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Expression of Cluster of differentiation 44 (CD44) according to Clinicopathologic Characteristics of Gastric Cancer

Title
Expression of Cluster of differentiation 44 (CD44) according to Clinicopathologic Characteristics of Gastric Cancer
Other Titles
위암의 임상적 특징에 따른 Cluster of differentiation 44 (CD44)의 발현
Authors
류민선
Issue Date
2018
Department/Major
대학원 의학과
Publisher
이화여자대학교 대학원
Degree
Doctor
Advisors
정성애

문창모
Abstract
연구배경: 암 줄기세포는 자기 재생이 가능하고 다른 표현형으로 분화할 수 있는 능력을 가진 종양 내 존재하는 세포 군집으로 정의된다. 분화클러스터 44 (CD44) 는 위암 줄기세포 마커의 하나로, 본 연구에서는 위암 환자들의 임상적 특징에 따라 CD44 발현의 차이가 있는지 분석하고 CD44를 발현하는 위암 환자에서 예후 차이에 대해 알아보고자 하였다. 연구방법: 1998년 5월부터 2009년 12월까지 이화여자대학교 부속병원에서 위암으로 수술받은 환자 157명을 무작위로 선별하였다. 절제된 조직 슬라이드에 CD44 면역화학염색을 하였고 반정량적인 방법으로 강도와 분율의 점수를 매겼다. 강도와 뷴율의 점수 합이 3점 이상인 경우를 CD44 양성으로 판정하였다. 연구결과: 143명의 환자 중 CD44 양성인 환자는 69명 (48.3%) 였다. CD44는 장형 위암에서 통계적으로 유의하게 발현되었고 (P = 0.038), 60세 이상, 림프관 침윤이 있는 경우, 림프절 전이가 있는 경우 역시 CD44 발현과 관계가 있었다. 위암의 발생 위치에 따른 CD44 발현의 차이는 없었다. 다변량분석에서 나이 (60세 이상) 만이 CD44 발현과 연관된 독립적인 인자로 나타났다 (P = 0.028). 전체생존율은 CD44 양성인 위암 환자에서 CD44 음성인 환자에 비해 유의하게 낮았다 (P = 0.006). 5년생존율과 무병생존율 역시 CD44 발현과 유의한 관계가 있었다. 다변량분석에서 전체생존율과 관련된 독립적인 인자는 나이 (60세 이상), 남성, 림프관 침윤이었고, 5년생존율과 관련된 독립적인 인자는 나이 (60세 이상), 림프관 침윤이었으며, 무병생존율과 관계된 독립적인 인자는 림프관 침윤이었다. 결론: CD44는 장형 위암에서 발현되는 경향을 보이며, 림프관 침윤, 림프절 전이와 관련된다. 또한, 위암의 나쁜 예후인자로 생각된다.;Background/Aims: Cancer stem cells (CSCs) are defined as focal cluster of cells within tumor that possess the capacity for self-renewal and differentiating into phenotypically heterogeneous. Cluster of differentiation 44 (CD44) was considered as one of the gastric CSC marker. We aimed to investigate how different the expression of CD44 according to the clinicopathologic characteristics in gastric cancer. Methods: From May 1998 to December 2009, 157 patients who were operated due to gastric cancer were selected. Immunohistochemical staining with anti-CD44 monoclonal antibody was performed on the sections of resected specimens. Immunohistochemistry of CD44 was reviewed by semi-quantitative scoring of intensity and proportion in the three hot spots. The sum of intensity and proportion scores was calculated. 2 or less of the score was evaluated as negative and 3 or more of the score as positive. Results: Among 143 subjects, sixty-nine patients (48.3%) were CD44 positive. Expression of CD44 was significantly higher in intestinal type gastric cancer (P = 0.038). Also, older age (≥ 60 years), lymphatic invasion, and lymph node metastasis were significantly correlated with expression of CD44. There was no significant difference in CD44 expression according to the location of gastric cancer. By multivariate analysis, older age (≥ 60 years) was the only independent factor associated with CD44 expression (P = 0.028). The overall survival was significantly worse in CD44 positive patients compared to CD44 negative patients (P = 0.006). CD44 expression was also correlated with 5-year survival and disease-free survival (P = 0.005 and P = 0.043). By multivariate analysis with Cox regression model, older age (≥ 60 years), male and lymphatic invasion were independent predictors for poor overall survival (P = 0.007, P = 0.035, and P = 0.003, respectively). Also, older age (≥ 60 years) and lymphatic invasion were significant factors for 5-year survival by multivariate analysis (P = 0.011 and P = 0.005) and lymphatic invasion was an independent factor of poor disease-free survival (P = 0.002). Conclusion: CD44 expression is higher in the intestinal type gastric cancer and correlated with older age, lymphatic invasion, and lymph node metastasis. Also, CD44 expression is predictive of poor prognosis in gastric cancer.
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