Overexpression of cyclin D1 is associated with poor prognosis in extremity soft-tissue sarcomas.

نویسندگان

  • S H Kim
  • J J Lewis
  • M F Brennan
  • J M Woodruff
  • M Dudas
  • C Cordon-Cardo
چکیده

Binding of G1 cyclins to cyclin-dependent kinases leads to phosphorylation of the retinoblastoma protein and progression through G1 and S phases of the cell cycle. Overexpression of cyclins is thought to deregulate this process and has been noted in many human malignancies. This study was conducted to assess patterns of expression and potential gene amplification of the G1 cyclins in 84 patients affected with extremity soft-tissue sarcomas. Sixty cases were primary tumors, whereas the remaining 24 cases were locally recurrent lesions. There were 58 high-grade and 26 low-grade tumors. Immunohistochemical analyses were conducted using antibodies to cyclins D1, E, and A. Southern blot analysis was performed on DNA available from 53 of 84 patients with a cyclin D1-specific probe. Cyclin D1 overexpression was noted in 23 of 79 informative cases (29%), whereas cyclin E was found overexpressed in 26 of 80 cases (33%) and cyclin A overexpression was observed in 9 of 81 cases (11%). Overexpression of cyclins D1, E, or A each correlated significantly with high tumor grade (P <0.05). On multivariate analysis, neither cyclin E nor cyclin A were significant predictors of outcome. However, overexpression of cyclin D1 was significantly associated with worse overall survival for the entire group as well as in the subset of high-grade lesions (P <0.05), notwithstanding the relatively short follow-up time (mean, 2.4 years). Nevertheless, the presence of a significant association between laboratory data and outcome implies that the study is adequately powered. Furthermore, none of the cases demonstrated CCND1 gene amplification. These data support the concept that cyclin D1 overexpression determines the evolution of a particularly aggressive subset of these lesions.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Expression of SIRT1 and DBC1 Is Associated with Poor Prognosis of Soft Tissue Sarcomas

UNLABELLED Recently, the roles of SIRT1 and deleted in breast cancer 1 (DBC1) in human cancer have been extensively studied and it has been demonstrated that they are involved in many human carcinomas. However, their clinical significance for soft-tissue sarcomas has not been examined. In this study, we evaluated the expression and prognostic significance of the expression of SIRT1, DBC1, P53, ...

متن کامل

Altered expression of cell cycle regulatory proteins in benign and malignant bone and soft tissue neoplasms.

BACKGROUND The binding of cyclins to cyclin-dependent kinases regulates cell proliferation. Overexpression of cyclins is believed to deregulate the cell cycle in human tumors. Here the expression of G1 cyclins D1 and D3, and of Ki-67 in a variety of bone and soft tissue sarcomas was assessed as compared to adjacent normal tissue and to a subset of leiomyomas. MATERIALS AND METHODS Twenty-nine...

متن کامل

Overexpression of cyclin D1 in human pancreatic carcinoma is associated with poor prognosis.

We have investigated the expression of cyclin D1 in adenocarcinoma of the pancreas and the relevance of cyclin D1 expression to clinical outcome. In comparison to normal pancreas, Southern blot analyses revealed amplification of the cyclin D1 coding gene in 25% of the cases, whereas with reverse transcription-PCR, overexpression of mRNA was observed in 82% of the examined tissues. Immunohistoch...

متن کامل

P-96: Appositional Expressions of Cyclin D1 and E2F1 Gene Machineries in Mycooestrogen Zeralenone-Induced Apoptosis in Testicular Tissue of Rats

Background: Zearalenone (ZEA) is known as a nonsteroidal oestrogenic mycotoxin produced by different species of Fusarium fungi. ZEA is known for its competitive effects with the natural 17-β estradiol to bind with the specific binding sites of the estrogen receptors (Ers). On the other hand, the cyclin family (especially cyclin D1) and E2F1 genes are the checkpoint genes involved in cell cycle....

متن کامل

Longer Survival in Patients with Breast Cancer with Cyclin D1 Over-Expression after Tumor Recurrence: Longer, but Occupied with Disease

PURPOSE The effect of cyclin D1 overexpression on breast cancer outcomes and prognosis is controversial, even though amplification of the cyclin D1 gene, CCND1, has been shown to be associated with early relapse and poor prognosis. In this study, we examined the relationship between cyclin D1 overexpression and disease-specific survival (DSS). We also analyzed survival in patients who experienc...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Clinical cancer research : an official journal of the American Association for Cancer Research

دوره 4 10  شماره 

صفحات  -

تاریخ انتشار 1998