DNA 현미 부수체 불안전성 특성을 가진 산발성 대장암의 임상병리학적 특징

Abstract

Purpose: Sporadic colorectal cancers, with DNA microsatellite instability (MSI), have been characterized by a predilection area of proximal colon, younger age onset, exophytic growth and larger tumor size. MSI colorectal cancers have recently been had a good survival rate. The aim of this study is to determine the MSI status in sporadic colorectal cancers, and compare their clinical and pathological characteristics with those of MSS (Microsatellite Stable) cancers.

Methods: Between March 1995 and December 1997, deep frozen fresh tissue of 107 eligible colorectal cancer patients, who underwent surgical resections, were used for analysis. Hereditary nonpolyposis colorectal cancer, and familial adenomatous polyposis, patients were excluded. All the patients were registered on a colorectal cancer database, and followed up completely with regular visits for a potential recurrence. Genomic DNA was prepared by the SDS-proteinase K and phenol chloroform extraction methods. The DNA was amplified by PCR at five microsatellite loci (BAT26, BAT25, D2S123, D5S346, and D17S250) to evaluate the MSI. The PCR products were separated in 6% polyacrylamide gels, containing 5.6 M urea, followed by autoradiography. The MSI was defined as being over 2 marker positive, and the MSS as 1 marker positive, all marker negatives were classed as MSS. The survival rates were calculated by the Kaplan-Meier methods.

Results: MSI was noted at 16/107 (15%), with mean ages for the patients of 51.8 vs. 58.6 years old for MSI and MSS, respectively. For the patients under 40 years old 5 (31.3%) vs. 6 (6.6%) had MSI and MSS, respectively (p＜0.01). The cancer was located in the right colon in 12 of each of the MSI and MSS (p＜0.01). There were no MSI rectal cancer tumors. The average tumor sizes were 7.6±3.6 ㎝ vs. 5.3±2.2 ㎝ (p＜0.01) for MSI and MSS, respectively, but there were no correlations with the frequency of associated polyps, recurrence and distant metastasis between MSI and MSS. The cells were well differentiated (12.5% vs. 17.6%), moderately differentiated (68.8% vs. 76.9%), poorly differentiated (6.2% vs. 3.3%), and mucinous type (12.5% vs. 2.2%), with MSI and MSS, respectively. The overall survival rates were 93.8% vs. 73.8% for MSI and MSS (P=0.07), respectively.

Conclusions: Sporadic colorectal cancer, with DNA microsatellite instability (MSI), was located predominantly in the proximal colon, in the younger age onset, and larger size of tumor. The survival rate of the patients with MSI tumors were good, but with no statistical significance.