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R Chetty

Publications and source records attributed to R Chetty.

At least 91 records · Page 5Linked to original sources
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

MALT lymphoma.

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Child↗
PubMed1997

TAL-1 protein expression in vascular lesions.

The distribution of TAL-1 protein, an important vascular promoter in mice, has been examined immunohistochemically in a range of human vascular lesions and normal tissues. Formalin-fixed, paraffin-embedded vascular lesions including granulation tissue, haemangiomas, Kaposi's sarcomas, spindle cell haemangioendotheliomas, and angiosarcomas, were examined using a monoclonal antibody to recombinant TAL-1. Endothelial cells in all lesions gave positive immunostaining of variable intensity. Granulation tissue and spindle cell areas of the vascular tumours gave the strongest staining (nuclear and cytoplasmic). The better-differentiated endothelial cells within the tumours and resident well-formed vessels were less positive and some cells were in fact negative. The malignant endothelial cells in angiosarcomas showed less intense positive staining than KS cells. This study has shown TAL-1 protein expression in a range of reactive, benign, and malignant vascular lesions. Protein expression appears to be stronger in the spindle cell areas, perhaps reflecting greater expression in less-differentiated endothelial cells.

Adult↗
PubMed1997

Retinoblastoma protein and Epstein-Barr virus (EBV) expression in South African Hodgkin's disease.

The aim of this study was to explore the expression of retinoblastoma protein and EBV status in a cohort of cases of Hodgkin's disease from South Africa. Seventy one cases of Hodgkin's disease were accessed over a 6-year period and were classified according to the Rye Classification. Relevant sections were stained with commercially available antibodies to retinoblastoma protein (pRb) and EBV-LMP-1. In addition, in situ hybridization for EBERs was also performed. The results of this study show that 43 of 71 cases expressed EBV by both immunohistochemistry and in situ hybridization. These included 18 mixed cellularity, 19 nodular sclerosis and six lymphocyte depleted subtypes. pRb expression was seen in lymphocytes, mononuclear Hodgkin's and Reed-Sternberg cells in 67 of the cases. From this study it appears that pRb expression is seen in the majority of cases of Hodgkin's disease: 67/71 (94.4 per cent). Thirty-nine of 43 cases (90.7 per cent) of EBV positive cases were also positive for pRb. The results of this study indicate that pRb immunoexpression is detected in the vast majority of cases of Hodgkin's disease, and that this expression is independent of the EBV status of the case.

Hodgkin Disease↗
PubMed1997

An immunohistochemical analysis of Reed-Sternberg-like cells in posttransplantation lymphoproliferative disorders: the possible pathogenetic relationship to Reed-Sternberg cells in Hodgkin's disease and Reed-Sternberg-like cells in non-Hodgkin's lymphomas and reactive conditions.

The aim of this study was to assess the incidence and immunophenotype of Reed-Sternberg-like (R-S-like) cells in the setting of posttransplantation lymphoproliferative disorders (PTLD). Twenty-eight formalin-fixed, paraffin-embedded cases (17 renal and 11 heart/heart-lung PTLDS) were analyzed for the presence of typical binucleate cells with inclusionlike nucleoli--the Reed-Sternberg phenotype. An immunohistochemical evaluation for the following markers was performed: CD3, CD20, CD79a, CD15, CD30, CD45, EBV-LMP-1, and vimentin. Monoclonality was assessed by staining for light chain restriction. Eleven cases contained R-S-like cells (9 renal and 2 heart/heart-lung PTLD). All 11 cases were positive for CD45 (LCA), EBV-LMP-1, and vimentin. Ten of 11 cases were CD20/CD79a positive, one case being of a null immunophenotype. Nine cases expressed CD30, whereas 0 of 11 were positive for CD15. In nine cases, expression of both kappa and lambda light chains was present; the remaining two cases failed to express either light chain. This study shows that the R-S-like cells encountered in PTLD have an activated B cell immunophenotype, are invariably EBV-LMP-1 positive, are often CD30 positive, and are CD15 negative. This latter immunophenotypic feature separates R-S-like cells from the R-S cells seen in Hodgkin's disease. The strong staining for EBV-LMP-1 in R-S-like cells also indicates a strong association between EBV-LMP and the R-S morphological phenotype in the context of PTLDs.

Adult↗
PubMed1997

Lung carcinomas composed of rhabdoid cells.

Rhabdoid tumours form a distinctive morphological entity that is associated with aggressive biological behaviour. They have been described in several sites and tumour types. This paper presents three new cases of rhabdoid lung cancers. Lung cancers were analysed for the presence of cells with the rhabdoid phenotype: eccentric vesicular nuclei and abundant eosinophilic cytoplasm. Cells displaying this morphology were then subjected to immunohistochemistry and electron microscopy. The relevant clinical data on these cases were then accessed. Three cases conforming to the morphological, immunophenotypic and ultrastructural characteristics of rhabdoid cells were identified. Two of the cases were associated with foci of adenocarcinoma and the remaining case was a large cell neuroendocrine carcinoma. Two of the cases showed rapid clinical courses with the patients dying of disease within 6 months. Lung tumours with a rhabdoid phenotype are uncommon but are noteworthy because of their aggressive behaviour and, hence, poor prognosis.

Adult↗
PubMed1997

Large cell neuroendocrine carcinoma of the thymus.

AIM: We highlight the occurrence of an unusual neuroendocrine tumour, a large cell neuroendocrine carcinoma, arising from the thymus. CASE DETAILS: A 68-year-old man with a history of cigarette smoking had a large mediastinal tumour arising from the thymus removed. Two years later the tumour recurred; it was debulked surgically but the patient died 2 months later: Histological examination of both tumour specimens revealed a tumour with an endocrine pattern, composed of large pleomorphic cells with large nuclei and prominent nucleoli. The mitotic count ranged from 19 to 26 per 10 high-power fields and large tracks of coagulative tumour necrosis were present. The tumour cells were strongly positive for neuron-specific enolase (NSE), chromogranin, CAM5.2 and AE1/3, with cytoplasmic dot-like accentuation for the latter three markers. The tumour fulfilled the criteria for a diagnosis of large cell neuroendocrine carcinoma. CONCLUSIONS: Large cell neuroendocrine carcinoma should be distinguished from atypical carcinoid and small cell carcinoma. It is a distinctive neuroendocrine malignancy with a prognosis between that of atypical carcinoid and small cell carcinoma, and needs to be treated aggressively.

Aged↗
PubMed1997

Mucosal prolapse changes in Hirschsprung's disease.

The aim of this study was to ascertain the incidence of mucosal prolapse changes in Hirschsprung's disease. Twenty-three random, consecutive resection specimens for this condition were analysed for the histological features of prolapse. Eight cases showed histological evidence suggesting mucosal prolapse at the junction between ganglionic and aganglionic bowel. Thickening and splaying of the muscularis mucosae with extension into the lamina propria, and the presence of metaplastic or hyperplastic tubules with goblet cell and cryptal hypertrophy were the dominant histological features found in the eight cases. In addition, an increase in elastic fibres in the lamina propria and diamond-shaped glands were seen to varying degrees in all eight cases. Mucosal prolapse was more prominent in the older patients and is, therefore, related to duration of symptoms. Differential pressures in ganglionic and aganglionic segments of bowel, together with faecal stream and straining are likely to be of pathogenetic significance.

Child↗