II tumours (three of 15; 20%) but this was not statistically significant. HBsAg positive tumours showed almost the same proportion of p53 staining (11 of 29; 38%) as HBsAg negative ones (five of 17; 29%). CONCLUSIONS: The p53 protein was expressed in 35% of HCC cases. There was no statistically significant correlation between HBV infection and p53 protein expression. Similarly, there was no definite correlation between p53 positivity and tumour size, histological grade or vascular invasion.

Expression of the proliferating cell nuclear antigen in cervical neoplasia.

The expression of the proliferating cell nuclear antigen (PCNA) was examined to determine the proliferative activity of the cells in nonneoplastic and neoplastic lesions of the uterine ectocervix. Formalin-fixed, paraffin-embedded tissue sections of uterine cervix including normal, metaplasia, condyloma, intraepithelial neoplasia and invasive squamous cell carcinoma were stained immunohistochemically using monoclonal antibody to PCNA. The percentage of PCNA-positive cells was significantly higher in premalignant and malignant lesions of the uterine cervix than in nonneoplastic lesions. Furthermore, the growth fraction of tumor cells as detected by PCNA was increased in accordance with the progression of neoplasia. The results of this study suggest that the cell proliferation index as detected immunohistochemically using PCNA may be a useful adjunct to histological diagnosis of various grades of dysplasia.

An immunohistochemical study of p53 protein in gallbladder and extrahepatic bile duct/ampullary carcinomas.

BACKGROUND: p53 mutations are known to occur frequently in human cancers, including gallbladder carcinoma. However, there has been no study of p53 expression in extrahepatic bile duct/ampullary carcinoma. Furthermore, gallbladder carcinoma is associated with cholelithiasis, whereas no such association is known for extrahepatic bile duct carcinoma, suggesting that they could arise from different pathogenetic mechanisms. METHODS: Twenty-four gallbladder carcinomas and 35 extrahepatic bile duct/ampullary carcinomas were stained with an anti-human p53 protein monoclonal antibody by the streptavidin-biotin immunoperoxidase method. Both the extent and intensity of p53 protein staining were noted. RESULTS: Ninety-two percent of the gallbladder carcinomas stained for p53 protein compared with only 66% of the extrahepatic bile duct/ampullary carcinomas. The statistical significance was maintained even when the comparison was restricted to strong p53 staining in moderately to poorly differentiated adenocarcinomas (P < 0.05). Of the gallbladder carcinomas, poorly differentiated adenocarcinomas stained more strongly than well to moderately differentiated adenocarcinomas; the converse was true for extrahepatic bile duct/ampullary adenocarcinomas. CONCLUSION: The majority of gallbladder and extrahepatic bile duct/ampullary carcinomas stain for p53 protein. The incidence and pattern of staining is different, however, and supports the contention that these could be different tumors with differing etiologies and pathogenetic mechanisms.

Diagnosis of left atrial myxoma following systemic embolism.

Cardiac myxomas are rare and noted for their varied clinical manifestations. Consequently, the diagnosis is often unsuspected until the symptoms and signs become advanced and obvious, or when the diagnosis is made fortuitously during echocardiography. This report illustrates a case in point in which the diagnosis was made on transthoracic echocardiography and amplified using transesophageal echocardiography.

Adenomyoepithelioma of the breast. Report of a case with fine needle aspiration cytology and histologic, immunohistochemical and ultrastructural correlation.

A case of adenomyoepithelioma of the breast was studied by cytology, histology, immunohistochemistry and electron microscopy. Aspiration cytology of the tumor showed sheets and tubular-type clusters of cohesive, regular polygonal cells with abundant, fairly well preserved, pale, granular to finely vacuolated, clear cytoplasma and a low nuclear/cytoplasmic ratio. The nuclei were small, round and monotonous, with dispersed chromatin and small or inconspicuous nucleoli. Acinus formation was striking: an occasional gland showed a suggestion of an inner layer of cells with denser cytoplasm surrounded by an outer mantle of paler cells. The histologic, immunohistochemical and ultrastructural findings confirmed the two cell populations, constituting an inner epithelial and outer myoepithelial component, both participating in the neoplastic process. The differential diagnoses of various breast lesions with somewhat similar cytologic features are discussed.

Clinical importance of p53 protein in gall bladder carcinoma and its precursor lesions.

AIMS: To study the expression and importance (if any) of p53 protein in gall bladder carcinoma and its precursor lesions. METHODS: Immunohistochemical staining was performed on formalin fixed, paraffin wax embedded histological sections with an anti-human p53 monoclonal antibody (DO-7; Dako Corporation M7001) (24 carcinomas, one adenocarcinoma in situ, six dysplasias, three adenomas and four cases of chronic cholecystitis). Invasive, in situ, and dysplastic areas as well as normal-looking epithelium were sought. Nuclear staining was assessed according to intensity and extent of positive cells. Both variables were graded on a scale of 1-3 and aggregate p53 scores were obtained (range: 0, 2-6). Only p53 scores of > or = 3 were regarded as significant. RESULTS: Clinically important amounts of p53 were expressed in 92% of invasive carcinomas, 86% of carcinoma in situ, and 28% of dysplastic areas. None of the adenomas contained clinically important amounts of p53. Normal epithelium, present in all the cases, did not express p53 except in one case of moderately differentiated adenocarcinoma (p53 score 3). In general, there was no difference in the prevalence of p53 protein expression between dysplasias associated with, and those unassociated with invasive disease. There was a tendency for higher grade carcinomas to express more p53 protein. CONCLUSIONS: The distribution of p53 protein in invasive carcinomas and the adjacent dysplastic and preinvasive lesions suggests that it is more commonly expressed than previously thought. The fact that p53 protein is also expressed in cases of dysplasia and carcinoma in situ unassociated with invasive malignancy lends further support to the contention that p53 gene mutations may have a role in the pathogenesis of gall bladder cancer. Expression of p53 protein may possibly be an indication of likely disease progression from dysplasia, to carcinoma in situ, to invasive disease.

HLA-DR antigen expression in colonic adenomas and adenocarcinomas.

Previous studies have shown that malignant transformation is sometimes associated with the aberrant expression of HLA class II antigens. The functional significance of such aberrant expression is not known. Since HLA-DR antigen is expressed in normal colonic mucosa, it would be interesting to see if malignant transformation could result in the aberrant suppression of this antigen. Sixteen colonic adenocarcinomas, 29 colonic adenomatous polyps and 23 samples of normal colonic mucosa, including 9 cases of colonic mucosa adjacent to carcinoma, were stained immunohistochemically for HLA-DR antigen. The intensity and distribution of the antigen staining in the cytoplasm and luminal surface of the epithelial elements were analysed semiquantitatively. The lymphoplasmacytic infiltrate in the lamina propria was also evaluated. Cytoplasmic HLA-DR antigen expression was found to be significantly diminished in moderately and poorly differentiated adenocarcinomas but not in adenomas or well-differentiated adenocarcinomas. This suggests that the change in HLA-DR expression is not intrinsic to the neoplastic process but may merely be due to the fact that malignant cells, as they become less differentiated, tend to show alterations in their antigenic phenotype.

The expression of HLA-DR antigen in cervical neoplasia.

The purpose of this study was to evaluate the relationship between cervical neoplasia and HLA-DR antigen (class II antigen) expression. Seventy-seven formaldehyde-fixed uterine specimens comprising morphologically normal cervix (12), chronic cervicitis (10), cervical intraepithelial neoplasia (CIN) of various grades (42), and invasive squamous cell carcinoma (13) were studied for the degree and type of inflammation, and immunohistochemically for the HLA-DR antigen expression in the epithelium. The nonneoplastic ectocervical squamous epithelium was consistently negative for HLA-DR antigen, even in sections showing significant lymphoplasmacytic infiltration. We found HLA-DR antigen positivity in endocervical glandular epithelium, immature metaplastic squamous epithelium, CIN, and invasive carcinoma. In cases of CIN, the aberrant expression of the antigen generally corresponded to the level of dysplasia. Specific cells exhibiting koilocytic change were negative. All the cases of squamous cell carcinoma expressed the antigen, albeit variable in intensity and distribution. These findings suggest that aberrant HLA-DR antigen expression in the uterine ectocervix may be a consequence of dysplastic changes of the squamous epithelium that is maintained even after malignant transformation. On the other hand, HLA-DR positivity in immature metaplastic epithelium is probably a mere reflection of the fact that normal endocervical glandular epithelium can express the antigen.

Expression of HLA-DR antigen in different histological types of gastric polyp.

AIMS: To study the expression of HLA-DR antigen in the different histological types of gastric polyps. METHODS: Ninety five cases of gastric polyps were histologically classified and examined for the presence of Helicobacter pylori, and for degree and type of inflammation. Further sections were stained immunohistochemically for HLA-DR antigen expression in the epithelium using a monoclonal antibody that was reactive to formalin-fixed paraffin wax embedded tissue. RESULTS: HLA-DR antigen was expressed in all of the inflammatory polyps studied (20/20), and in most hyperplastic (12/16) and adenomatous (4/6) polyps. Only a few fundic gland polyps (8/51) stained positively for HLA-DR antigen. Gastric polyps seem to have a greater tendency to express HLA-DR antigens than non-polypoid gastric mucosa, even after considering the factors that may affect HLA-DR antigen expression, such as inflammation and the presence of H pylori. CONCLUSIONS: Growth disturbances/polyp formation may be associated with increased HLA-DR antigen expression.

Bilateral carcinoid tumor of the breast. Report of a case with diagnosis by fine needle aspiration cytology.

A case of bilateral carcinoid tumors of the breast was studied by cytology, histology, immunohistochemistry and electron microscopy. The preoperative aspiration cytologic findings strongly suggested a carcinoid tumor of the breast. The differential diagnosis with fine needle aspiration cytology of other breast lesions, the bilaterality of the condition and terminology are discussed.

The histological and immunohistochemical evidence of squamous metaplasia from the myoepithelial cells in the breast.

Squamous metaplasia in the breast is well documented. However, the putative cell of origin for the squamous epithelium is not clear. This paper describes a case of fibroadenoma of the breast with myoepithelial hyperplasia and squamous metaplasia. The histological finding of transition between myoepithelial cells and squamous cells and the immunohistochemical expressions of actin and S-100 in the metaplastic squamous cells support the myoepithelial origin of squamous epithelium in the breast.

Spindle cell carcinoma of the breast.

A case of spindle cell carcinoma of the breast in association with myoepithelial cell hyperplasia is presented. Immunocytochemistry demonstrated labelling of tumour cells for cytokeratin, vimentin and S-100 protein. Electronmicroscopy showed desmosomes and bundles of tonofilaments as well as fine filaments in the cytoplasm. The findings in the present case point to the metaplastic spindle cell nature of squamous carcinoma of the breast. The possible role of myoepithelial cells in the origin of the spindle cell component is discussed.