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MLH1과 MSH2 단백발현 소실을 보이는 산발성 대장암의 임상병리학적 특징 - 낮은 전이 가능성

Clinicopathologic Features of Sporadic Colorectal Cancer with MLH1/MSH2 Loss of Expression - Reduced Likelihood of Metastases

대한대장항문학회지 2008년 24권 3호 p.175 ~ 183
박지원 ( Park Ji-Won ) - 국립암센터 대장암센터

장희진 ( Chang Hee-Jin ) - 국립암센터 대장암센터
정경해 ( Jung Kyung-Hae ) - 국립암센터 대장암센터
김대용 ( Kim Dae-Yong ) - 국립암센터 대장암센터
손대경 ( Sohn Dae-Kyung ) - 국립암센터 대장암센터
한경수 ( Han Kyung-Soo ) - 국립암센터 대장암센터
홍창원 ( Hong Chang-Won ) - 국립암센터 대장암센터
임석병 ( Lim Seok-Byung ) - 국립암센터 대장암센터
최효성 ( Choi Hyo-Seong ) - 국립암센터 대장암센터
정승용 ( Jeong Seung-Yong ) - 국립암센터 대장암센터
이상전 ( Lee Sang-Jeon ) - 충북대학교 의과대학 외과학교실

Abstract


Purpose: This study was designed to determine the frequency of MMR defective sporadic colorectal cancer (CRC) by using immunohistochemistry and to investigate the correlation between the MMR status and the metastatic potential.

Methods: The study included 249 patients with sporadic colorectal cancer who underwent surgical resection. The MMR status was determined by using an immunohistochemical analysis of MLH1 and MSH2 expression.

Results: Twenty seven (10.8%) carcinomas showed abnormal MMR protein expression (18 MLH1 negative and 9 MSH2 negative) and were classified as MMR defective tumors whereas 222 tumors demonstrated normal MLH1/MSH2 immunoreactivity (MMR intact tumor). MMR defective tumors developed at significantly higher frequencies in a proximal site (59.3% vs. 27.5%, P=0.001) and tended to be larger in size (6.3±2.4 cm vs. 5.1±2.1 cm, P=0.026). They showed significantly lower overall stage, N stage, and M stage at the time of diagnosis (P=0.002, P=0.014, P=0.010, respectively). In patients who had MMR defective tumors, lymphocytic infiltration (40.7% vs. 8.7%, P<0.001) and poor differentiation (22.2% vs. 11.7%, P=0.012) were more frequently observed. Less frequently MMR defective tumors displayed lymphatic invasion (40.7% vs. 67.1%, P=0.007) and infiltrative borders (22.2% vs. 51.8%, P=0.004). The MMR defect was strongly associated with a decreased likelihood of lymph node (odds ratio: 0.34, 95% CI: 0.13∼0.95) and distant organ metastases at diagnosis (odds ratio: 0.09, 95% CI: 0.01∼0.94), independent of the clinicopathologic features.

Conclusions: Immunohistochemical analysis revealed that 10.8% of sporadic CRC cases showed no staining for MLH1 or MSH2. Lymphatic invasion and distant metastases were found at lower rates in these MMR defective tumors. J Korean Soc Coloproctol 2008;24:175-183

키워드

산발성 대장암;복제오류교정단백;미소위성체 불안정성;면역조직화학염색
Sporadic colorectal cancer;Mismatch repair protein;Microsatellite instability;Immunohistochemistry
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