Published online Dec 31, 2006.
https://doi.org/10.4048/jbc.2006.9.4.309
Loss of Heterozygosity of Chromosome 17p13 and p53 Expression in Invasive Ductal Carcinomas
Abstract
Purpose
The p53 gene is located on chromosome 17p13 and may play important roles in cell cycle regulation, apoptosis and the regulation of the expression of other genes as well as tumor suppression. In addition, the p53 gene is believed to play an important role in the progression of various human malignant tumors through mutation and overexpression. There have been few studies on loss of heterozygosity (LOH) study on 17p13 in invasive ductal carcinoma. This study evaluated a 17p13 LOH and protein expression in invasive ductal carcinomas and correlated these results with the clinicopathological factors.
Methods
LOH analysis was carried out using a polymerase chain reaction with four polymorphic microsatellite markers (D17S796, TP53, D17S5, D17S513) in 50 surgically resected tumors and their non-tumorous counterparts. The p53 protein expression level was examined using immunohistochemistry.
Results
A LOH and protein expression was detected in 66% and 54% of the tumors, respectively. The LOH rates ranged from 26.3% (D17S513) to 33.3% (TP53). There was no detected LOH or protein expression in the non-tumor parts. The LOH results correlate well with the tumor size and stage. The protein expression results correlate well with the tumor histological grade. There was no correlation between the LOH and protein loss.
Conclusion
17p13 LOH and p53 gene abnormalities may be associated with tumorigenesis and tumor invasion. In addition, the combined use of both methods may help in early detection as well as for determining the prognosis of an invasive ductal carcinoma. 17p13 LOH and p53 protein expression may contribute to tumor progression through reciprocal complementation in some portions of the invasive ductal carcinoma.
Fig 1
LOH at chromosome 17p13 loci in invasive ductal carcinoma. Representative D17S513 (left) and D17S5 microsatellite analysis of N (normal) and T (Tumor). Each T lane shows lower band loss (left) and considerable band loss (right).
Fig 2
Immunohistochemically, the tumor cells of invasive ductal carcinoma show strong nuclear expression.
Table 1
DNA sequences of 4 microsatellites on 17p13
Table 2
Clinicopathologic findings of 50 invasive ductal carcinomas.
Table 3
17p13 LOH and p53 protein expression according to the clinicopathological factors
Table 4
Correlation between LOH & Protein Expression
References
-
2002 Annual Report of the Central Cancer Registry in Korea. Republic of Korea: Ministry of Health and Welfare; 2003. pp. 11.
-
-
Calderon-Margalit R, Paltiel O. Prevention of breast cancer in women who carry BRCA1 or BRCA2 mutations: a critical review of the literature. Int J Cancer 2004;10:357–364.
-
-
Vousden KH, Prives C. P53 and prognosis: new insights and further complexity. Cell 2005;14:7–10.
-
-
Park JH, Kim SJ, Choi UJ, Lee KM. Correlation of the Immunohistochemical Coexpression of p53 and HER-2/neu and the Prognosis of Breast Cancer. J Breast Cancer 2005;8:41–47.
-
-
Jo HJ, Yun KJ, Moon HB. Expression of p21, p53 and bcl-2 Proteins in Invasive Ductal Carcinoma of the Breast. Korean J Pathol 2003;37:393–399.
-
-
Kim JK, Song YJ, Cho SI, Ryu DH, Yun HY, Sung RH. Clinicopathologic Significance of p53 and c-erbB-2 Protein Expression in Breast Carcinoma. J Korean Surg Soc 2002;62:282–287.
-
-
Roncuzzi L, Brognara I, Baiocchi D, Amadori D, Gasperi-Campani A. Loss of heterozygosity at 17p13.3-ter, distal to TP53, correlates with negative hormonal phenotype in sporadic breast cancer. Oncol Rep 2005;14:471–474.
-
-
Suh KS, Lee YH, Na SY, Park MI, Kim HS, Lee SK. Mutational and Loss of Heterozygosity Analysis of the p53 and PTEN Tumor Suppressor Genes in Breast Carcinoma. Korean J Pathol 2005;39:313–319.
-