Expression of Cyclins A and D and P21(waf1/cip1) Proteins in Renal Cell Cancer and Their Relation to Clinicopathological Variables and Patient Survival

Overview

Journal Br J Cancer

Specialty Oncology

Date 1999 Sep 2

PMID 10471053

Citations 20

Authors

S Aaltomaa

P Lipponen

M Ala-Opas

M Eskelinen

K Syrjanen

V M Kosma

Affiliations

Soon will be listed here.

Abstract

We have studied 118 renal cell carcinomas to analyse the expressions of cyclins A and D1 and p21(waf1/cip1), and their relationship to clinical and histopathological parameters as well as to clinical outcome. Cyclins A and D1 and cyclin-dependent kinase inhibitor p21 (waf1/cip1) were not expressed in normal renal tissue. Staining signals of cyclin D1 and p21(waf1/cip1) were always nuclear but cyclin A was also expressed in the cytoplasm of the tumour cells. The mean (range) fractions of cyclin A, cyclin D1 and p21(waf1/cip1)-positive tumour cells were 2.2% (range 0-20%), 23.3% (range 0-90%) and 6.8% (range 0-70%) respectively. The expression of cyclin A was related to venous invasion, high nuclear grade, high mitotic rate, high Ki-67 and high PCNA expressions (P < or = 0.006 for all). The expression of cyclin D1 was linked with age over 65 years, low nuclear grade and high p53 expression (P < or = 0.05 for all). An inverse correlation was present between p21(waf1/cip1) and cyclin D1 (P = 0.011). Cyclin A predicted survival in the entire study group (P = 0.0014), in T1-4/N0-2/M0 (P = 0.0007) and in T1-2/N0/M0 tumours (P = 0.0007). Cyclin A was also a powerful predictor of disease-free survival in T1-4/N0/M0 (P = 0.0027) tumours (P = 0.0007). Cyclin D1 and p21(waf1/cip1) were not significantly related to survival or disease-free survival in any of the groups. In the entire material the independent prognostic factors were the presence of distant metastases (relative risk (RR) 5.16, P < 0.001), T category (RR 2.68, P < 0.001), Ki-67 expression (RR 1.02, P = 0.026) and cyclin A expression (RR 1.12, P = 0.001). The independent predictors in T1-4/N0/M0 tumours were T-category (RR 2.67, P = 0.001) and cyclin A (RR 1.21, P < 0.001), and in T1-2/N0/M0 tumours the only significant predictor was cyclin A (RR 1.19, P = 0.0002). In renal cell carcinoma, cyclin A is a powerful and independent prognostic factor in all clinical stages of the disease, whereas cyclin D1 and p21(waf1/cip1) have no prognostic value.

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References

Paul R, Ewing C, Robinson J, Marshall F, Johnson K, Wheelock M . Cadherin-6, a cell adhesion molecule specifically expressed in the proximal renal tubule and renal cell carcinoma. Cancer Res. 1997; 57(13):2741-8. View

Shin K, Kong G, Kim W, Lee T, Woo Y, Lee J . Overexpression of cyclin D1 correlates with early recurrence in superficial bladder cancers. Br J Cancer. 1997; 75(12):1788-92. PMC: 2223624. DOI: 10.1038/bjc.1997.305. View

Yasui W, Akama Y, Yokozaki H, Semba S, Kudo Y, Shimamoto F . Expression of p21WAF1/CIP1 in colorectal adenomas and adenocarcinomas and its correlation with p53 protein expression. Pathol Int. 1997; 47(7):470-7. DOI: 10.1111/j.1440-1827.1997.tb04526.x. View

Hofmockel G, Bassukas I, Wittmann A, Dammrich J . Is the expression of multidrug resistance gene product a prognostic indicator for the clinical outcome of patients with renal cancer?. Br J Urol. 1997; 80(1):11-7. DOI: 10.1046/j.1464-410x.1997.00228.x. View

Nakamura M, Katano M, Fujimoto K, Morisaki T . A new prognostic strategy for gastric carcinoma: mRNA expression of tumor growth-related factors in endoscopic biopsy specimens. Ann Surg. 1997; 226(1):35-42. PMC: 1190904. DOI: 10.1097/00000658-199707000-00005. View

Papadopoulos I, Rudolph P, Weichert-Jacobsen K . Value of p53 expression, cellular proliferation, and DNA content as prognostic indicators in renal cell carcinoma. Eur Urol. 1997; 32(1):110-7. View

Backe J, Gassel A, Hauber K, Krebs S, Bartek J, Caffier H . p53 protein in endometrial cancer is related to proliferative activity and prognosis but not to expression of p21 protein. Int J Gynecol Pathol. 1998; 16(4):361-8. DOI: 10.1097/00004347-199710000-00011. View

Ishikawa T, Furihata M, Ohtsuki Y, Murakami H, Inoue A, Ogoshi S . Cyclin D1 overexpression related to retinoblastoma protein expression as a prognostic marker in human oesophageal squamous cell carcinoma. Br J Cancer. 1998; 77(1):92-7. PMC: 2151245. DOI: 10.1038/bjc.1998.14. View

Maeda K, Chung Y, Kang S, Ogawa M, Onoda N, Nishiguchi Y . Cyclin D1 overexpression and prognosis in colorectal adenocarcinoma. Oncology. 1998; 55(2):145-51. DOI: 10.1159/000011849. View

10.

Naka T, Toyota N, Kaneko T, Kaibara N . Protein expression of p53, p21WAF1, and Rb as prognostic indicators in patients with surgically treated hepatocellular carcinoma. Anticancer Res. 1998; 18(1B):555-64. View

11.

Donnellan R, Chetty R . Cyclin D1 and human neoplasia. Mol Pathol. 1998; 51(1):1-7. PMC: 395600. DOI: 10.1136/mp.51.1.1. View

12.

Volm M, Koomagi R, Rittgen W . Clinical implications of cyclins, cyclin-dependent kinases, RB and E2F1 in squamous-cell lung carcinoma. Int J Cancer. 1998; 79(3):294-9. DOI: 10.1002/(sici)1097-0215(19980619)79:3<294::aid-ijc15>3.0.co;2-8. View

13.

Lipponen P, Aaltomaa S, Eskelinen M, Ala-Opas M, Kosma V . Expression of p21(waf1/cip1) protein in transitional cell bladder tumours and its prognostic value. Eur Urol. 1998; 34(3):237-43. DOI: 10.1159/000019721. View

14.

Pignataro L, Pruneri G, Carboni N, Capaccio P, Cesana B, Neri A . Clinical relevance of cyclin D1 protein overexpression in laryngeal squamous cell carcinoma. J Clin Oncol. 1998; 16(9):3069-77. DOI: 10.1200/JCO.1998.16.9.3069. View

15.

Aaltomaa S, Eskelinen M, Lipponen P . Expression of cyclin A and D proteins in prostate cancer and their relation to clinopathological variables and patient survival. Prostate. 1999; 38(3):175-82. DOI: 10.1002/(sici)1097-0045(19990215)38:3<175::aid-pros1>3.0.co;2-#. View

16.

Aaltomaa S, Lipponen P, Eskelinen M, Ala-Opas M, Kosma V . Prognostic value and expression of p21(waf1/cip1) protein in prostate cancer. Prostate. 1999; 39(1):8-15. DOI: 10.1002/(sici)1097-0045(19990401)39:1<8::aid-pros2>3.0.co;2-n. View

17.

Syrjanen K, HJELT L . Grading of human renal adenocarcinoma. Scand J Urol Nephrol. 1978; 12(1):49-55. View

18.

Haapasalo H, Pesonen E, Collan Y . Volume corrected mitotic index (M/V-INDEX). The standard of mitotic activity in neoplasms. Pathol Res Pract. 1989; 185(5):551-4. DOI: 10.1016/S0344-0338(89)80191-8. View

19.

Lipponen P, Eskelinen M, Hietala K, Syrjanen K, Gambetta R . Expression of proliferating cell nuclear antigen (PC10), p53 protein and c-erbB-2 in renal adenocarcinoma. Int J Cancer. 1994; 57(2):275-80. DOI: 10.1002/ijc.2910570224. View

20.

Waga S, Hannon G, Beach D, Stillman B . The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA. Nature. 1994; 369(6481):574-8. DOI: 10.1038/369574a0. View