Cancer Research and Treatment

Original Articles

Prognostic Role of Rb, p16, Cyclin D1 Proteins in Soft Tissue Sarcomas: Byoung Yong Shim, Jinyoung Yoo, Yeon-Soo Lee, Young Sun Hong, Hoon-Kyo Kim, Jin-Hyoung Kang; Cancer Res Treat. 2010;42(3):144-150. Published online September 30, 2010; DOI: https://doi.org/10.4143/crt.2010.42.3.144

Purpose

The aim of this study was to determine the expressions of Rb, p16, and cyclin D1 in soft tissue sarcomas, and we also wanted to identify the prognostic factors according to the clinicalpathologic features.

Materials and Methods

We reviewed the charts and radiographic films of 66 sarcoma patients. Tissue samples were collected from these patients. Immunochemistry was performed using formalin-fixed, paraffin-embedded tissue samples to examine the expressions of p16, Rb, and cyclin D1 proteins.

Results

The median duration of overall survival was 47.8 months (range, 20.0 to 70.7 months) and the 5 years survival rate was 39%. As for the correlation between the degree of immunohistochemical staining for Rb protein and the histological tumor grades, there was a significant difference with a p-value of 0.019. However, no significant correlation was shown for p16 and cyclin D1. The overall survival duration of the Rb negative group (staining cell <20%) and the heterogeneous group (cell staining 20 to 80%) was 53.5±6.6 months and the overall survival duration of the Rb homogeneous group was 18.3±6.4 months, and there was a significant difference with a p-value of 0.016. However, no significant difference was shown between the survival rate according to the p16 and cyclin D1 expressions. On the multivariate analysis that was done with Rb, p16, the tumor size, grade and site, and patient age, the Rb gene expression was the most significant independent prognostic factor with a risk ratio of 3.01 (p=0.04).

Conclusion

The expression of Rb protein was correlated with the histologic grade and overall survival of patients with soft tissue sarcomas.

Citations

Citations to this article as recorded by

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Mala Sagar, Rita Yadav, Pankaj Deval, Madhu Kumar, Malti K Maurya, Sumaira Qayoom
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Jaffar Khan, Liang Cheng, Michael G. House, Shunhua Guo
Current Oncology.2021; 28(6): 5295. CrossRef
Co-expression of MDM2 and CDK4 in transformed human mesenchymal stem cells causes high-grade sarcoma with a dedifferentiated liposarcoma-like morphology
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Laboratory Investigation.2019; 99(9): 1309. CrossRef
Prognostic significance of p16INK4a alteration in soft tissue sarcomas: A meta-analysis
Gang Lin, Yue Lou
Indian Journal of Cancer.2017; 54(3): 580. CrossRef
GATA3 Expression Is a Poor Prognostic Factor in Soft Tissue Sarcomas
Toshiaki Haraguchi, Hiroaki Miyoshi, Koji Hiraoka, Shintaro Yokoyama, Yukinao Ishibashi, Toshihiro Hashiguchi, Koutaro Matsuda, Tetsuya Hamada, Takahiro Okawa, Naoto Shiba, Koichi Ohshima, Ichiro Aoki
PLOS ONE.2016; 11(6): e0156524. CrossRef
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Elisabetta Pennacchioli, Giulio Tosti, Massimo Barberis, Tommaso M. De Pas, Francesco Verrecchia, Claudia Menicanti, Alessandro Testori, Giovanni Mazzarol
Clinical & Experimental Metastasis.2012; 29(7): 757. CrossRef

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Cyclin D1 Overexpression, p16 Loss, and pRb Inactivation Play a Key Role in Pulmonary Carcinogenesis and have a Prognostic Implication for the Long-term Survival in Non-small Cell Lung Carcinoma Patients: Na-Hye Myong; Cancer Res Treat. 2008;40(2):45-52. Published online June 30, 2008; DOI: https://doi.org/10.4143/crt.2008.40.2.45

Abstract PDF PubReader ePub

Purpose

We investigated the immunoexpressions of cyclin D1, cyclin-dependent kinase inhibitor p16 and phosphorylated retinoblastoma (p-pRb) proteins in non-small cell lung carcinoma (NSCLC) to demonstrate their key roles in tumorigenesis, their relationship with the clinicopathologic factors, and their prognostic influences on the long-term survival.

Materials and Methods

115 surgically resected NSCLCs were immunohistochemically stained for the G₁/S cell cycle proteins, with using a tissue microarray. The correlation between their immunoexpressions and the clinicopathologic prognostic factors, their inter-relationships and their single or combined effects on the long-term survival (over 5 years) were statistically analyzed by SPSS15.0.

Results

Loss of p16 was found in 75% of the cases and cyclin D1 overexpression and phosphorylated pRb (p-pRb) were found in 64% and 46%, respectively. Cyclin D1 overexpression was correlated with the p16 loss and pRb inactivation by phosphorylation. The p16 loss was tightly associated with p-pRb. The Kaplan-Meier survival curves disclosed that the cyclin D1-positive group and the p16-negative group showed a rapid decline of survival at the point of about 5 years after surgery and thereafter. The combined actions of cyclin D1 overexpression, loss of p16 and pRb inactivation tended to have an adverse influence on the prolonged survival.

Conclusions

The observation that cyclin D1 overexpression, p16 loss and pRb inactivation were largely found in NSCLCs suggests that they play an important role in pulmonary carcinogenesis. Also, their inverse or positive correlations indicate that the G₁/S cell cycle proteins may act alternatively or synergistically on the mechanisms by which tumor cells escape the G₁ restriction point. Finally, their solitary or combined actions might have a long-term effect on the survival.

Citations

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Experimental and Therapeutic Medicine.2021;[Epub] CrossRef
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Cancers.2021; 13(21): 5486. CrossRef
Ultrasound-Targeted Microbubble Destruction Mediated si-CyclinD1 Inhibits the Development of Hepatocellular Carcinoma via Suppression of PI3K/AKT Signaling Pathway

Wei Yan, Li Cheng, Dongmei Zhang
Cancer Management and Research.2020; Volume 12: 10829. CrossRef
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