자궁경부암의 진행과정에서 Thymidine Phosphorylase 발현과 조직학적 소견 및 신생혈관형성의상관관계에 대한 연구
Thymidine Phosphorylase Expression in Progression of Cervical Lesions: Histological Features and Microvessel Density
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목적: 상피 및 기질내에서의 티미딘 인산화제 (thymdine phosphorylase, 이하 TP)의 발현이 자궁경부암에서 혈관생성 및 종양성장에 어떻게 영향을 끼치는지 알아보고 여러 임상적 혹은 병리학적 예후 인자와의 관련성을 알아보고자 하였다. 연구 방법: 양성 자궁질환으로 전자궁적출술을 받은 경우 4예, 자궁경부 상피내암 (CIS) 9예, 미세침윤암 7예, 침윤암으로 진단받은 25예의 자궁 경부 조직 표본들을 대상으로 면역조직염색법을 시행하여 신생혈관 및 TP의 발현정도를 알아보았다. 결과: TP의 발현은 정상 자궁경부조직에서부터 자궁경부 상피내종양을 거쳐 침윤성 자궁경부암으로 진행함에 따라 증가하였다. 상피와 기질내에서 TP의 발현은 맥관형성과 밀접한 관계를 가졌다. 각 조직학적 상태에 따라 TP의 발현은 상피내종양의 경우 기질, 침윤성 자궁경부암의 경우 상피, 미세침윤암의 경우 기질 및 상피내에서 높은 발현정도를 보였으나, 통계학적으로 유의한 차이를 보이지는 않았다. 자궁경부암의 병기가 진행됨에 따라 맥관형성 및 TP의 발현정도가 유의하게 증가하였다. 특히, 침윤암의 경우 기질내에서 TP의 발현정도가 높았다. 결론: 이런 소견은 기질세포내에서의 TP의 발현이 암의 진행과정에 있어서 맥관형성의 성장에 중요한 역할을 하고 있을 가능성을 시사한다. TP는 자궁암에 있어서 환자의 생존율을 예측하는데 유용한 지표로 사용될 수 있을 있으리라는 가능성을 시사한다.
Abstract
Objective: The object of this study was to clarify the association of thymidine phosphorylase (TP) assessed in cancer cells and in stromal cells, with clinico-pathological factors including tumor angiogenesis and prognosis in cervical cancer. Methods: From January 1999 to December 2001, 45 cervical tissue specimens were obtained by surgical resection in the Kyung Hee University Medical Center. The study group included 25 cases in invasive squamous cell carcinomas (SCC), 9 cases in carcinoma in situ (CIS), 7 cases in microinvasive carcinoma, 4 cases in the benign uterine diseases. They were analyzed for the cellular expression of TP and the intratumoral density of microvessels by immunohistochemistry using monoclonal antibodies to TP and factor Ⅷ?related antigen, respectively. Results: Our data showed that TP expression and MVC (microvessel count) increased with histologic stage from normal, through CIS to SCC, respectively. The manifestaion of TP in the epithelium and the stroma is closely related with angiogenesis. Intraepithelial tumor revealed high expression rate of TP in the stroma, invasive cervical cancer in the epithelium, microinvasive cancer in the stroma and epithelium showing different areas of manifestation for each histologic condition, but did not show a statistically significant difference. In the case of cervical cancer, the more progressive the cancer, angiogenesis and the expression of TP increased significantly. Especially in the case of invasive cancer, stromal TP expression rate was high. Conclusion: These results suggest that thymidine phosphorylase might play an important role in angiogenesis, involving? cooperative epithelial and stromal expression of enzyme. Thymidine phosphorylase thus could be useful for a marker in assessing the survival rate in patients with cervical cancer.
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