Cyclin D₁ Overexpression and Prognosis in Colorectal Adenocarcinoma

Abstract

Recently, it has been reported that cyclin D₁ plays a major role in oncogenesis in various cancers; however, there have been few studies on the association of cyclin D₁ overexpression and prognosis of patients with malignant tumors. We evaluated the prognostic significance of cyclin D₁ overexpression in colorectal adenocarcinoma. One hundred twenty-three specimens resected from patients with colorectal adenocarcinomas were investigated by staining with a monoclonal antibody against cyclin D₁. As a result, both overall survival and disease-free survival were significantly poorer in the patients with tumors strongly positive for cyclin D₁ than in those with cyclin-D₁-negative or weakly positive tumors. The 5-year survival rate of the patients with tumors strongly positive for cyclin D₁ was 53.3%, while the 5-year survival rates of patients with cyclin-D₁-negative and weakly positive tumors were 96.2 and 78.8%, respectively. Moreover, multivariate analysis indicated that cyclin D₁ overexpression is an independent predictor of disease recurrence in our patients. In conclusion, cyclin D₁ overexpression may be useful as a predictor of disease recurrence in colorectal adenocarcinoma.

Expression of cyclins A and D and p21(waf1/cip1) proteins in renal cell cancer and their relation to clinicopathological variables and patient survival

“…However, the results are variable, since the close relationship between overexpression of cyclin D1 and malignant cellular prognostic features has been observed in other cancers (Nakamura et al, 1997;Pignataro et al, 1998). In gastric and colon cancer the strong expression of cyclin D1 is related to lymph node involvement (Nakamura et al, 1997;Maeda et al, 1998), and in ovarian cancer to tumour malignancy (Barbieri et al, 1997). In addition, our analysis revealed a positive correlation (Table 2) between the expression of p21 (waf1/cip1) and cyclin D1.…”

“…The overexpression of cyclins has been related to high proliferation rate of the tumour cells and to other unfavourable prognostic factors, although the results are not uniform (Aaltomaa et al, 1999a;Donnellan and Chetty, 1998;Ishikawa et al, 1998;Maeda et al, 1998;Volm et al, 1998). The gene amplification and protein expressions of cyclins A and D1 have been previously studied in several human epithelial neoplasms to establish their possible prognostic significance in clinical human cancer (Barbareschi et al, 1997;Michalides et al, 1997;Aaltomaa et al, 1999a;Donnellan and Chetty, 1998;Maeda et al, 1998;Volm et al, 1998). At present there are no reports available on the prognostic value of the expressions of cyclins A and D1 in RCC.…”

Functional domains in cyclin D1: pRb-kinase activity is not essential for transformation

“…Subsequently it has been found in a more common rearrangement [the t(14 : 11) translocation] which plays a role in B-cell lymphomas (BCL1) (Rosenberg et al, 1991b(Rosenberg et al, , 1993Motokura and Arnold, 1993). Cyclin D1 is also ampli®ed and overexpressed in a number of breast and prostate tumours, colon adenocarcinomas and squamous cell carcinomas of the head and neck (Lammie and Peters, 1991;Buckley et al, 1993;Tam et al, 1994, Han et al, 1998, Maeda et al, 1998. This circumstantial evidence for the involvement of cyclin D1 in oncogenesis was substantiated when it was shown that cyclin D1 cooperates with Myc family members in the induction of tumours in transgenic mice (Bodrug et al, 1994;Lovec et al, 1994a;Wang et al, 1994) and with Ha-ras in the transformation of cultured cells (Hinds et al, 1994;Lovec et al, 1994b).…”

Expressão de Ciclina D1 em Carcinoma de Células Renais

“…Seria lógico presumir então que alta expressão intratumoral de Ciclina D1 estaria relacionada a uma maior capacidade para metástase e ocorrência precoce de micrometástases do que tumores onde expressão da proteína é baixa. Em estudos envolvendo carcinoma papilífero da tireóide e adenocarcinoma colorretal, verificou-se uma relação entre forte expressão de Ciclina D1 e metástase para linfonodos (MAEDA;CHUNG et al, 1998;PALLA et al, 2010). Em nosso estudo, no entanto, não foi o que observamos.…”

“…Além disso, alta expressão da proteína estava associada a um pior prognóstico nos estágios iniciais (I, II) do carcinoma de pulmão não pequenas células, mesmo após análise multivariada (ZHU; YU et al, 2010). Maeda et al, 1998, analisando uma amostra de 123 tumores de pacientes com adenocarcinoma colorretal, também verificaram menor sobrevida, além de maior taxa de recorrência, entre os pacientes contendo tumores com Ciclina D1 alta (MAEDA;CHUNG et al, 1998).…”