scholarly journals Expression of regulatory proteins and proliferative activity in relation to phenotypic characteristics of upper urothelial carcinoma

2011 ◽  
Vol 68 (7) ◽  
pp. 567-574 ◽  
Author(s):  
Zana Dolicanin ◽  
Ljubinka Jankovic-Velickovic ◽  
Biljana Djordjevic ◽  
Milan Visnjic ◽  
Ivana Pesic ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Molecular Markers ◽  
Urothelial Carcinoma ◽  
Cyclin D1 ◽  
Regulatory Proteins ◽  
High Expression ◽  
Phenotypic Characteristics ◽  
Ki 67 ◽  
Altered Expression ◽  
Her 2

Background/Aim. Deregulation of the normal cell cycle is common in upper urothelial carcinoma (UUC). The aim of this study was to investigate the expression of regulatory proteins of the cell cycle (p53, p16, cyclin D1, HER-2) and proliferative Ki-67 activity in UUC, and to determine their interaction and influence on the phenotypic characteristics of UUC. Methods. In 44 patients with UUC, histopathological and immunohistochemical analyses (p53, p16, cyclin D1, HER-2, and Ki-67) of tumors were done. Results. Overexpression/ altered expression of p53, p16, cyclin D1 or HER-2 was detected in 20%, 57%, 64%, and 57% of tumors, respectively. Eleven (25%) UUC had a high proliferative Ki-67 index. Forty patients (91%) had at least one marker altered, while four (9%) tumors had a wild-type status. Analysis of relationship between expressions of molecular markers showed that only high expression of p53 was significantly associated with altered p16 activity (p < 0.05). High Ki-67 index was associated with the high stage (p < 0.005), solid growth (p < 0.01), high grade (p < 0.05), and multifocality p < 0.05) of UUC, while high expression of p53 was associated with the solid growth (p < 0.05). In regression models that included all molecular markers and phenotypic characteristics, only Ki-67 correlated with the growth (p < 0.0001), stage (p < 0.01), grade (p < 0.05) and multifocality (p < 0.05) of UUC; Ki-67 and HER-2 expression correlated with the lymphovascular invasion (p < 0.05). Conclusions. This investigation showed that only negative regulatory proteins of the cell cycle, p53 and p16, were significantly associated in UUC, while proliferative marker Ki-67 was in relation to the key phenotypic characteristics of UUC in the best way.

Altered Expression of G1 Regulatory Proteins in Human Soft Tissue Sarcomas

2002 ◽  
Vol 126 (5) ◽  
pp. 567-573 ◽  
Author(s):  
Jinyoung Yoo ◽  
Sonya Y. Park ◽  
Seok Jin Kang ◽  
Sang In Shim ◽  
Byung Kee Kim
Keyword(s):  
Cell Cycle ◽  
Soft Tissue ◽  
Cyclin D1 ◽  
Soft Tissue Sarcomas ◽  
Tumor Grade ◽  
Regulatory Proteins ◽  
Nuclear Accumulation ◽  
Cyclin D ◽  
P53 Pathway ◽  
Altered Expression

Abstract Context.—Soft tissue sarcomas constitute a heterogeneous group of tumors for which tumorigenesis is not fully understood. Altered cell-cycle regulation may underlie the development and/or progression of human malignancies. However, data concerning the occurrence of cell-cycle aberrations in soft tissue sarcomas are very limited. Objectives.—To detect the abnormal features of cell-cycle regulatory proteins in soft tissue sarcomas and to determine the potential role of these proteins in clinical behavior. Design.—The p53 and Rb–cyclin D pathways were investigated by immunohistochemical studies of p53, mdm2, pRb, p16, cyclin D1, and cdk4 proteins, respectively. Results.—Of the 67 sarcomas analyzed, nuclear accumulation of p53 was detected in 25 samples (37%), and overexpression of mdm2 was found in 16 samples (24%). Both p53 and mdm2 expression correlated with tumor grade. Abnormalities involving the Rb–cyclin D pathway were identified in all of the tumors by the altered expression of either pRb (72%) or p16 (94%). Fourteen (21%) and 64 (96%) cases demonstrated cyclin D1 or cdk4 expression, respectively. Overexpression of cyclin D1 showed an association with pRb and p53. There was no correlation between pRb, p16, cyclin D1, or cdk4 and tumor grade or relapse. Conclusion.—Disturbance in the cell-cycle regulatory system involving the p53 pathway and the Rb–cyclin D pathway is relatively frequent in soft tissue sarcomas and may be a contributing factor in the tumorigenesis of these tumors. The alterations in the Rb–cyclin D pathway probably constitute an early event, whereas the abnormalities in the p53 pathway seem to be involved in tumor progression. It is noteworthy that cyclin D1 may play a key role in linking both pathways.

Expression of Cell Cycle Regulatory Proteins and Analysis of Apoptosis in Normal Nasal Mucosa and in Nasal Polyps

2005 ◽  
Vol 19 (6) ◽  
pp. 549-553 ◽  
Author(s):  
Werner Garavello ◽  
Paola Viganò ◽  
Marco Romagnoli ◽  
Lorenza Sordo ◽  
Emilio Berti ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Nasal Mucosa ◽  
Nasal Polyps ◽  
Normal Mucosa ◽  
Cellular Growth ◽  
Regulatory Proteins ◽  
Biological Behavior ◽  
Proliferating Cells ◽  
Ki 67 ◽  
Sequence Of Events

Background The etiopathogenesis of nasal polyps still is to be clarified. Although hyperplasia is a typical feature of these pathological processes, little attention has been paid to specific aspects of cellular growth in polyps. We have evaluated the expression and localization of some of the regulatory proteins that direct the cell through the specific sequence of events culminating in mitosis or apoptosis in nasal polyps. Methods Twenty samples of nasal polyps and 20 samples of normal nasal mucosa have been analyzed for apoptotic index by detecting the DNA 3’ OH ends deriving from DNA fragmentation. Moreover, they have been evaluated by immunohistochemical staining for expression of Ki-67, cyclins A and B1, p53, p21, p27, murine double minute clone 2, and Bcl-2. Results We have identified a greater proportion of proliferating cells in the lining epithelial cells of the polyps when compared with the normal mucosa as stained with anti–Ki-67 antibodies. An overexpression of p53, MDM2, and Bcl-2 and an increased apoptosis were observed in nasal polyps compared with the normal mucosa, whereas no variation of p27 expression was observed. The p21 and cyclins A and B1 were rarely expressed in both pathological and normal tissue. Conclusion The p53-based control system of cell cycle progression appears to be altered in nasal polyps, potentially leading to an abrogation of the DNA damage checkpoint. Evaluation of the expression of the regulatory proteins that direct the cells throughout their cycle in nasal polyps may allow a better understanding of the biological behavior and clinical outcome of these benign pathological entities.

scholarly journals Non-Small Cell Lung Carcinoma: Cyclin D1, bcl-2, p53, Ki-67 and Her-2 Proteins Expression in Resected Tumors

2007 ◽  
Vol 7 (3) ◽  
pp. 205-211 ◽  
Author(s):  
Svjetlana Radović ◽  
Mirsad Babić ◽  
Mirsad Dorić ◽  
Ajna Hukić ◽  
Suada Kuskunović ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cyclin D1 ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Ki 67 ◽  
P53 Expression ◽  
Biological Potential ◽  
Her 2

The aim of this study was to investigate expression of cyclin D1, bcl-2, p53, Ki-67 and HER-2 proteins in 14 cases of non-small cell lung cancer and to establish their correlation to classical clinico-pathological findings, and alleged prognostic value to estimate biological potential of tumor. Retrospective pilot study of the surgically treated non-small cell lung cancer biopsy specimen, paraffin embedded, used immu-nohistochemical method to demonstrate expression of cyclin D1, bcl-2, p53, Ki-67 and HER-2. Protein quantification was performed by the semi-quantitative method. Achieved results were correlated with classical clinico-pathological parameters, like tumor size, histological type, differentiation level, presence ofvascular invasion and metastasis in regional lymph nodes. Out of 14 cases of non-small cell lung cancer, squamous cell carcinoma was found in 7 patients, giant cell carcinoma in 3, adenocarcinoma in 2, and 1 case of pleomorphic and mucoepidermoid carcinoma. Expression of cyclin D1 was not found, while expression of HER-2 and bcl-2 protein was established in one cases each. p53 expression was noted in 8 cases (57,1%). Statistically positive significant correlation (p<0,05) was found among: presence of lympho-vascular invasion to tumor tissue and appearance of nodal metastasis; proliferation Ki-67 index and level of tumor differentiation, i.e. size of tumor. Other investigated parameters showed no significant statistically dependence. p53 expression was not correlated to any of the investigated parameters what might imply the possibility that there is an independent pathway of this protein expression. Negative expression of bcl-2 protein points out to possibility that it is not included into process of tumor apoptosis, as well as that proteins cyclin D1 and HER-2 are not included into processes of the tumor genesis. Since the prolif-erative activity of the tumor, measured by the expression of Ki-67, is correlated to the gradus and size of the tumor mass, Ki-67 protein can be of a prognostic value to determine biological potential of non-small cell lung cancer.

Multivariate analysis of expression of the microtubule-associated protein, tau, predicts improved progression free and overall survival in patients with metastatic HER-2-negative breast cancers treated with docetaxel and vinorelbine plus filgrastim

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 543-543
Author(s):  
A. M. Gown ◽  
L. C. Goldstein ◽  
P. L. Porter ◽  
R. B. Livingston ◽  
S. Tam ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Progression Free Survival ◽  
High Expression ◽  
Breast Cancers ◽  
Beta Tubulin ◽  
Ki 67 ◽  
Expression Levels ◽  
Her 2

543 Background: Drugs that poison the mitotic spindle, including taxanes and vinca alkaloids, are active agents against breast cancer. Preliminary evidence showed that high expression levels of tau predicted improved PFS and OS in patients with metastatic HER-2-negative breast cancers treated with docetaxel and vinorelbine plus filgrastim. We now tested whether levels of tau and another microtubule associated protein, beta-tubulin, could predict PFS and OS in multivariate analysis using other prognostic marker studies, including ER, PR, p53 and Ki-67 on a tissue microarray (TMA) obtained from patients in the SWOG S0102 trial. Materials and Methods: Immunohistochemistry (IHC) using antibodies to tau, beta-tubulin, ER, PR, p53, and Ki-67 was performed on a TMA constructed from the S0102 paraffin blocks. All markers were scored semiquantitatively from 0 to 3. Progression free survival (PFS) and overall survival (OS) were evaluated using multivariate analysis. Results: A total of 38 patients (41.3%) were evaluated. Tau was positively correlated with ER (r=0.36; p=0.0325) and PR (r=0.63; p<0.0001), but not with beta tubulin (p=0.34), Ki-67 (p=0.58), or age (p=0.73). Beta tubulin was not significantly correlated with any other markers. Adjusting for age, there was a significant effect of tau expression on OS (HR=0.667, p= 0.0193) and PFS (HR=0.653; p=0.0035), with higher tau associated with longer survival. When adjusted for both age and PR, there was a marginally significant effect of tau on OS (HR=0.582; p=0.056) and PFS (HR=0.604; p= 0.065). Beta tubulin was not associated with OS (HR=0.909; p=0.66) and PFS (HR=0.904; p=0.58) adjusted for age. Conclusions: In multivariate analysis, identification of breast cancer specimens showing high expression levels of tau predicts improved PFS and OS in patients with metastatic HER-2-negative breast cancers treated with docetaxel and vinorelbine plus filgrastim. High expression of tau also correlated with PR and ER expression. These results confirm and expand earlier studies of the predictive power of tau in a multivariate analysis using a panel of IHC markers for breast cancer. No significant financial relationships to disclose.

Association of cyclin D2 downregulation with adverse prognostic factors and survival: Analysis of D-type cyclins, cyclin E1, p27, and ki-67 mRNA in breast carcinomas.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22208-e22208
Author(s):  
Helena Brizova ◽  
Marcela Mrhalova ◽  
Roman Kodet
Keyword(s):  
Cell Cycle ◽  
Cyclin D1 ◽  
Cell Cycle Regulation ◽  
Mrna Level ◽  
Breast Carcinomas ◽  
Time To Event ◽  
Cyclin D2 ◽  
Ki 67 ◽  
Quantitative Level ◽  
Cycle Regulation

e22208 Background: In a normal mammary gland D-type and E1 cyclins play a significant role in the cell cycle control. Not surprisingly, they are considered to have an oncogenic potential and belong among the most commonly overexpressed genes in breast cancer. Besides, cyclin D2 overexpression is associated with an inhibition of cyclin D1 phosphorylation and with an increase of the p27 inhibitor. Such a complex cell cycle regulation is realized at the quantitative level and results in the proliferation activity control. Therefore, we analyzed the molecules involved in the cell cycle regulation together with the proliferation marker Ki-67 at the quantitative level. Methods: We examined cyclin D1, D2, D3, E1, and p27 and Ki-67 mRNA level by qRT-PCR in 95 fresh frozen invasive ductal breast carcinomas and in 15 non-neoplastic breast tissues. In patients with the carcinoma we correlated the mRNA levels with the ERBB-2 positivity, estrogen and progesterone receptor status, proliferation rate, cyclin D1 protein expression, CCDN1 gene amplification, grade, lymph node status, tumor size and age at diagnosis. We looked for a correlation with overall survival and time to event in 70 patients with available long term follow-up data. Results: The only significant association found in this analysis related to cyclin D2. In comparison with non-neoplastic controls we observed cyclin D2 mRNA down-regulation in breast carcinomas and it was inversely correlated with a higher tumor grade and its greater size, which are considered as parameters related to a less favorable prognosis. Moreover, cyclin D2 mRNA down-regulation together with cyclin D1 and D3 up-regulation revealed a significant association with decreased overall survival and time to event in multivariate analysis. Conclusions: The data indicate that down-regulated cyclin D2 mRNA correlates with a greater malignant potential of breast carcinoma. Thus, establishing cyclin D2 mRNA level may be used as a prognostically relevant investigation and along with other prognostically related data it has a potential in helping to identify patients with an adverse prognosis. Support CZ.2.16/3.1.00/24022 and 00064203.

Results of immunohistochemical staining for cell cycle regulators predict the recurrence of atypical meningiomas

2014 ◽  
Vol 121 (5) ◽  
pp. 1189-1200 ◽  
Author(s):  
Min Soo Kim ◽  
Kyu Hong Kim ◽  
Eun Hee Lee ◽  
Young Min Lee ◽  
Sung-Hun Lee ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cyclin D1 ◽  
Immunohistochemical Staining ◽  
Regulatory Proteins ◽  
Incomplete Resection ◽  
Presenting Symptoms ◽  
Cell Cycle Regulatory Proteins ◽  
Atypical Meningiomas ◽  
Mib 1

Object The aim of this study was to evaluate the role of certain cell-cycle regulatory proteins in the recurrence of atypical meningiomas. These proteins were analyzed with immunohistochemical staining to identify predisposing factors for the recurrence of atypical meningiomas. Methods The authors retrospectively reviewed the medical records of patients with atypical meningiomas diagnosed in the period from January 2000 to June 2012 at the Department of Neurosurgery at Samsung Changwon Hospital and Dong-A University Medical Center. Clinical data included patient sex and age at the time of surgery, presenting symptoms at diagnosis, location and size of tumor, extent of surgery, use of postoperative radiotherapy, duration of follow-up, and recurrence. Immunohistochemical staining for cell-cycle regulatory proteins (p16, p15, p21, p27, cyclin-dependent kinase [CDK] 4 and 6, phosphorylated retinoblastoma [pRB] protein, and cyclin D1) and proliferative markers (MIB-1 antigen, mitosis, and p53) was performed on archived paraffin-embedded tissues obtained during resection. The recurrence rate and time to recurrence were assessed using Kaplan-Meier analysis. Results Of the 67 atypical meningiomas eligible for analysis, 26 (38.8%) recurred during the follow-up period (mean duration 47.7 months, range 8.4–132.1 months). Immunohistochemically, there was overstaining for p16 in 44 samples (65.7%), for p15 in 21 samples (31.3%), for p21 in 25 samples (37.3%), for p27 in 32 samples (47.8%), for CDK4 in 38 samples (56.7%), for CDK6 in 26 samples (38.8%), for pRB protein in 42 samples (62.7%), and for cyclin D1 in 49 samples (73.1%). Multivariate analysis using the Cox proportional-hazards regression model showed that incomplete resection (HR 4.513, p < 0.001); immunohistochemical understaining for p16 (HR 3.214, p < 0.001); immunohistochemical overstaining for CDK6 (HR 3.427, p < 0.001), pRB protein (HR 2.854, p = 0.008), and p53 (HR 2.296, p = 0.040); and increased MIB-1 labeling index (HR 2.665, p = 0.013) and mitotic index (HR 2.438, p = 0.024) predicted the recurrence of atypical meningiomas after resection. Conclusions Findings in this study indicated that p16, CDK6, and pRB protein were associated with the recurrence of atypical meningiomas.

scholarly journals Effect of Human Papillomavirus on Cell Cycle–Related Proteins p16, Ki-67, Cyclin D1, p53, and ProEx C in Precursor Lesions of Cervical Carcinoma

2009 ◽  
Vol 132 (3) ◽  
pp. 378-390 ◽  
Author(s):  
Pablo Conesa-Zamora ◽  
Asunción Doménech-Peris ◽  
Francisco J. Orantes-Casado ◽  
Sebastián Ortiz-Reina ◽  
Laura Sahuquillo-Frías ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Human Papillomavirus ◽  
Cyclin D1 ◽  
Cervical Carcinoma ◽  
Precursor Lesions ◽  
Ki 67 ◽  
Related Proteins

scholarly journals Intestinal cell kinase, a MAP kinase-related kinase, regulates proliferation and G1 cell cycle progression of intestinal epithelial cells

2009 ◽  
Vol 297 (4) ◽  
pp. G632-G640 ◽  
Author(s):  
Zheng Fu ◽  
Jungeun Kim ◽  
Alda Vidrich ◽  
Thomas W. Sturgill ◽  
Steven M. Cohn
Keyword(s):  
Cell Cycle ◽  
Epithelial Cells ◽  
Cyclin D1 ◽  
Intestinal Epithelial Cells ◽  
Protein Translation ◽  
Initiation Factor ◽  
Intestinal Cell ◽  
Intestinal Epithelial ◽  
Altered Expression ◽  
Intestinal Cell Kinase

Intestinal cell kinase (ICK), originally cloned from the intestine and expressed in the intestinal crypt epithelium, is a highly conserved serine/threonine protein kinase that is similar to mitogen-activated protein kinases (MAPKs) in the catalytic domain and requires dual phosphorylation within a MAPK-like TDY motif for full activation. Despite these similarities to MAPKs, the biological functions of ICK remain unknown. In this study, we report that suppression of ICK expression in cultured intestinal epithelial cells by short hairpin RNA (shRNA) interference significantly impaired cellular proliferation and induced features of gene expression characteristic of colonic or enterocytic differentiation. Downregulation of ICK altered expression of cell cycle regulators (cyclin D1, c-Myc, and p21Cip1/WAF1) of G1-S transition, consistent with the G1 cell cycle delay induced by ICK shRNA. ICK deficiency also led to a significant decrease in the expression and/or activity of p70 ribosomal protein S6 kinase (S6K1) and eukaryotic initiation factor 4E (eIF4E), concomitant with reduced expression of their upstream regulators, the mammalian target of rapamycin (mTOR) and the regulatory associated protein of mTOR (Raptor). Furthermore, ICK interacts with the mTOR/Raptor complex in vivo and phosphorylates Raptor in vitro. These results suggest that disrupting ICK function may downregulate protein translation of specific downstream targets of eIF4E and S6K1 such as cyclin D1 and c-Myc through the mTOR/Raptor signaling pathway. Taken together, our findings demonstrate an important role for ICK in proliferation and differentiation of intestinal epithelial cells.

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