Cancer Res Treat.  2010 Sep;42(3):144-150.

Prognostic Role of Rb, p16, Cyclin D1 Proteins in Soft Tissue Sarcomas

Affiliations
  • 1Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea School of Medicine, Suwon, Korea.
  • 2Department of Pathology, St. Vincent's Hospital, The Catholic University of Korea School of Medicine, Suwon, Korea.
  • 3Department of Pathology, Seoul St. Mary's Hospital, The Catholic University of Korea School of Medicine, Seoul, Korea.
  • 4Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea School of Medicine, Seoul, Korea. jinkang@catholic.ac.kr

Abstract

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.

Keyword

Sarcoma; Retinoblastoma protein; p16 protein; Cyclin D1

MeSH Terms

Cyclin D1
Cyclins
Genes, Retinoblastoma
Humans
Immunochemistry
Multivariate Analysis
Odds Ratio
Proteins
Retinoblastoma Protein
Sarcoma
Survival Rate
X-Ray Film
Cyclin D1
Cyclins
Proteins
Retinoblastoma Protein

Figure

  • Fig. 1 Immunohistochemical staining of Rb, (A) p16, (B) cyclin D1, (C) in soft tissue sarcoma, which shows strong positive reaction in most of their nuclei (×400).

  • Fig. 2 (A) Overall survival curve. (B) Kaplan-Meier survival curve according to the expression level of Rb protein.


Reference

1. Enzinger FM, Weiss SW. Soft tissue tumors. 1995. 3rd ed. St. Louis: Mosby.
2. Li XQ, Parkekh SG, Rosenberg AE, Mankin HJ. Assessing prognosis for high-grade soft-tissue sarcomas: search for a marker. Ann Surg Oncol. 1996; 3:550–557. PMID: 8915487.
Article
3. Yao J, Pollock RE, Lang A, Tan M, Pisters PW, Goodrich D, et al. Infrequent mutation of the p16/MTS1 gene and overexpression of cyclin-dependent kinase 4 in human primary soft-tissue sarcoma. Clin Cancer Res. 1998; 4:1065–1070. PMID: 9563903.
4. Karpeh MS, Brennan MF, Cance WG, Woodruff JM, Pollack D, Casper ES, et al. Altered patterns of retinoblastoma gene product expression in adult soft-tissue sarcomas. Br J Cancer. 1995; 72:986–991. PMID: 7547254.
Article
5. Kim SH, Lewis JJ, Brennan MF, Woodruff JM, Dudas M, Cordon-Cardo C. Overexpression of cyclin D1 is associated with poor prognosis in extremity soft-tissue sarcomas. Clin Cancer Res. 1998; 4:2377–2382. PMID: 9796968.
6. Meye A, Würl P, Hinze R, Berger D, Bache M, Schmidt H, et al. No p16INK4A/CDKN2/MTS1 mutations independent of p53 status in soft tissue sarcomas. J Pathol. 1998; 184:14–17. PMID: 9582521.
Article
7. Coindre JM, Trojani M, Contesso G, David M, Rouesse J, Bui NB, et al. Reproducibility of a histopathologic grading system for adult soft tissue sarcoma. Cancer. 1986; 58:306–309. PMID: 3719523.
Article
8. Brambilla E, Moro D, Gazzeri S, Brambilla C. Alterations of expression of Rb, p16(INK4A) and cyclin D1 in non-small cell lung carcinoma and their clinical significance. J Pathol. 1999; 188:351–360. PMID: 10440744.
Article
9. Huang CI, Taki T, Higashiyama M, Kohno N, Miyake M. p16 protein expression is associated with a poor prognosis in squamous cell carcinoma of the lung. Br J Cancer. 2000; 82:374–380. PMID: 10646891.
Article
10. Kawabuchi B, Moriyama S, Hironaka M, Fujii T, Koike M, Moriyama H, et al. p16 inactivation in small-sized lung adenocarcinoma: its association with poor prognosis. Int J Cancer. 1999; 84:49–53. PMID: 9988232.
Article
11. Hommura F, Dosaka-Akita H, Kinoshita I, Mishina T, Hiroumi H, Ogura S, et al. Predictive value of expression of p16INK4A, retinoblastoma and p53 proteins for the prognosis of non-small-cell lung cancers. Br J Cancer. 1999; 81:696–701. PMID: 10574258.
Article
12. Kusume T, Tsuda H, Kawabata M, Inoue T, Umesaki N, Suzuki T, et al. The p16-cyclin D1/CDK4-pRb pathway and clinical outcome in epithelial ovarian cancer. Clin Cancer Res. 1999; 5:4152–4157. PMID: 10632354.
13. Salvesen HB, Das S, Akslen LA. Loss of nuclear p16 protein expression is not associated with promoter methylation but defines a subgroup of aggressive endometrial carcinomas with poor prognosis. Clin Cancer Res. 2000; 6:153–159. PMID: 10656444.
14. Takeuchi H, Ozawa S, Ando N, Shih CH, Koyanagi K, Ueda M, et al. Altered p16/MTS1/CDKN2 and cyclin D1/PRAD-1 gene expression is associated with the prognosis of squamous cell carcinoma of the esophagus. Clin Cancer Res. 1997; 3:2229–2236. PMID: 9815619.
15. Cohen JA, Geradts J. Loss of RB and MTS1/CDKN2 (p16) expression in human sarcomas. Hum Pathol. 1997; 28:893–898. PMID: 9269824.
Article
16. Kim SH, Cho NH, Tallini G, Dudas M, Lewis JJ, Cordon-Cardo C. Prognostic role of cyclin D1 in retroperitoneal sarcomas. Cancer. 2001; 91:428–434. PMID: 11180091.
Article
17. Wurl P, Meye A, Lautenschläger C, Schmidt H, Bache M, Kalthoff H, et al. Clinical relevance of pRb and p53 co-overexpression in soft tissue sarcomas. Cancer Lett. 1999; 139:159–165. PMID: 10395173.
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