상피성 난소종양에서 SPARC 발현과 임상병리학적 연관성에 관한 연구
THE CLINICOPATHOLOGICAL RELEVANCE FOR THE EXPRESSION OF SECRETED PROTEIN ACIDIC AND RICH IN CYSTEINE IN EPITHELIAL OVARIAN TUMORS
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초록
목적Secreted protein acidic and rich in cysteine (SPARC)는 세포 부착과 운동, 세포 분화, 세포 증식, 그리고 혈관형성 등에 영향을 주는 기질세포 당단백이다. 이 물질은 다양한 암세포의 증식과 억제에 관련된 것으로 알려져 왔다. 본 연구의 목적은 난소상피종양 발생 및 진행에있어 SPARC 발현양상과 임상병리학적 인자들과의 상관관계를 알아보고자 한다. 연구방법수술 후 획득한 악성 상피성 난소종양 69예, 경계성 종양 18예, 양성종양 10예 그리고 정상 난소 조직을 대상으로 하였고, SPARC 단백의발현은 면역조직화학염색을 통하여 조사하였다. 후향적 분석을 통하여 환자의 성향과 표본을 분석하였다. 결과SPARC 면역조직화학염색에서 정상 난소 조직의 경우 거의 모든 조직에서 간질세포가 양성 소견을 보였으며, 일부 양성 및 경계성 종양조직에서도 양성 소견을 보였다(100%, 94.7%, and 100%). 반면 명확한 침윤을 보이는 상피성 난소암으로 진행할수록 간질세포에 대한SPARC 단백 발현은 의미 있게 감소하는 경향을 보였고(63.8% [44/69]), 면역반응 점수도 유의하게 감소되었다(P ＜ 0.001). 상피성 난소암에서의 SPARC의 발현은 International Federation of Gynecology and Obstetrics 병기와 유의한 상관관계가 있었다. 그러나 조직학적 유형,종양 분화도, 핵등급, 세포분열 수, 종양의 크기, 국소재발, 원격전이, 그리고 생존율 등의 다른 임상병리학적 인자들과는 유의한 상관관계를 보이지 않았다. 결론본 연구는 SPARC 단백 발현의 감소는 종양의 악성도와 유의하게 관련되어 있으며 SPARC는 상피종양 발생과정에 있어 종양억제 인자로서 작용함을 보여준다.
Abstract
Objective Secreted protein acidic and rich in cysteine (SPARC) is an extracellular matrix-associated protein implicated in the modulation of cell adhesion, migration, cell cycle regulation, and angiogenesis. It has been associated with the progression or suppression of various cancers. This study was aimed at correlating SPARC protein expression with tumor progression and clinicopathological features in ovarian epithelial tumors. Methods Epithelial ovarian cancer (n=69), borderline tumor (n=18), benign tumor (n=10) and normal ovary tissues were obtained after operation. SPARC protein expression was examined using immunohistochemistry. With a retrospective review, patients’characteristics and slide samples were analyzed. Results Cytoplasmic SPARC immunoreactivity was observed in stromal cells in nearly all cases of normal ovary, benign and borderline tumors (100%, 94.7%, and 100%). In contrast, SPARC was detected in the stroma of 63.8% (44/69) and the score of immunoreactivity was signifi cantly reduced in malignant tumors (P <0.001). SPARC expression in ovarian epithelial cancers was signifi cantly associated with International Federation of Gynecology and Obstetrics stage. However, it was not correlated with other clinicopathologic parameters, including histologic type, tumor grade, nuclear grade, mitosis, tumor size, local recurrence, distant metastasis, and survival. Conclusion This study showed that reduction of SPARC expression in ovarian epithelial tumors is significantly correlated with tumor invasiveness and SPARC may act as tumor suppressor.
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