Microsatellite Instability in Invasive Ductal Carcinomas

Duck Hyoun Jeong; Jin Cheol Jeong; Chan Heun Park; Mi Jung Kwon; Seong Jin Cho; Eun Sook Nam; Hyung Sik Shin; Kwan Seok Kim

doi:10.4048/jbc.2007.10.1.77

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Jeong, Jeong, Park, Kwon, Cho, Nam, Shin, and Kim: Microsatellite Instability in Invasive Ductal Carcinomas

Original Article

Journal of Breast Cancer

Journal of Breast Cancer 2007; 10(1): 77-84.

Published online: 31 March 2007

DOI: https://doi.org/10.4048/jbc.2007.10.1.77

Microsatellite Instability in Invasive Ductal Carcinomas

Duck Hyoun Jeong, Jin Cheol Jeong, Chan Heun Park, Mi Jung Kwon¹, Seong Jin Cho¹, Eun Sook Nam¹, Hyung Sik Shin¹, Kwan Seok Kim²

Department of Surgery, Hallym University College of Medicine, Seoul, Korea.

¹Department of Pathology, Hallym University College of Medicine, Seoul, Korea.

²Dr. Kim's Clinic, Seoul, Korea.

hhh@hallym.or.kr

Received 24 January 2007 Accepted 7 March 2007

Abstract

Purpose

Breast cancer shows various molecular and genetic alterations in its development and progression. Microsatellite alterations, and especially microsatellite instability (MSI) and loss of heterozygosity (LOH), have recently been postulated as a novel mechanism of carcinogenesis and as a useful prognostic factor for several gastrointestinal malignancies. LOH is related to the allelic loss of various tumor suppressor genes; however, MSI has been found to be the result of an erroneous DNA mismatch repair system and this has been known to be involved in the carcinogenesis of the hereditary non-polyposis colon cancers and some portion of the sporadic colorectal or gastric cancers. Yet MSI has rarely been studied in invasive ductal carcinoma. Our objectives were to evaluate the MSI and p53 protein expression in invasive ductal carcinomas and to correlate this with various clinicopathological factors.

Methods

The MSI analysis was performed by using polymerase chain reaction with five polymorphic microsatellite markers (the BAT25, BAT26, D2S123, D5S346 and D17S250 loci as recommended by the 1998 NCI International Workshop on Microsatellite Instabilitis and RER phenotypes) in 50 surgically resected tumors and each of their non-tumorous counterpart. The p53 protein expression was studied using immunohistochemistry.

Results

MSI and a p53 protein expression were detected in 22% and 54% of the tumors and non-tumorous tissues, respectively. MSI was more frequently detected in tumor grade I, T-stage I, non-metastatic tumor and tumor stage I. Also there were rare cases showing a high grade and stage with metastasis in the MSI-high group, in which more than 3 microsatellite loci had MSI. The p53 expression results correlated well with a higher tumor grade. Correlation between MSI and the p53 expression was not found.

Conclusion

These results may suggest that MSI may be involved in some portions in mammary carcinogenesis and tumor invasion. Also the clinical use of the MSI status may help to determine a better prognosis among invasive ductal cancer patients.

Keywords: Invasive ductal carcinoma, p53, MSI, Immunohistochemistry

Figures and Tables

Fig 1

Representative MSI pattern of BAT25 (left) and D17S250 (right) markers in invasive ductal carcinoma. Each T lane shows mid-lower band gain.

N=normal; T=Tumor.

Fig 2

On immunohistochemical stain for p53, the tumor cells of invasive ductal carcinoma show strong nuclear expression.

Table 1

DNA sequences of 5 microsatellites in MSI study

Table 2

Clinicopathologic findings of 50 invasive ductal carcinomas

Table 3

p53 protein expression and MSI detection rate according to the clinicopathological factors (%)

MSI=microsatellite instability; LN=lymph node.

Table 4

Correlation between MSI & p53 protein expression

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