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Anatomical Pathology

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Browsing Anatomical Pathology by Subject "Immunohistochemistry."

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    A histopathological and immunohistochemical evaluation of scar basal cell carcinomas.
    (2006) Sydney, Clive.; Ramdial, Pratistadevi K.; Madaree, Anil.
    Infiltrative morphological mimicry at sites of biopsy-proven nodular basal cell carcinoma has been described. The immunoprofile of scar BCCs (scar BCCs,SBCCs) has not been documented. The aim of this study was to assess the histopathological spectrum, stromal (fibronectin, laminin, actin, desmin and vimentin) response and proliferation (bcl-2, MIB1 and p53) status of SBCCs. Twenty nine BCCs occurring in scars, unrelated to previous malignancy (de novo scar BCCS, DN-SBCCs), 27 BCCs that were incompletely excised and regrew at the same site (regrowth scar BCCs, RG-SBCCs) and 25 BCCs that were completely excised with tumour free margins, but recurred at the same site (recurrent scar BCCs, R-SBCCs) were accessed from the files of the Department of Pathology and Plastic and Reconstructive Surgery of the Faculty of Medicine, University of KwaZulu Natal, and formed the basis of this study. The morphological features of DN-SBCCs was pure (3%), predominantly nodular (79%), micronodular (7%) and infiltrative (11 %). RG-SBCCs were predominantly nodular (82%), micronodular (7%) and infiltrative (11%). RSBCCs were predominantly nodular (80%), micronodular (4%) and infiltrative (16%). The majority of DN-SBCCs, RG-SBCCs and R-SBCCs showed intact basement membrane laminin staining, while two (7%) DN-SBCCs showed 1 + and 2+ loss of basement membrane laminin staining. Three (11 %) and two (8%) RG-SBCCs and R-SBCCs,respectively, showed 2+ or 3+ basement membrane laminin discontinuity. The majority of DN-SBCCs (83%), RGSBCCs (75%) and R-SBCCs (88%) were actin negative. No desmin immunopositivity was demonstrated in the epithelial or stromal components of DN-SBCCs, RG-SBCCs and R-SBCCs. All BCC groups showed high 3+ or 4+ vimentin immunopositivity. The majority (>50%) of the SBCCs showed low (2+) bcl-2 immunopositivity. There was no significant difference in p53 immunopositivity in all SBCCs. SBCCs demonstrate phenotypic and immunophenotypic heterogeneity. That DN-SBCCs with the infiltrative and micronodular patterns have not recurred implies that the histomorphology is a pseudo-aggressive pattern. A similar view could pertain to RG-SBCCs, but because the scar did not cicatrise the incompletely excised BCC implies that the histomorphology of RG-BCC may be a potentially more aggressive phenotype. The recurrence of a completely excised basal cell carcinoma may be viewed as a feature of an aggressive tumour, especially when the recurrent BCC contains micronodular and infiltrative components. However, as most R-SBCCs occurred at head and neck sites that are exposed to ultraviolet light, it is also possible that these are simply new BCCs occurring within scars in head and neck sites prone to BCCs. Furthermore, these R-SBCCs were not destructive tumours. CONCLUSION: None of the infiltrative foci of DN-SBCCs demonstrated laminin loss. Three of 5 with intra-epithelial actin immunopositivity also demonstrated low bcl-2 and high p53 staining, immunoprofiling these with an aggressive infiltrative component. Of 11 RG-SBCCs with high p53 staining, 4 had high p53 staining in the infiltrative component, but only one had a low bcl-2 composite score and low bcl-2 score in the infiltrative focus. In addition, these infiltrative foci demonstrated intraepithelial MSA positivity and a "VA" immunophenotype of the stromal cells, indicating one RG-SBCC with an established, aggressive immunophenotype. Those positive with one or more, but not all, aggressive immunostains, are hypothesised to be RG-SBCCs evolving/developing an aggressive immunophenotype. Only one R-SBCC, with a predominantly infiltrative pattern, had a "full-house" of aggressive immunostaining in the infiltrative foci: low bcl-2, high p53, 2+ laminin discontinuity and intra-epithelial and stromal MSA positivity. Of significance is that 7 with a predominant nodular pattern had a high p53 score. Of these, 5 had high bcl-2 scores. Hence, while high p53 may be a feature of aggressive growth, it is important that this staining be complemented with that of bcl-2, laminin and MSA.
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    An immunohistochemical and microsatellite analysis of nephroblastomas.
    (2008) Govender, Dhirendra.; Chetty, Runjun.
    The aims of this study were: (i) to determine the association between p53, bcl-2, pRb, p21, cyclin A and p-glycoprotein immunoexpression and prognosis, and (ii) to determine the frequency of loss of heterozygosity and microsatellite instability at 11 p, 16q and mismatch repair gene loci and their association with prognosis, in nephroblastomas in South African children. There were 138 cases (111 of whom received preoperative chemotherapy) in the immunohistochemical study and, 70 cases (48 with preoperative chemotherapy) in the microsatellite study. The following monoclonal antibodies were used after heat induced epitope retrieval; p53, bcl-2, pRb, p21, cyclin A and p-glycoprotein. Six polymorphic microsatellite markers were selected from the 11p region, 5 from the 16q region and 6 from the loci of known mismatch repair genes. Automated fluorescent DNA technology was used in the analysis. The results of the immunohistochemical and microsatellite studies were correlated with patient age, gender, preoperative chemotherapy, SlOP histological classification, SlOP histological risk group, clinicopathological stage, patient outcome and survival using X2 , Fisher's exact test, Cox regression model and Kaplan-Meier estimates. The majority of patients presented with advanced disease. Anaplastic tumours and high-risk histology were associated with high disease stage. Mortality was directly related to increasing stage and histological risk group. Multivariate analysis showed that clinicopathological stage was the only factor significantly associated with survival (p<0.001) (hr=5.6, 95%CI: 2.1-14.9). High expression of p53 was more frequent in anaplastic tumours suggesting that p53 mutations are common events in this tumour type (p<0.001). Despite the strong association with tumour histology, there was no association with stage. Although p53 expression was found to be a predictor of survival in the univariate analysis this was not retained in the multivariate analysis. Tumours treated with preoperative chemotherapy showed higher bcl-2 immunoreactivity (p=0.027 but lower levels of pRb (p=0.040) and cyclin A expression (p<0.001). All anaplastic tumours showed high expression of pRb compared to the other histological types (p=0.003). Expression of xxii pRb was significantly associated with survival in the univariate analysis but not in the multivariate analysis. High cyclin A expression was associated with high risk histology (p<0.001). Cyclin A expression was found to be a significant predictor of survival in both the univariate (hr=1.7; 95%CI 1.2-2.4; p=0.002) and multivariate analyses (hr=1.7; 95%CI1.1-2.7; p=0.032). Although tumours with high risk histology were more likely to express high levels of p-glycoprotein, this did not reach significance. LOH at 11 p was seen in 64.7% of 68 informative cases. LOH at 11 p13 was more frequent than LOH at 11p15. LOH for both 11p13 and 11p15 was found in 39.7% of all tumours. MSI at 11 p was seen in 22.1 % of informative cases. The majority showed MSI for one marker only. LOH 16q was seen in 66.7% of 66 informative cases. MSI at 16q was seen in 16.7% of cases. LOH for 016S496 and 016S520 appear to be related to tumour histology and risk group. The most frequent locus for LOH was 16q21-22, which is known to harbour important genes, such as, E2F4 and E-cadherin. LOH for MMR markers was seen in 43.5% of 69 informative cases. MSI was seen in 11.6% of tumours. In the multivariate analysis there was no significant correlation between LOH at any of the loci studied and survival. There were no tumours with high frequency MSI. Low frequency MSI was of no clinicopathological significance. The following conclusions are made: (i) p53 mutations determined by high p53 expression is a frequent finding in anaplastic tumours, (ii) Bcl-2 may play a role in the chemoresistance of nephroblastomas, (iii) Rb gene alterations are not important in the development of nephroblastoma and anaplasia, (iv) Cyclin A expression is an independent predictor of survival, (v) p-glycoprotein may be responsible for the chemoresistance in a proportion of nephroblastomas, (vi) MSI is a rare occurrence in nephroblastoma and does not play a role in the development of nephroblastoma, (vii) LOH at 11 p and 16q are frequent findings in nephroblastomas, (viii) LOH for the specific 16q markers (016S496 and 016S520) may have an important prognostic role in nephroblastoma.
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    A morphologic and immunohistochemical appraisal of invasive breast carcinomas with neuroendocrine differentiation.
    (2021) Naicker, Nimallen.; Nhlonzi, Gamalenkosi Bonginkosi.; Mwazha, Absalom.
    Background: Invasive breast carcinomas with neuroendocrine differentiation (IBCNED) are a heterogenous group of tumours first recognised, as a distinct entity, by the World Health Organisation (WHO) in 2003. The classification of these tumours has undergone significant changes since they were first described, and the diagnostic criteria has been inconsistent amongst reporting authors. IBCNED have not been studied in the South African context, and this study aims to review the incidence, demographic profile, histopathology and immunohistochemical profile of IBCNED. Materials and Methods: A three-month retrospective study of cases with the diagnosis of invasive breast carcinomas was undertaken to determine the clinicopathologic profile of IBCNED. Results: The mean age of female patients with IBCNED was 55 years. Thirty-five (35/91, 38%) cases were positive for synaptophysin and/or chromogranin A. The tumours showed a histomorphology comparable with invasive breast carcinoma of no special type and were predominantly (33/35, 94%) moderately to poorly differentiated. The predominant molecular subtype, with 91% (33/35), was luminal B . Conclusion: IBCNED show a diverse range of histomorphologic features, similar to those seen in conventional breast carcinomas of no special type, however they do have distinct cytomorphological characteristics and show a predilection for luminal B molecular subtype. A larger cohort is necessary to confirm these findings and to expand knowledge and treatment options.