Cytokeratin expression in cauda equina paragangliomas.
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Carcinoid Tumor↗
Biomedical subjects
R Chetty
Publications and source records attributed to R Chetty.
Allelic imbalance and microsatellite instability in chromosomes 2p, 3p, 5q, and 18q in esophageal squamous carcinoma in patients from South Africa.
Microsatellite polymerase chain reaction (PCR) and fluorescent DNA technology was used to assess allelic imbalance (AI) or loss of heterozygosity (LOH) and microsatellite instability (MSI) in chromosomes 2p, 3p, 5q, and 18q in esophagectomy specimens from 39 patients who had squamous carcinoma and who lived in a high-incidence geographic location in South Africa. The squamous carcinomas were graded by conventional light microscopy and staged using the tumor-node-metastasis (TNM)-Union Internationale Contre Le Cancer (UICC) criteria. The DNA was isolated using proteinase K digestion and standard phenol-chloroform extraction procedure. Microsatellite PCR was performed using fluorescent, CY5-labeled primers for the following markers: D2S123 (2p), D3S659 (3p), D3S1255 (3p), D5S346 (5q), DCC (18q), D18S34 (18q), and D18S58 (18q). These markers were chosen because they are the most frequently used and most informative markers for these particular gene loci. Results were analyzed using software attached to an automated DNA sequencer. Molecular changes obtained were correlated with clinicopathologic parameters. Molecular analysis did not correlate with clinicopathologic features, such as tumor grade, stage, or lymph node status. No correlation with patient outcome was seen, though only limited follow-ups were obtained. Rates of MSI and LOH on 3p and 18q in these specimens are similar to the range seen in studies from other geographic areas. However, a striking point of departure is the high LOH (30% of informative cases) seen on 2p.
Adult↗
Vasculitis-induced membranous fat necrosis.
Membranous fat necrosis (MFN) a distinct degenerative process of adipose tissue, is characterised by the presence of membranocystic lesions (MCLs) superimposed on a background of typical traumatic-type fat necrosis. MCLs are cysts, of varying size and shape, that are lined by an eosinophilic, crenulated membrane, having the staining properties of ceroid. Although MFN has been documented in varying systemic adipose tissue sites and in tumours, the pathogenesis of this pathological curiosity is unknown. To date, an ischemic basis for MFN has been the most proximate, and atherosclerosis and venous insufficiency, due to large and medium vessel disease, have been the most popular underlying clinical disorders. Although systemic vasculitis has been quoted as the underlying ischemic disorder in some patients, vasculitis has not been commented on nor demonstrated in tissue sections in association with MFN. In,reporting vasculitis-induced MFN, we document the occurrence of MFN in association with uncommon causes of vasculitis, namely: 1) Granulomatous vasculitis in a post-herpetic zosteriform scar; 2) Cytomegalovirus-induced vasculitis in the clinical setting of systemic lupus erythematosus; and 3) Lymphocytic vasculitis in a tetanus toxoid immunization site reaction.
Adolescent↗
Coexistent gastric MALT lymphoma and Kaposi sarcoma in an HIV positive patient.
A 47 year old HIV positive male presented with haematemesis and epigastric pain. A gastrectomy was performed for intractable bleeding. The cause of the haematemesis proved to be a Kaposi sarcoma of the stomach which had resulted in mucosal ulceration. Several other smaller foci of Kaposi sarcoma were also present. Coexistent with the Kaposi sarcoma was a dense lymphoid infiltrate with lymphoid follicles and reactive germinal centres. Centrocyte-like cells caused marked effacement and destruction of gastric glands with the formation of lymphoepithelial lesions, typical of a MALT lymphoma. These cells were of B cell lineage and some expressed the HIV antigen, p24. Follicular dendritic cells and macrophages within germinal centres were also p24 positive. Immunohistochemistry and in situ hybridisation did not detect Epstein-Barr virus. Although Helicobacter pylori was not identified by light microscopy in the sections sampled, this does not preclude its possible role, with other cofactors such as HIV, in the causation of the MALT lymphoma.
Gastrectomy↗
DNA repair gene status in oesophageal cancer.
DNA repair genes and microsatellite instability (MSI) are relatively recently described molecular events that have been associated particularly with colorectal cancers in the setting of hereditary non-polyposis colorectal cancer or the Lynch syndromes. Several other gastrointestinal (and other) malignancies have been analysed for abnormalities in DNA repair genes and MSI. Dietary and environmental factors have been implicated strongly in the aetiology of oesophageal cancer. However, the effect of this on the genetic profile, especially the DNA repair system and resultant MSI, is largely unknown. The purpose of this review is to provide a brief background of the dietary and environmental factors in oesophageal carcinogenesis and to discuss the role of the repair genes and MSI in the molecular pathogenesis of this malignancy. Several studies indicate that MSI (range, 3-40%) and loss of heterozygosity (LOH) (range, 3-64%) in the DNA repair genes are uncommon in carcinogenesis of the oesophagus. Most data are at the lower end of the ranges and this, together with the lack of uniform criteria for the assessment of MSI, accounts for the higher figures obtained in some studies. The rates of detection of MSI do not approach that of other gastrointestinal malignancies, such as gastric (up to 23%) and colorectal (up to 31%) carcinomas.
DNA Repair↗
Gastro-intestinal Kaposi's sarcoma, with special reference to the appendix.
Kaposi's sarcoma (KS) of the gastro-intestinal tract is a common disease in the AIDS setting, although it is often asymptomatic. In this paper we wish to highlight the occurrence of gastro-intestinal KS with appendiceal involvement. Two of the patients presented with features of acute appendicitis, and KS of the appendix was not suspected at the time of surgery. In the remaining patient KS of the appendix was part of generalised gastro-intestinal involvement. It is important to remember that KS can cause appendicitis by producing a submucosal nodule that abuts into the lumen and thereby causes obstruction. KS of the gastro-intestinal tract may therefore masquerade as 'simple' appendicitis, or indeed remain asymptomatic.
Acquired Immunodeficiency Syndrome↗
Heterotopic pancreas--an unusual cause of cholecystitis.
A 47-year-old woman presented with signs and symptoms of acute cholecystitis. A routine cholecystectomy was performed. No gallstones were present. On histological examination of the gallbladder, a nodule impinging on the lumen was present in the region of the cystic duct. This nodule was composed of mature, uninflamed exocrine and endocrine pancreatic tissue. In the absence of gallstones, the heterotopic pancreas was the cause of obstruction, with subsequent cholecystitis.
Acute Disease↗
Persistent and chronic lung disease in HIV-1 infected and uninfected African children.
OBJECTIVE: The causes of persistent lung disease (PLD) and chronic lung disease (CLD) are unknown in HIV-infected children in developing countries. We describe the causes and course of PLD and CLD in HIV-infected and uninfected children. METHOD: Of 194 children with lung disease persisting for at least 1 month who were seen at the paediatric respiratory clinic over a 2-year period, 42 underwent invasive investigations after failed initial management over 3 months. PLD was defined as the presence of clinical and radiological features of lung disease for more than 1 month, and CLD as these features for more than 3 months. RESULTS: One hundred and thirty-eight (71%) of the 194 children with PLD were HIV-infected, 52 (27%) were not infected and four (2%) were of undetermined HIV status. Forty-eight per cent of the HIV-infected children and 52% of the HIV-uninfected children responded to initial treatment over 3 months; the presumptive diagnoses in these were tuberculosis, interstitial pneumonitis, bronchiectasis and post-ventilation lung syndrome. Of the 28 HIV-infected children with CLD who underwent invasive investigations 16 (57%) had lymphoid interstitial pneumonitis, eight (29%) had tuberculosis and four (14%) had non-specific interstitial pneumonitis. Of the 14 HIV-uninfected children with CLD who had invasive testing there were four cases (29%) each of tuberculosis and interstitial pneumonitis, three (22%) cases of bronchiectasis and one case of each of extrinsic allergic alveolitis, crytogenic fibrosing alveolitis and non-Hodgkin's lymphoma. CONCLUSION: This is the first set of data on the causes of CLD in HIV-infected children in a developing country. Every effort should be made to identify the infectious agent, whether M. tuberculosis or a secondary bacterial infection in LIP, in order to treat most appropriately these children with lung disease.
Child↗
The application of microsatellites in molecular pathology.
Present within the genome are large numbers of seemingly unimportant DNA segments arranged in repetitive units. Furthermore, these stretches of DNA contain variations or polymorphisms that are characteristic for an individual and results in a unique DNA fingerprint. Approximately 30% of the DNA repeat sequences are arranged as short tandem repeat sequences, which are called microsatellites. Microsatellites may consist of 1, 2 or 3 nucleotides; dinucleotides being the commonest. Microsatellites are characterised by being: stably inherited and hence highly conserved from one generation to the next, and unique to an individual and the same in different cells from the same individual. As a result of the above features, microsatellites can be used for personal identification, population genetic analysis and construction of evolutionary trees. In addition, they are located in several important gene loci and this allows microsatellites to be used as markers of disease and to provide information about individual gene status, especially in tumors. This can be accomplished by assessing allelic imbalance or loss of heterozygosity of a particular gene by analysing microsatellites located at specific loci in the gene. Recently, mutations within microsatellites have been described as a result of defective DNA repair mechanisms, resulting in the phenomenon of microsatellite instability. This has been implicated in the aetiopathogenesis of several hereditary and non-hereditary conditions. There are several ways of analysing microsatellites, the popular using radioactively-labelled primers and autoradiography. This method has several drawbacks, especially the use of radioactivity and interpretative/technical problems. The use of fluorescently-labelled primers, automated DNA sequencing coupled with a computer software package obviates these problems. This technique has the added advantage of analysing several microsatellites in large numbers of cases, simultaneously. Thus, microsatellite analysis has become an important investigative tool for the molecular biologist and has provided new information in many diseases.
Autoradiography↗
Retinoblastoma and p53 protein expression in sporadic colorectal cancers.
AIMS: To ascertain if a relationship between retinoblastoma (pRb) and p53 proteins exists in sporadic colorectal carcinomas. METHODS: Fifty consecutive colectomy specimens for colorectal cancer in patients over the age of 50 and with no family history of cancers in the bowel were examined for immunoexpression of pRb and p53 proteins. These findings were then related to clinicopathological findings. Commercially available monoclonal antibodies to pRb and p53 were used on formalin-fixed, paraffin-embedded tissue. RESULTS: The most intense pRb immunoexpression was detected in well-differentiated, low-stage cancers. On the other hand, p53 expression was most intense in poorly differentiated, advanced-stage carcinomas. No statistically significant associations were noted with immunoexpression and age, gender or site of lesion. CONCLUSIONS: This study indicates that there is an inverse relationship between pRb and p53 protein expression in a proportion of sporadic colorectal cancers. Twelve tumours which showed low levels of pRb showed high levels of p53 protein. Similarly, seven tumours with high pRb levels displayed low p53 expression. In terms of immunohistochemical profile, p53-high/pRb-low tumours tended to be poorly differentiated and have advanced stage cancer.
Aged↗
p53 protein expression in nephroblastomas: a predictor of poor prognosis.
Alteration of the tumour-suppressor gene p53 is the commonest genetic change encountered in human malignant tumours. A study was undertaken to ascertain the prognostic value of p53 immunoexpression in nephroblastomas. A series of 93 consecutive cases was analysed. Archival formalin-fixed, paraffin wax-embedded tissue sections were stained with monoclonal anti-p53 antibody (DO-7, Dako) using a peroxidase-labelled streptavidin biotin kit. Five of seven tumours (71.4%) with unfavourable histology, but only 3 of 86 favourable histology tumours, showed 'high' p53 immunoexpression (P < 0.001). p53 expression in unfavourable histology tumours was present in both anaplastic and non-anaplastic components. Moreover, there was uniform staining of blastema, epithelium and stroma in unfavourable histology tumours. No statistical difference in p53 expression was found between patients who had received and those who had not received preoperative chemotherapy (P = 0.678). Similarly, no statistical difference was found in the groups of patients who were disease free, who had residual/recurrent disease or who had died (P = 0.238). The mean survival period for patients with tumours that had 'low' and 'high' expressions was 24.8 months and 12.6 months respectively (P = 0.0003). In conclusion, p53 immunoexpression in nephroblastomas was found to be an important determinant of poor prognosis as it identifies those patients with a shorter survival period and also those with unfavourable histology tumours. It may also be of practical value to the practising pathologist by identifying those tumours that require careful assessment for the presence of anaplasia.
Adolescent↗
Spindle epithelial tumour with thymus-like element (SETTLE): the predominantly monophasic variant.
AIMS: To describe two cases of spindle epithelial tumour with thymus-like element (SETTLE) which are composed predominantly of spindle cells. In addition, to highlight some unusual histological features in SETTLE and discuss its separation from histological mimics. METHODS AND RESULTS: The thyroid masses were in a 4-year-old boy and a 25-year-old male. Both patients were euthyroid and were well except for thyromegaly. The specimens were formalin fixed, and immunohistochemistry was performed on this material using a panel of antibodies following microwave antigen retrieval. Morphologically, the dominant pattern was of sheets of spindle cells arranged in several patterns. There was mild pleomorphism and occasional mitoses. There were very small foci of squamous epithelium and occasional ductular structures. The stroma was composed of fibrous tissue and isolated areas of calcification were noted. The spindle cells showed strong and diffuse immunoreactivity with AE1/3, CAM5.2 and vimentin. CONCLUSION: We describe two cases of SETTLE that are composed mainly of spindle cells and only a very focal ductular component. In addition, calcification was noted within the stroma in one of the cases. These predominantly spindle examples of SETTLE must be separated from synovial sarcoma, which is a more mitotically active, aggressive tumour displaying only patchy immunopositivity with epithelial markers.
Adult↗
HIV-associated lymphoepithelial cysts and lesions: morphological and immunohistochemical study of the lymphoid cells.
AIMS: To determine the morphology, immunophenotype and bcl-2 protein status of intraepithelial lymphocytes in HIV-positive lymphoepithelial lesions. METHODS AND RESULTS: Seventeen cases (from adults and children) of HIV-associated parotid and lung lymphoid lesions were examined. In addition, three lymphoepithelial cysts from HIV-negative patients were studied in parallel. Immunohistochemistry was performed on paraffin embedded tissue with the following antibodies: CD20, CD79a, CD3, CD4, CD8, bcl-2, CAM5.2, AE1/3, MIB1, kappa/lambda light chains and EBV-LMP-1. Heavy chain rearrangement was sought by polymerase chain reaction (PCR) in four of the cases. The lymphocytes participating in lymphoepithelial lesions of HIV-positive patients had the morphology of centrocyte-like cells with occasional cells resembling centroblasts. The majority of these cells were of B-cell lineage, but occasional intraepithelial T-cells (CD8 positive, CD4 negative) were also present. T-cells also formed a significant component of the infiltrative lymphoid cells outside the lymphoepithelial lesions. These were mainly CD8 positive, but very occasional CD4-positive T-cells were also noted. None of the cases showed light chain restriction and the four cases did not demonstrate heavy chain rearrangement by molecular biology. The interesting finding was the absence of bcl-2 expression by the intraepithelial lymphocytes. In contrast, the intraepithelial lymphocytes seen in the non-HIV setting were strongly bcl-2 positive. The majority of these were B-cells, and very occasional CD8 and CD4 positive T-cells formed the intraepithelial population. CONCLUSION: It is postulated that this finding is due to the HIV causing down-regulation of bcl-2 protein.
Adolescent↗
Cytokeratin expression in adrenal phaeochromocytomas and extra-adrenal paragangliomas.
AIM: To examine whether adrenal phaeochromocytomas and extra-adrenal paragangliomas are immunoreactive for commercially available and routinely used cytokeratin antibodies. METHODS: 18 extra-adrenal paragangliomas and seven adrenal phaeochromocytomas were stained with CAM 5.2, AE1/3, and 34 beta E12 following microwave antigen retrieval of formalin fixed tissue. RESULTS: A single case from the cauda equina was positive for both CAM 5.2 and AE1/3. In addition, two other cases--an intravagal and an orbital paraganglioma--also showed strong immunopositivity with CAM 5.2 and AE1/3. All phaeochromocytomas were negative with all epithelial markers. CONCLUSIONS: Cauda equina paragangliomas are known to stain with cytokeratins; however, occasional paragangliomas from other sites may also be immunoreactive with cytokeratins. If the results of immunohistochemistry are not interpreted in the clinical and morphological context, the failure to recognise that extra-adrenal paragangliomas may on occasion react with anticytokeratin antibodies may lead to their being confused with metastatic carcinomas.
Adolescent↗
Cyclin D1 and human neoplasia.
Neoplasia is characterised by abnormal regulation of the cell cycle. Cyclin D1 is a protein derived from the PRAD1, CCND1 or bcl-1 gene on chromosome 11q13, which is involved in both normal regulation of the cell cycle and neoplasia. In the G1 (resting) phase of the cell cycle, cyclin D1 together with its cyclin dependent kinase (cdk) partner, is responsible for transition to the S (DNA synthesis) phase by phosphorylating the product of the retinoblastoma gene (pRB), which then releases transcription factors important in the initiation of DNA replication. Amplification of the CCND1 gene or overexpression of the cyclin D1 protein releases a cell from its normal controls and causes transformation to a malignant phenotype. Analysis of these changes provides important diagnostic information in mantle cell (and related) lymphomas, and is of prognostic value in many cancers. Knowledge of cyclin D1's role in malignancy at the various sites, provides a basis on which future treatment directed against this molecule can proceed.
Biomarkers, Tumor↗
Allelic imbalance and microsatellite instability of the DCC gene in colorectal cancer in patients under the age of 35 using fluorescent DNA technology.
AIM: To assess allelic imbalance and microsatellite instability in the region of the "deleted in colorectal cancer" (DCC) gene on chromosome 18q using fluorescent DNA technology in colorectal cancer in patients under the age of 35. METHODS: Thirty two cases of colorectal cancer in patients under the age of 35 and with no family history of colon cancer were retrieved. DNA was extracted by standard methods, polymerase chain reaction (PCR) was performed using Cy5 labelled primers to microsatellite markers (D18S21, D18S34, and D18S58) in the DCC gene. The results were analysed using software attached to an automated DNA sequencer. RESULTS: The patients ranged in age from 17 to 35 years. Nineteen were women, all had left sided tumours (tumours distal to the splenic flexure). Twenty eight cases were either stage C or D (using the Astler Coller system). The informativity of the three markers were as follows: D18S21, 25 of 32 (78.1%); D18S34, 18 of 32 (56.25%); D18S58, 24 of 32 (75%). Allelic imbalance for the markers, after excluding homozygous and microsatellite instability cases, was: D18S21, 31.8%; D18S34, 11.7%; and D18S58, 0%. Nine cases showed allelic imbalance for both D18S21 and D18S34, yielding a combined allelic imbalance frequency of 39.1%. Ten cases showed microsatellite instability in at least one marker, with microsatellite instability seen most commonly for D18S58. Three cases showed microsatellite instability for all three markers. CONCLUSIONS: Approximately 39% of cases showed allelic imbalance for D18S21 and D18S34 markers, while microsatellite instability was found in 31.25% of cases. This figure is higher than that encountered in sporadic colorectal cancer over the age of 50, suggesting a role for the DNA repair genes in the pathogenesis of these cancers occurring under the age of 35.
Adolescent↗
Post-transplant lymphoproliferative disorders.
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Humans↗
Focal nodular hyperplasia of the liver coexisting with an adrenal pseudocyst.
A case of focal nodular hyperplasia (FNH) of the liver and an adrenal pseudocyst coexisting in the same patient is presented. The presentation was due to the large adrenal pseudocyst, which caused abdominal pain and swelling. At operation, the FNH was noted as an incidental finding. The aetiopathogenesis of both these lesions is thought to be the result of vascular malformation. FNH is associated with several other vascular malformations and lesions, and the association with an adrenal pseudocyst extends this concept. It also lends support to the theory that vascular abnormalities are important in the causation of these lesions.
Adrenal Gland Diseases↗