scholarly journals Alterations in Expression of Cell Surface and Cell Cycle Signaling Molecules in Recurrent Nonmuscle Invasive Bladder Cancers: A Tissue Microarray Expression Analysis

2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 94s-94s
Author(s):  
V. Agrawal ◽  
N. Bharti
Keyword(s):  
Cell Cycle ◽  
Cell Surface ◽  
Surface Proteins ◽  
Proliferation Index ◽  
Beta Catenin ◽  
Ki 67 ◽  
Time To Recurrence ◽  
Recurrent Tumors ◽  
The Mean ◽  
Cell Cycle Signaling

Background: Nonmuscle invasive bladder cancers (NMIBC) are one of the most common urological cancers having a high risk of recurrence and progression. Recurrent tumors may acquire certain molecular alterations responsible for progression of the tumors. Identification of these alterations is important to understand the pathobiology and guide further management. Aim: We studied the differences in expression of cell surface proteins and cell cycle signaling molecules in primary and recurrent NMIBC by immunohistochemistry (IHC) on tissue microarrays (TMA). Methods: Using FFPE tissue, TMA of 82 tumors (40 primary NMIBC and 47 recurrences) were constructed. IHC for growth factor receptors [epidermal growth factor receptor (EGFR), HER2/neu and FGFR3], cell adhesion molecules (E-cadherin and beta-catenin) and cell cycle pathway molecules (p53, p21/WAF1/Cip1 and Ki-67 proliferation index) was performed. A semiquantitative H-score (Histo-score; range 0-300) was calculated according to the intensity (0, negative; 1, weak; 2, moderate; and 3, strong) and percentage of cells stained. < 10% cells showing nuclear p21 expression was considered p21-loss. The differences in expression between the primary and recurrent tumors were analyzed using paired t test. Results: The mean age at presentation was 65.3 ± 13.6 years with a male predominance (n=36). The mean time to recurrence was 33.4 months (range 3-109). Progression in grade and/or stage was seen in 30 (75%) tumors. Time to recurrence was shorter in primary tumors with ≥ 5% Ki-67 proliferation index. There was no significant difference in expression of cell surface proteins between primary and recurrent tumors. Significant p21 loss was seen in recurrent tumors ( P = 0.03) and significantly correlated with loss of surface beta-catenin and nuclear p53 positivity ( P = 0.002). Ki-67 index was higher in recurrent tumors and also correlated with p53 positivity ( P = 0.007). Conclusion: We found no significant differences in expression of cell surface molecules in primary nonmuscle invasive bladder cancers and their recurrences. However, there were significant alterations in expression of molecules of cell cycle signaling pathway and cellular proliferation in recurrent tumors suggesting the role of cell cycle regulators as promising targets in these cancers.

Wnt5a Expression Is Associated With the Tumor Proliferation and the Stromal Vascular Endothelial Growth Factor—An Expression in Non–Small-Cell Lung Cancer

2005 ◽  
Vol 23 (34) ◽  
pp. 8765-8773 ◽  
Author(s):  
Cheng-long Huang ◽  
Dage Liu ◽  
Jun Nakano ◽  
Shinya Ishikawa ◽  
Keiichi Kontani ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell ◽  
Squamous Cell Carcinomas ◽  
Proliferation Index ◽  
Beta Catenin ◽  
Vascular Endothelial ◽  
Small Cell Lung ◽  
Ki 67 ◽  
Wnt5a Expression ◽  
Endothelial Growth Factor

Purpose The Wnt gene family encodes the multifunctional signaling glycoproteins. We performed the present study to investigate the clinical significance of Wnt5a expression in non–small-cell lung cancer (NSCLC). Patients and Methods One hundred twenty-three patients with NSCLC who had undergone resection were investigated. Real-time quantitative reverse transcriptase polymerase chain reaction was performed to evaluate the Wnt5a gene expression. Immunohistochemistry was performed to investigate the Wnt5a protein expression, the Ki-67 proliferation index, tumor angiogenesis, and the expression of beta-catenin and vascular endothelial growth factor-A (VEGF-A). Results Wnt5a gene expression in squamous cell carcinoma was significantly higher than that in adenocarcinoma (P < .0001). There was a significant correlation between the normalized Wnt5a gene expression ratio and the intratumoral Wnt5a protein expression (r = 0.729; P < .0001). The intratumoral Wnt5a expression was significantly correlated with the Ki-67 proliferation index (r = 0.708; P < .0001). In contrast, no correlation was observed between the intratumoral Wnt5a expression and tumor angiogenesis. Furthermore, the intratumoral Wnt5a expression was significantly correlated with the stromal expression of beta-catenin (r = 0.729; P < .0001) and VEGF-A (r = 0.661; P < .0001). In addition, the stromal VEGF-A expression was also correlated with Ki-67 proliferation (r = 0.627; P < .0001). Cox regression analyses demonstrated Wnt5a status to be a significant prognostic factor for NSCLC patients (P = .0193), especially for patients with squamous cell carcinomas (P = .0491). Conclusion The present study revealed that an overexpression of Wnt5a could produce more aggressive NSCLC, especially in squamous cell carcinomas, during tumor progression.

scholarly journals Correlation of diffusion MRI with the Ki-67 index in non-small cell lung cancer

2015 ◽  
Vol 49 (3) ◽  
pp. 250-255 ◽  
Author(s):  
Adem Karaman ◽  
Irmak Durur-Subasi ◽  
Fatih Alper ◽  
Omer Araz ◽  
Mahmut Subasi ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Negative Correlation ◽  
Small Cell ◽  
Proliferation Index ◽  
Tissue Sampling ◽  
Small Cell Lung ◽  
Ki 67 ◽  
The Mean

Abstract Background. The primary objective of the study was to evaluate the association between the minimum apparent diffusion coefficient (ADCmin) and Ki-67, an index for cellular proliferation, in non-small cell lung cancers. Also, we aimed to assess whether ADCmin values differ between tumour subtypes and tissue sampling method. Methods. The patients who had diffusion weighted magnetic resonance imaging (DW-MRI) were enrolled retrospectively. The correlation between ADCmin and the Ki-67 index was evaluated. Results. Ninety three patients, with a mean age 65 ± 11 years, with histopathologically proven adenocarcinoma and squamous cell carcinoma of the lungs and had technically successful DW-MRI were included in the study. The numbers of tumour subtypes were 47 for adenocarcinoma and 46 for squamous cell carcinoma. There was a good negative correlation between ADCmin values and the Ki-67 proliferation index (r = −0.837, p < 0.001). The mean ADCmin value was higher and the mean Ki-67 index was lower in adenocarcinomas compared to squamous cell carcinoma (p < 0.0001). There was no statistical difference between tissue sampling methods. Conclusions. Because ADCmin shows a good but negative correlation with Ki-67 index, it provides an opportunity to evaluate tumours and their aggressiveness and may be helpful in the differentiation of subtypes non-invasively.

scholarly journals Validation of Predictive Models for Autoimmune Encephalitis-Related Antibodies to Cell-Surface Proteins Expressed in Neurons: A Retrospective Study Based in a Hospital

2021 ◽  
Vol 12 ◽  
Author(s):  
Siqi Ding ◽  
Jiaoni Gong ◽  
Jiahe Lin ◽  
Yi Wang ◽  
Yingjie Hua ◽  
...  
Keyword(s):  
Cell Surface ◽  
Predictive Model ◽  
Predictive Models ◽  
Area Under The Curve ◽  
Autoimmune Encephalitis ◽  
Autoimmune Disorder ◽  
Surface Proteins ◽  
Cutoff Score ◽  
Cell Surface Proteins ◽  
The Mean

Objective: Autoimmune encephalitis (AE) is a severe but treatable autoimmune disorder that is diagnosed by antibody (Ab) testing. However, it is unrealistic to obtain an early diagnosis in some areas since the Ab status cannot be immediately determined due to time and technology restrictions. In our study, we aimed to validate the Antibody Prevalence in Epilepsy and Encephalopathy (APE2) score among patients diagnosed with possible AE as a predictive model to screen AE patients with antibodies to cell-surface proteins expressed in neurons.Methods: A total of 180 inpatients were recruited, and antibodies were detected through serological and/or cerebrospinal fluid (CSF) evaluations. The APE2 score was used to validate the predictive models of AE with autoantibodies.Results: The mean APE2 score in the Ab-positive cases was 7.25, whereas the mean APE2 score in the Ab-negative cases was 3.18 (P &lt; 0.001). The APE2 score had a receiver operating characteristic (ROC) area under the curve of 0.924 [P &lt; 0.0001, 95% confidence interval (CI) = 0.875–0.973]. With a cutoff score of 5, the APE2 score had the best psychometric properties, with a sensitivity of 0.875 and a specificity of 0.791.Conclusion: The APE2 score is a predictive model for AE with autoantibodies to cell-surface proteins expressed in neurons and was validated and shown to have high sensitivity and specificity in our study. We suggest that such a model should be used in patients with a suspected diagnosis of AE, which could increase the detection rate of Abs, reduce testing costs, and help patients to benefit from treatment quickly.

scholarly journals Tumor-Associated Protein Profiles in Kaposi Sarcoma and Mimicking Vascular Tumors, and Their Pathological Implications

2019 ◽  
Vol 20 (13) ◽  
pp. 3142 ◽  
Author(s):  
Kyoung Bun Lee ◽  
Kyu Sang Lee ◽  
Hye Seung Lee
Keyword(s):  
Cell Cycle ◽  
Kaposi Sarcoma ◽  
Vascular Lesions ◽  
Vascular Tumors ◽  
Beta Catenin ◽  
Protein Profiles ◽  
Ki 67 ◽  
Rich Cluster ◽  
Galectin 3 ◽  
Cell Cycle Inhibitors

We investigated protein profiles specific to vascular lesions mimicking Kaposi sarcoma (KS), based on stepwise morphogenesis progression of KS. We surveyed 26 tumor-associated proteins in 130 cases, comprising 39 benign vascular lesions (BG), 14 hemangioendotheliomas (HE), 37 KS, and 40 angiosarcomas (AS), by immunohistochemistry. The dominant proteins in KS were HHV8, lymphatic markers, Rb, phosphorylated Rb, VEGF, and galectin-3. Aberrant expression of p53, inactivation of cell cycle inhibitors, loss of beta-catenin, and increased VEGFR1 were more frequent in AS. HE had the lowest Ki-67 index, and the inactivation rates of cell cycle inhibitors in HE were between those of AS and BG/KS. Protein expression patterns in BG and KS were similar. Clustering analysis showed that the 130 cases were divided into three clusters: AS-rich, BG-rich, and KS-rich clusters. The AS-rich cluster was characterized by high caveolin-1 positivity, abnormal p53, high Ki-67 index, and inactivated p27. The KS-rich cluster shared the features of KS, and the BG-rich group had high positive expression rates of galectin-3 and low bcl2 expression. In conclusion, although the rate was different, AS and HE tended to have less cell cycle marker expression than KS, and features of BG and activated KS cell signaling were similar.

The Ki-67 Proliferation Index as a Marker of Time to Recurrence in Intracranial Meningioma

Neurosurgery ◽  
2021 ◽  
Vol 89 (Supplement_2) ◽  
pp. S58-S58
Author(s):  
Christian Mirian ◽  
Simon Skyrman ◽  
Jiri Bartek ◽  
Lasse Rehné Jensen ◽  
Lars Kihlström ◽  
...  
Keyword(s):  
Proliferation Index ◽  
Intracranial Meningioma ◽  
Ki 67 ◽  
Time To Recurrence

Hemangiomas and Angiosarcomas of the Breast: Diagnostic Utility of Cell Cycle Markers With Emphasis on Ki-67

2007 ◽  
Vol 131 (4) ◽  
pp. 538-544 ◽  
Author(s):  
Sandra J. Shin ◽  
Martin Lesser ◽  
Paul Peter Rosen
Keyword(s):  
Cell Cycle ◽  
Cyclin D1 ◽  
Sensitivity And Specificity ◽  
Cutoff Point ◽  
Vascular Lesions ◽  
Vascular Tumors ◽  
Low Grade ◽  
Ki 67 ◽  
Mean Values ◽  
The Mean

Abstract Context.—Vascular tumors comprise a minor subgroup of tumors arising in the breast and represent variants of hemangiomas and angiosarcomas. Diagnostic challenges may arise when differentiating hemangiomas from types I and II angiosarcomas. Ki-67 expression has been used as an adjunct to distinguish between benign and malignant lesions exhibiting histologic overlap at various anatomic sites. Objective.—To investigate the utility of Ki-67 and other cell cycle regulatory proteins (S-phase kinase-associated protein 2 [Skp2], p27, and cyclin D1) in the differential diagnosis of mammary vascular lesions. Design.—Thirty-four vascular tumors (21 hemangiomas and 13 angiosarcomas) of the breast were studied. The Ki-67 index and immunoreactivity for Skp2, p27, and cyclin D1 were determined in each case. Appropriate statistical methods were used. Results.—The mean value of Ki-67 index was statistically different when comparing hemangiomas and angiosarcomas (P &lt; .001). Angiosarcomas were typically positive for Skp2, whereas hemangiomas were negative (P &lt; .001). Sensitivity and specificity cutoffs for Ki-67 index to distinguish hemangiomas from angiosarcomas showed a candidate cutoff point of 175. The mean values of Ki-67 of low-grade angiosarcomas were significantly different from all hemangiomas (P &lt; .001) and also different from the subset of atypical hemangiomas (P = .02). Sensitivity and specificity cutoffs for Ki-67 index to distinguish all hemangiomas from low-grade angiosarcomas showed a candidate cutoff point between 150 and 175. Among angiosarcomas, positivity for Ki-67 was inversely related to that of p27 but not to Skp2 or cyclin D1. This was also true among hemangiomas. Conclusions.—Ki-67 index can be used as a diagnostic tool to distinguish between benign and malignant vascular lesions of the breast. This can be particularly helpful in cases of histologic overlap such as low-grade angiosarcoma and hemangioma.

scholarly journals Effects of tyrosine kinase inhibitor-masitinib mesylate on canine mammary tumour cell lines

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Fulya Ustun-Alkan ◽  
Tülay Bakırel ◽  
Oya Üstüner ◽  
Ceren Anlas ◽  
Suzan Cinar ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Dna Fragmentation ◽  
Cell Lines ◽  
Kinase Inhibitor ◽  
Flow Cytometric Analysis ◽  
Proliferation Index ◽  
Dependent Manner ◽  
Ki 67

Abstract Introduction Masitinib mesylate, a selective tyrosine kinase inhibitor of the c-KIT receptor, is used for the treatment of mast cell tumours in dogs. Masitinib has previously been investigated in various cancers; however, its potential anticancer effect in canine mammary tumours (CMTs) is unknown. In the present paper, we investigated the antiproliferative effect of masitinib in CMT cells and its possible mechanisms of action. Material and Methods The effect of masitinib on the proliferation of CMT-U27 and CMT-U309 cells was assessed by MTT assay and DNA fragmentation. Flow cytometric analysis was used to measure the effect of masitinib on apoptosis and the cell cycle. Additionally, vascular endothelial growth factor levels (VEGF) were measured, and the proliferation marker Ki-67 was visualised in immunocytochemical stainings in CMT cells. Results Treatment with masitinib inhibited the proliferation of CMT cells in a concentration-dependent manner. Maximal apoptotic activity and DNA fragmentation were observed at approximately IC50 of masitinib in both cell lines. In addition, cell cycle distribution was altered and VEGF levels and Ki-67 proliferation indices were decreased in masitinib-treated cells in comparison with control cells. Conclusion In this study, masitinib suppressed cell proliferation concomitantly via induction of apoptosis and cell cycle arrest by decreasing VEGF levels and the Ki-67 proliferation index in CMT-U27 and CMT-U309 cells in vitro, suggesting its potential as a therapeutic tool in the clinical setting of mammary cancer treatment in dogs.

scholarly journals Immunohistochemical Analyses of Cell Cycle-related Proteins, Apoptosis, and Proliferation in Pituitary Adenomas

2001 ◽  
Vol 49 (9) ◽  
pp. 1193-1194 ◽  
Author(s):  
Hiromichi Nakabayashi ◽  
Ichiro Sunada ◽  
Mitsuhiro Hara
Keyword(s):  
Cell Cycle ◽  
Pituitary Adenomas ◽  
Immunohistochemical Analysis ◽  
Cyclin A ◽  
Proliferative Potential ◽  
Ki 67 ◽  
Recurrent Group ◽  
Significant Difference ◽  
The Mean ◽  
Related Proteins

To analyze the cell cycle regulatory mechanisms in the growth of pituitary adenomas, we investigated immunohistochemically the expression of the cell cycle-related proteins cyclin A and p27 in 48 pituitary adenomas. The frequency of apoptosis and the proliferative potential were also examined. The percentage of apoptotic cells was evaluated by immunohistochemical analysis using the anti-single-strand DNA antibody. The proliferative potential was assessed using the anti-Ki-67 antibody. The mean cyclin A labeling index (LI) for the non-recurrent group was 1.03% and for the recurrent group 2.31%. A positive linear correlation between cyclin A LI and Ki-67 LI was found. The mean p27 LI for the non-recurrent group was 67.4% and for the recurrent group 47.0%. There were significant differences in cyclin A LI and p27 LI between the non-recurrent group and the recurrent group. The mean apoptotic rate for the non-recurrent group was 0.87% and for the recurrent group 1.05%. There was no significant difference. Multivariate regression analysis revealed that high cyclin A LI and high Ki-67 LI were significant factors for shorter progression-free survival. The results suggest that the cyclin A LI is a useful prognostic factor in pituitary adenomas. (J Histochem Cytochem 49:1193–1194, 2001)

The Ki-67 Proliferation Index as a Marker of Time to Recurrence in Intracranial Meningioma

Neurosurgery ◽  
2020 ◽  
Author(s):  
Christian Mirian ◽  
Simon Skyrman ◽  
Jiri Bartek ◽  
Lasse Rehné Jensen ◽  
Lars Kihlström ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
De Novo ◽  
Proliferation Index ◽  
Intracranial Meningioma ◽  
Recurrence Rates ◽  
Ki 67 ◽  
Who Grade ◽  
Risk Of Recurrence ◽  
Time To Recurrence ◽  
Significant Difference

Abstract BACKGROUND There are examples of incongruence between the WHO grade and clinical course in meningioma patients. This incongruence between WHO grade and recurrence has led to search for other prognostic histological markers. OBJECTIVE To study the correlation between the Ki-67 proliferative index (PI), risk of recurrence, and recurrence rates in meningioma patients. METHODS We prospectively collected pathological diagnosis of de novo consecutive meningiomas. In total, we followed 159 patients with clinical controls until recurrence, death, or emigration. We estimated the correlation between risk of recurrence and Ki-67 PI when adjusted for age at diagnosis, sex, WHO grade, extent of surgical resection, and tumor location. We estimated the cumulative incidence of recurrence when considering death without recurrence a competing risk. We report recurrence rates per 100 person-years. RESULTS A 1%-point increase of Ki-67 PI yielded a hazard ratio of 1.12 (95% CI: 1.01-1.24) in a multivariate analysis. The cumulative incidence of recurrence was 3% for Ki-67 0% to 4% vs 19% for Ki-67 &gt; 4% meningiomas after 1 yr, but 24% vs 35%, respectively, after 10 yr. There was no significant difference in mean Ki-67 PI between nonrecurrent and recurrent meningioma in a 2-sample t-test (P = .08). The strongest relationship was detected between Ki-67 PI and time to recurrence: Ki-67 &lt; 4% meningiomas recurred after median 4.8 yr, compared to 0.60 to 0.75 yr for patients with higher Ki-67 PI. CONCLUSION Ki-67 PI was a marker for time to recurrence rather than a predictor of recurrence. Ki-67 PI may be utilized for patient tailored follow-up.

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