scholarly journals Expression of p53, bcl-2, and ki-67 Proteins in the Inflammatory Regenerative and Dysplastic Epithelial Lesions of Flat Colonic Mucosa

2008 ◽  
Vol 6 (1) ◽  
pp. 39-45 ◽  
Author(s):  
Svjetlana Radović ◽  
Zora Vukobrat-Bijedić ◽  
Ivan Selak ◽  
Mirsad Babić

The aim of the study was to define the distribution of p53, bcl-2 and Ki-67 proteins in the inflammatory-regenerative and dysplastic lesionsof the colon mucosa. The relationship between the presentation of p53, bcl-2 and Ki-67 proteins and the intensity of the inflammatory-regenerative and dysplastic lesions in the colon flat mucosa was investigated as well. Biopsy specimens from 270 patients were examined: 74 were classified as inflammatory-regenerative and 196 as dysplastic lesions (108 mild, 58 moderate, and 30 severe dysplasia). The expression of all three proteins was assessed on the basis of location, quantity, and intensity of immunostaining, by counting antigen positive cells, in comparison with normal mucosa and adenocarcinoma. p53 protein appears only in sporadic cases (6.6%) of severe dysplasia. Bcl-2 expression appears significantly (p<0.005) more often in cases of mild dysplasia (61.1%) compared to inflammatory-regenerative mucosa (14.8%). In cases of mild dysplasia, bcl-2 positive cells were spreading from the lower third to the middle third of the crypts. Bcl-2 expression was maintained through the stadiums of moderate and severe dysplasia (75.8%), where antigen positive cells were found all along the crypts. A significant increase (p<0.005) in the expression of nuclear protein Ki-67 was noticed in the stadiums of moderate (labelling index =26.3) compared to mild dysplasia (labelling index=16.7), and severe (labelling index=36.7) compared to moderate dysplasia, where the zone of cellular proliferation was widen along the whole crypt length. In the process of the development of epithelial dysplasia in the flat mucosa of colon a degree of the gene p53 alteration is low and appears only in sporadic cases of severe dysplasia. Mutation of the bcl-2 gene is involved in the genesis of the lesion but not in its progression to carcinoma. Increased expressionof Ki-67 protein speaks in favour of an increased cellular proliferation which, together with the above mentioned mechanisms, is involved in the process of occurrence and progression of epithelial dysplasia in the flat mucosa of colon.

2003 ◽  
Vol 3 (1) ◽  
pp. 30-35
Author(s):  
Svjetlana Radović ◽  
Ivan Selak ◽  
Mirsad Babić ◽  
Željka Knežević ◽  
Zora Vukobrat-Bijedić

The aim of this research is to establish by immunohistochemistry if there is a change in the expression of collagen type IV, as a substitute of basement membrane, in development of epithelial dysplasia in chronically inflamed colon mucosa.Methods. Biopsy specimens from 270 patients were examined: 74 were classified as inflammatory-regenerative and 196 as dysplastic lesions. There were 108 cases of mild dysplasia, 58 cases of moderate and 30 cases severe dysplasia, respectively. Visualisation of collagen IV and its way of expression within basement membrane of glandular crypts was performed by immunohistochemistry and then compared with findings in normal colon mucosa and colon adenocarcinoma tissue.Results. Changes in the expression of collagen IV comprised of its focal irregularities, diffuse thinning and/or thickening, focal interruptions or its complete absence. Significant changes in the expression of collagen IV in relation to normal mucosa already occur in inflammatory-regenerative mucosa. In mild dysplasia, these changes are more intensive in relation to those in inflammatory altered mucosa as well as at severe dysplasia in relation to moderate dysplasia. Changes in the expression of collagen IV in severe dysplasia are significantly more serious than in moderate dysplasia but are identical to those in colon adenocarcinoma tissue.Conclusion. These findings suggest that change in the expression of collagen IV is in correlation to a degree of epithelial dysplasia that developed in flat chronically inflamed colon mucosa.


2020 ◽  
Vol 9 (02) ◽  
pp. 099-104
Author(s):  
Krishnendu Mondal ◽  
Rupali Mandal ◽  
Badal Chandra Sarkar

Abstract Background Early detection of dysplastic changes within oral potentially malignant disorders is the mainstay to prevent oral cancer. Ki-67 is one of the most useful antigens in this purpose. Aims The study aims were to recognize and mutually compare the proliferative status of idiopathic oral leukoplakia (OL) patches, which presented through different forms of dysplasia and carcinoma. Settings and Design In 4 years of observation, cumulatively 140 OL lesions were included for examination. The wholesome Ki-67 labeling scores in each of the subgroups were calculated. Subjects and Methods The World Health Organization recommended histopathological classification was used to categorize the dysplastic and malignant lesions. Paraffin-embedded tissue sections were processed for Ki-67 immunostaining. The labeling indices (LIs) were quantified semiquantitatively at the site of maximal reactive cells on tissue sections. Statistical Analysis The statistical comparison was performed by means of the SPSS software (Version 16.0 SPSS Inc.). A p-value < 0.05 was considered as the benchmark for statistical significance. Results A steady and significant increment in Ki-67 expression was discovered from dysplastic to malignant OL patches compared with normal mucosa. The labeling differences were significant between normal mucosa and mild dysplasia, as well as between mild, moderate, and severe dysplasia. However, the expression did not differ significantly with the severity of oral cancers. Conclusions Ki-67 is a useful molecular marker of carcinogenesis in OL. It also serves worthwhile in separating marginally dysplastic lesions, such as mild dysplasia or verrucous carcinoma from their benign epigones.


Author(s):  
Madhuresh Kumar ◽  
S Suwasini ◽  
Kabita Chatterjee ◽  
SwapanKumar Purkait ◽  
Dipankar Samaddar ◽  
...  

2005 ◽  
Vol 153 (2) ◽  
pp. 203-205 ◽  
Author(s):  
W M Drake ◽  
D M Berney ◽  
K Kovacs ◽  
J P Monson

We report our findings on markers of cell proliferation (Ki-67 labelling index and topoisomerase-α expression) in a somatotroph pituitary tumour before and after exposure to pegvisomant, a GH receptor antagonist developed for the treatment of acromegaly. Specimens from two separate pituitary operations, separated by a period of 17 years that included 4 years of pegvisomant treatment, were stained for markers of cellular proliferation. Ki-67 labelling index and topoisomerase-α expression were both markedly greater (1–3% compared with 0–0.5% and 15–80% compared with 2–10% respectively) in the pegvisomant-exposed tumour compared with the earlier specimen. Clearly, caution must be exercised when interpreting findings from a single case, particularly one sufficiently refractory to conventional therapies to require treatment with pegvisomant. However, our data reinforce the requirement for careful radiological surveillance of the pituitary in the context of a drug that does not target the tumour responsible and where serum GH cannot serve as a marker of disease activity or tumour size.


1996 ◽  
Vol 110 (5) ◽  
pp. 440-445 ◽  
Author(s):  
Nina Zidar ◽  
Nina Gale ◽  
Andrej Cör ◽  
Vinko Kambič

AbstractIn an attempt to analyse the proliferative activity in benign and malignant laryngeal epithelial lesions, and to determine the relationship to their histologic grade, we studied the expression of proliferative cell nuclear antigen (PCNA) and Ki-67 antigen on 20 squamous carcinomas, and on 30 biopsies of epithelial hyperplasia categorized according to the Kambiˇ-Lenart classification into simple, abnormal, and atypical hyperplasias. In simple hyperplasia, both antibodies stained the nuclei of the occasional cells in the basal layer. In abnormal hyperplasia (mild dysplasia), positive cells occupied up to a third, and in atypical hyperplasia (moderate and severe dysplasia) they occupied from two-thirds to the entire epithelial thickness. In squamous carcinoma, we have found a statistically significant correlation between its grade and the percentage of Ki-67-(p<0.01) and PCNA-(p<0.00001) positive cells. Our results suggest that the proliferative fraction progressively increases with the degree of epithelial hyperplasia and the grade of carcinoma. We conclude that the patterns of immunoreactivity to PCNA and Ki-67 antigen correspond to the histologic grade of both benign and malignant epithelial lesions of the larynx. This method should be regarded as a useful adjunct to traditional histological techniques allowing more objective grading of benign and malignant epithelial lesions.


2004 ◽  
Vol 4 (3) ◽  
pp. 24-30 ◽  
Author(s):  
Svjetlana Radović ◽  
Ivan Selak ◽  
Mirsad Babić ◽  
Zora Vukobrat-Bijedić ◽  
Željka Knežević

The aim of this paper is to establish by immunohistochemistry the expression of keratin 7 in inflammatory-regenerative flat bowel mucosa and in different grades of epithelial dysplasia regarding the sub-units expressed in normal and carcinomatous colonic mucosa. Biopsy specimens from 270 patients were examined: 74 were classified as inflammatory-regenerative changes and 196 as dysplastic lesions. There were 108 cases of mild dysplasia, 58 cases of moderate and 30 cases of severe dysplasia, respectively). Demonstration of location and intensity of cytokeratin 7 staining was performed by immunohistochemistry using monoclonal antibody (anti-cytokeratin 7). Findings of cytokeratin 7 in dysplastic lesions were compared with those in normal mucosa, inflammatory -regenerative mucosa and adenocarcinoma. Cytokeratin 7 is not found in normal colonic mucosa. In inflammatory-regenerative mucosa it was found in solitary cells in small number of cases. It is found in all cases of epithelial dysplasia and its expression showed no difference regarding moderate and severe dysplasia. In few cases of adenocarcinoma, cytokeratin 7 is found in traces and showed minimal staining intensity. Having in mind that cytokeratine 7 is primarily found in dysplastic lesions of the flat colonic mucosa it can be a valuable diagnostic tool in the histological interpretation of epithelial dysplasia.


2014 ◽  
Vol 14 (1) ◽  
pp. 11-14 ◽  
Author(s):  
Arvids Jakovlevs ◽  
Andrejs Vanags ◽  
Dainis Balodis ◽  
Janis Gardovskis ◽  
Ilze Strumfa

Summary Introduction. Heterogeneity is a characteristic feature of malignant tumours. It challenges the treatment regimens as well as can impair the diagnostic accuracy. Glioblastoma multiforme (GBM), a high-grade malignant glial tumour, is known for the extreme morphological heterogeneity giving rise also to the term itself. Aim of the study was to evaluate heterogeneity of pathogenetically and diagnostically important cardinal tumour features, namely, cellular proliferation and tumour suppressor protein expression in GBMs. Material and methods. The study group comprised 101 GBMs, retrospectively identified by archive search. The inclusion criteria comprised validated diagnosis (by World Health Organisation criteria) and lack of prior treatment. Recurrent GBMs as well as other glial and non-glial tumours were excluded from the study. Insufficient tissue materials comprising stereotactic biopsies and tissues affected by widespread necrosis (exceeding 90%) were also excluded. Proliferation activity (by Ki-67) and expression of aberrant p53 protein was detected by immunohistochemical investigation (IHC) of formalin-fixed, paraplast-embedded tumour samples. Polymeric visualisation system was used to detect bound primary antibodies. The expression of each antigen was measured by computed morphometry in at least 200 cells of hot and cold spots in each tumour. The data were expressed as the relative value. Heterogeneity was estimated as the mathematical difference between the highest and lowest expression value in each tumour. Descriptive statistics was applied. The 95% confidence intervals (CI) were determined as well. Results. The highest proliferation activity ranged 15 – 95%; mean 43.9% [95% CI = 40.3 – 47.6]. The lowest proliferation activity ranged 2 – 95%, mean 20.1% [16.8 – 23.4]. The mean proliferation heterogeneity was 23.8% [21.5 – 26.2]; range 0 – 67%. The mean heterogeneity of p53 protein expression was 11.7% [8.9 – 14.6], ranging 0 – 75%. Conclusions. GBM is characterized by marked heterogeneity regarding proliferation rate and expression of p53 protein that may affect diagnostic accuracy and grading of gliomas in small samples of tissue material as well as survival in case of small residual tumour after surgical treatment.


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