scholarly journals The Role of Immunohistochemical Markers for the Diagnosis and Prognosis of Adrenocortical Neoplasms

2021 ◽  
Vol 11 (3) ◽  
pp. 208
Author(s):  
Anna Angelousi ◽  
Georgios Kyriakopoulos ◽  
Fani Athanasouli ◽  
Anastasia Dimitriadi ◽  
Eva Kassi ◽  
...  
Keyword(s):  
Transcriptome Analysis ◽  
Cox Regression ◽  
P53 Protein ◽  
Immunohistochemical Analysis ◽  
Ki 67 ◽  
Diagnosis And Prognosis ◽  
Immunohistochemical Markers ◽  
Small Series ◽  
Morphological Criteria ◽  
Survival And Development

Adrenal cortical carcinoma (ACC) is a rare cancer with poor prognosis that needs to be distinguished from adrenocortical adenomas (ACAs). Although, the recently developed transcriptome analysis seems to be a reliable tool for the differential diagnosis of adrenocortical neoplasms, it is not widely available in clinical practice. We aim to evaluate histological and immunohistochemical markers for the distinction of ACCs from ACAs along with assessing their prognostic role. Clinical data were retrospectively analyzed from 37 patients; 24 archived, formalin-fixed, and paraffin-embedded ACC samples underwent histochemical analysis of reticulin and immunohistochemical analysis of p27, p53, Ki-67 markers and were compared with 13 ACA samples. Weiss and Helsinki scores were also considered. Kaplan−Meier and univariate Cox regression methods were implemented to identify prognostic effects. Altered reticulin pattern, Ki-67% labelling index and overexpression of p53 protein were found to be useful histopathological markers for distinguishing ACAs from ACCs. Among the studied markers, only pathological p53 nuclear protein expression was found to reach statistically significant association with poor survival and development of metastases, although in a small series of patients. In conclusion, altered reticulin pattern and p53/Ki-67 expression are useful markers for distinguishing ACCs from ACAs. Immunohistopathology alone cannot discriminate ACCs with different prognosis and it should be combined with morphological criteria and transcriptome analysis.

Adrenocortical Tumors in Brazilian Children: Immunohistochemical Markers and Prognostic Factors

2005 ◽  
Vol 129 (9) ◽  
pp. 1127-1131 ◽  
Author(s):  
Lourenco Sbragia ◽  
Antonio Goncalves Oliveira-Filho ◽  
Jose Vassallo ◽  
Glauce Aparecida Pinto ◽  
Gil Guerra-Junior ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Clinical Signs ◽  
Immunohistochemical Analysis ◽  
Signs And Symptoms ◽  
Age At Diagnosis ◽  
Ki 67 ◽  
Adrenocortical Tumors ◽  
Immunohistochemical Markers ◽  
Clinical Signs And Symptoms ◽  
Stage 1

Abstract Context.—The behavior of adrenocortical tumors (ACTs) is usually difficult to establish in childhood, and the role of immunomarkers in predicting outcome has not yet been elucidated. Objective.—To investigate the relationship between clinical, pathologic, and immunohistochemical findings and prognosis in a series of children with ACTs. Patients and Methods.—Clinical data were evaluated retrospectively in 33 children with ACTs, including age at diagnosis, sex, time between first symptoms and diagnosis, clinical signs and symptoms, tumor position, and follow-up. Histologic sections were reviewed, each tumor was classified, and staging was performed according to previously published criteria. Immunohistochemical analysis of p53, Ki-67, c-Erb-B2, and Bcl-2 was performed according to previously published techniques. Results.—Sixty-four percent (n = 21) of the patients were female, and the age at diagnosis in the cohort ranged from 2 to 96 months. Virilization alone affected 70% (n = 23) of the patients, and 18 patients had stage 1 disease, 9 had stage 2 disease, and 3 each had stage 3 and stage 4 disease. Female sex and stage 1 and stage 2 disease were associated with good outcome. None of the histopathologic criteria evaluated correctly predicted outcome. Only tumors with a volume exceeding 200 mL were associated with malignant behavior. Because only a small number of tumors expressed the antigens, results of these immunohistochemical tests were considered inconclusive. Conclusion.—In this sample of pediatric ACTs, the clinical and surgical parameters are the most important prognostic factors, while the immunohistochemical markers evaluated were not predictive of outcome.

The role of immunohistochemistry in the diagnosis of cervical intraepithelial neoplasia of different severity

2016 ◽  
pp. 138-140
Author(s):  
S.I. Zhuk ◽  
◽  
O.A. Taran ◽  
A.N. Koshmienskaya ◽  
T.V. Lobastova ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cervical Intraepithelial Neoplasia ◽  
Precancerous Lesions ◽  
Molecular Genetic ◽  
Intraepithelial Neoplasia ◽  
Reproductive Age ◽  
Moderate Degree ◽  
Ki 67 ◽  
The Third ◽  
Diagnosis And Prognosis

The objective: the finding of protein expression of apoptosis regulator BCL-2, Smooth Muscule Actin and the antigen Ki-67 in cervical intraepithelial neoplasia of different severity to optimize the diagnosis and prognosis of the disease. Patients and methods. The study involved 42 women of reproductive age with cervical intraepithelial the neoplasia of the cervix varying degrees applied to the doctor of cervical pathology Zhitomir regional oncologic dispensary. All women (n=42) were divided into groups. The first group included 15 patients (35.7%) with cervical intraepithelial neoplasia with mild. The second group included 13 women (31%) with cervical intraepithelial neoplasia a moderate degree. The third group was represented by patients with cervical intraepithelial neoplasia with severe – 14 respondents (33.3 per cent). Results. Marker BCL-2 in patients of the first group was positive in 7 patients (46.7%), Smooth Muscule Actin was positive in 9 patients (60%) and Ki-67 was diagnosed in 8 of the surveyed women (53.3%). In the second group of BCL-2 was positive in 8 patients (61.5%), Clone 124, Smooth Muscule Actin, Clone 1A4 was positive in 9 patients (69.2%), and Ki-67 was diagnosed in 12 of the surveyed women (92.3%). Marker BCL-2 in patients of the third group was positive in 12 patients (85.7%), Smooth Muscule Actin was positive in 10 patients (71.4%) and Ki-67 was diagnosed in 13 of the surveyed women (92.9% ). Conclusion. Carcinogenesis is associated with molecular genetic damage to the cervix. Some of the products of this process can be used as prognostic and diagnostic markers of tumor progression. Determination of protein expression of apoptosis regulator BCL-2, Smooth Muscule Actin and the antigen Ki-67 in cervical intraepithelial neoplasia makes it possible to accurately verify the diagnosis and to predict the course of pathological changes in the flat epithelium of the cervix. Key words: cervical intraepithelial neoplasia, cervical cancer, morphological diagnostics of precancerous lesions, BCL-2, Smooth Muscule Actin, Ki-67.

scholarly journals Clinical value evaluation of microRNA-324-3p and other available biomarkers in patients with HBV-infection-related hepatocellular carcinoma

2021 ◽  
Author(s):  
Li Zhao ◽  
Qian Yang ◽  
Jianbo Liu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Hepatitis B ◽  
Diagnostic Performance ◽  
Cox Regression ◽  
Hbv Infection ◽  
Healthy Controls ◽  
Survival Prognosis ◽  
Diagnosis And Prognosis ◽  
Hcc Cells

Abstract Background Patients with hepatitis B virus (HBV) infection are at high risk of hepatocellular carcinoma (HCC). This study aimed to evaluate the expression of microRNA-324-3p (miR-324-3p) in HBV-related HCC, and explore the clinical significance of serum miR-324-3p and other available biomarkers in the diagnosis and prognosis of HBV-related HCC. Methods Expression of miR-324-3p in HBV-infection-related cells and patients was estimated using quantitative real-time PCR. The receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic performance of serum miR-324-3p, AFP and PIVKA-II in the differentiation of HBV-related HCC from healthy controls and chronic hepatitis B (CHB). The relationship between serum miR-324-3p and patients’ clinical features was assessed using Chi-square test, and the value of miR-324-3p to predict overall survival prognosis was evaluated using Kaplan-Meier methods and Cox regression assay in patients with HBV-related HCC. Results HBV-related HCC cells had significantly increased miR-324-3p compared with normal and HBV-unrelated HCC cells, and serum miR-324-3p in HCC patients with HBV infection was also higher than that in healthy controls and CHB. Serum miR-324-3p had relatively high diagnostic accuracy for the screening of HCC case with HBV infection, and the combination of miR-324-3p, AFP and PIVKA-II showed the improved diagnostic performance. Additionally, high serum miR-324-2p in HBV-related HCC patients was associated with cirrhosis, tumor size, clinical stage and poor overall survival prognosis. Conclusion Serum increased miR-324-3p may be involved in the progression of HBV-related hepatitis to HCC, and may serve as a candidate biomarker for the diagnosis and prognosis of HBV-related HCC.

Developing a nomogram for predicting intravesical recurrence after radical nephroureterectomy: a retrospective cohort study of mainland Chinese patients

2021 ◽  
Author(s):  
Shicong Lai ◽  
Xingbo Long ◽  
Pengjie Wu ◽  
Jianyong Liu ◽  
Samuel Seery ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Cox Regression ◽  
Upper Tract Urothelial Carcinoma ◽  
Chinese Patients ◽  
Clinicopathological Parameters ◽  
Radical Nephroureterectomy ◽  
Ki 67 ◽  
Data Set ◽  
Mainland Chinese ◽  
Upper Tract

Abstract Objective To evaluate the role of Ki-67 in predicting subsequent intravesical recurrence following radical nephroureterectomy and to develop a predictive nomogram for upper tract urothelial carcinoma patients. Methods This retrospective analysis involved 489 upper tract urothelial carcinoma patients who underwent radical nephroureterectomy with bladder cuff excision. The data set was randomly split into a training cohort of 293 patients and a validation cohort of 196 patients. Immunohistochemical analysis was used to assess the immunoreactivity of the biomarker Ki-67 in the tumor tissues. A multivariable Cox regression model was utilized to identify independent intravesical recurrence predictors after radical nephroureterectomy before constructing a nomographic model. Predictive accuracy was quantified using time-dependent receiver operating characteristic curve. Decision curve analysis was performed to evaluate the clinical benefit of models. Results With a median follow-up of 54 months, intravesical recurrence developed in 28.2% of this sample (n = 137). Tumor location, multifocality, pathological T stage, surgical approach, bladder cancer history and Ki-67 expression levels were independently associated with intravesical recurrence (all P < 0.05). The full model, which intercalated Ki-67 with traditional clinicopathological parameters, outperformed both the basic model and Xylinas’ model in terms of discriminative capacity (all P < 0.05). Decision-making analysis suggests that the more comprehensive model can also improve patients’ net benefit. Conclusions This new model, which intercalates the Ki-67 biomarker with traditional clinicopathological factors, appears to be more sensitive than nomograms previously tested across mainland Chinese populations. The findings suggest that Ki-67 could be useful for determining risk-stratified surveillance protocols following radical nephroureterectomy and in generating an individualized strategy based around intravesical recurrence predictions.

scholarly journals Screening the genome for HCC-specific CpG methylation signatures as biomarkers for diagnosis and prognosis evaluation

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Rui-kun Zhang ◽  
Jia-lin Liu
Keyword(s):  
Cox Regression ◽  
Malignant Tumors ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Survival Prediction ◽  
Training Set ◽  
Cpg Sites ◽  
Diagnosis And Prognosis ◽  
Patient Prognosis ◽  
Prognosis Evaluation

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common and invasive malignant tumors in the world. The change in DNA methylation is a key event in HCC. Methods Methylation datasets for HCC and 17 other types of cancer were downloaded from The Cancer Genome Atlas (TCGA). The CpG sites with large differences in methylation between tumor tissues and paracancerous tissues were identified. We used the HCC methylation dataset downloaded from the TCGA as the training set and removed the overlapping sites among all cancer datasets to ensure that only CpG sites specific to HCC remained. Logistic regression analysis was performed to select specific biomarkers that can be used to diagnose HCC, and two datasets—GSE157341 and GSE54503—downloaded from GEO as validation sets were used to validate our model. We also used a Cox regression model to select CpG sites related to patient prognosis. Results We identified 6 HCC-specific methylated CpG sites as biomarkers for HCC diagnosis. In the training set, the area under the receiver operating characteristic (ROC) curve (AUC) for the model containing all these sites was 0.971. The AUCs were 0.8802 and 0.9711 for the two validation sets from the GEO database. In addition, 3 other CpG sites were analyzed and used to create a risk scoring model for patient prognosis and survival prediction. Conclusions Through the analysis of HCC methylation datasets from the TCGA and Gene Expression Omnibus (GEO) databases, potential biomarkers for HCC diagnosis and prognosis evaluation were ascertained.

scholarly journals Novel Benzenesulfonate Scaffolds with a High Anticancer Activity and G2/M Cell Cycle Arrest

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1790
Author(s):  
Katarzyna Malarz ◽  
Jacek Mularski ◽  
Michał Kuczak ◽  
Anna Mrozek-Wilczkiewicz ◽  
Robert Musiol
Keyword(s):  
Cell Cycle ◽  
Anticancer Activity ◽  
Cell Cycle Arrest ◽  
Anticancer Agents ◽  
Kinase Inhibitors ◽  
P53 Protein ◽  
Structural Similarity ◽  
M Cell ◽  
Cycle Arrest ◽  
Small Series

Sulfonates, unlike their derivatives, sulphonamides, have rarely been investigated for their anticancer activity. Unlike the well-known sulphonamides, esters are mainly used as convenient intermediates in a synthesis. Here, we present the first in-depth investigation of quinazoline sulfonates. A small series of derivatives were synthesized and tested for their anticancer activity. Based on their structural similarity, these compounds resemble tyrosine kinase inhibitors and the p53 reactivator CP-31398. Their biological activity profile, however, was more related to sulphonamides because there was a strong cell cycle arrest in the G2/M phase. Further investigation revealed a multitargeted mechanism of the action that corresponded to the p53 protein status in the cell. Although the compounds expressed a high submicromolar activity against leukemia and colon cancers, pancreatic cancer and glioblastoma were also susceptible. Apoptosis and autophagy were confirmed as the cell death modes that corresponded with the inhibition of metabolic activity and the activation of the p53-dependent and p53-independent pathways. Namely, there was a strong activation of the p62 protein and GADD44. Other proteins such as cdc2 were also expressed at a higher level. Moreover, the classical caspase-dependent pathway in leukemia was observed at a lower concentration, which again confirmed a multitargeted mechanism. It can therefore be concluded that the sulfonates of quinazolines can be regarded as promising scaffolds for developing anticancer agents.

Immunohistochemical study of p53 expression in endometrial carcinomas: correlation with markers of proliferating cells and clinicopathologic features

1993 ◽  
Vol 3 (6) ◽  
pp. 363-368 ◽  
Author(s):  
T. Hachisuga ◽  
K. Fukuda ◽  
M. Uchiyama ◽  
N. Matsuo ◽  
T. Iwasaka ◽  
...  
Keyword(s):  
Dna Polymerase ◽  
Proliferative Activity ◽  
P53 Protein ◽  
Myometrial Invasion ◽  
Proliferating Cells ◽  
Ki 67 ◽  
Normal Endometrium ◽  
P53 Expression ◽  
Dna Polymerase Α ◽  
Endometrial Carcinomas

Using anti-p53 (PAb1801 and PAb240), anti-DNA polymerase α and Ki-67 monoclonal antibodies, the expression of p53 was studied in 11 normal endometria, 14 endometrial hyperplasias and 27 endometrial carcinomas and its relationship to the proliferative activity of the tumors was examined. Normal endometria and simple hyperplasias were completely negative for p53. The PAb1801 indices of complex hyperplasias and complex atypical hyperplasias were 2.5±1.8% and 5.0±3.2%, respectively. The PAb1801 indices of grade 1, grade 2 and grade 3 endometrial carcinomas were 10.2±14.2%, 44.4±29/0% and 45.0±32.5%, respectively. These results indicate a progressively enhanced p53 expression in the sequence from normal endometrium, through hyperplasia to carcinoma. A significant correlation between p53 expression and labeling indices of Ki-67 and DNA polymerase α was observed in endometrial carcinomas. The endo-metrial carcinomas with p53 overexpression developed mainly in post-menopausal patients and were frequently high-grade tumors with deep myometrial invasion. These findings may indicate that overexpression of p53 protein contributes to the proliferative activity of the tumor cells.

Expression of p53 Protein and Ki-67 Antigen in Gingival Hyperplasia Induced by Nifedipine and Phenytoin

1999 ◽  
Vol 70 (6) ◽  
pp. 581-586 ◽  
Author(s):  
Keiichi Saito ◽  
Shiro Mori ◽  
Naoko Tanda ◽  
Seizaburo Sakamoto
Keyword(s):  
P53 Protein ◽  
Gingival Hyperplasia ◽  
Ki 67
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