MTAP缺乏對於上尿路上皮病人癌預後之影響
李威明1, 2, 3,4、吳文正1,4,5、李經家1,4,6、柯宏龍1,2,4、韋又菁7、葉信志1,4,6、
李健逢8、黃俊農1,4、黃俊雄1,4
高雄醫學大學附設中和紀念醫院泌尿科1; 高雄醫學大學醫學研究所2; 衛生福利部屏東醫院3,; 高雄醫學大學醫學系泌尿科4; 高雄市立小港醫院泌尿科5高雄市立大同醫院泌尿科6; 高雄市立大同醫院病理科7;奇美醫學中心病理科8
The impact of Methylthioadenosine Phosphorylase (MTAP) Deficiency in Patients with Upper Tract Urothelial Carcinoma
Wei-Ming Li 1,2,3,4, Wen-Jeng Wu 1,4,5, Ching-Chia Li 1,4,6, Hung-Lung Ke 1,2,4, Yu-Ching Wei7, Hsin-Chin Yen1,4,6, Chien-Feng Li8, Chun-Nung Huang 1, 4, Chun-Hsiung Huang 1,4
1Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
2 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
3 Pingtung Hospital, Ministry of Health and Welfare, Executive Yuan, Pingtung, Taiwan
4 Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
5 Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
6 Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
7 Department of Pathology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
8Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan
Purpose: Urothelial carcinomas(UCs) involve recurrent chromosome 9p deletions. Methylthioadenosine phosphorylase (MTAP) on 9p21.3is a proposed functional tumor suppressor gene. The role of MTAP in upper tract UC (UTUC) is unknown. We aimed to investigate MTAP’s association with disease characteristics and oncologic outcomes in UTUC patients undergoing radical nephroureterectomy (RNU).
Materials and Methods: Using immunohistochemistry, we investigated MTAP expression in 340 UTUC patients treated with RNU from1996–2004, and correlated it with clinicopathologic characteristics and clinical outcomes. Univariate and multivariate Cox regression analyses evaluated the association of MTAP expression with disease-specific survival (DSS) and metastasis-free survival (MeFS).
Results: MTAP was deficient in 119 (35.0%) patients. MTAP deficiency was significantly associated with higher pathologic stage (p<0.001), lymph node metastasis (p<0.001), high grade (p=0.008), vascular invasion (p=0.001), perineural invasion(p=0.001), and higher mitotic rate (p=0.016).Sixty (17.6%) patients died of UTUC and 70 (20.6%) developed metastasis. MTAP-deficient patients demonstrated significantly worse DSS (58.1% vs.89.3%; p<0.0001) and MeFS (54.7% vs.87.9%; p<0.0001) at five years than those with intact expression. MTAP deficiency was independently associated with cancer-specific mortality (hazard ratio [HR]:2.213, p=0.019; 95% confidence interval [CI]:1.141–4.293) and metastasis development (HR:2.867, p<0.001; 95% CI:1.601–5.106).
Conclusions: MTAP deficiency is associated with aggressive cancer phenotype and unfavorable oncologic outcomes, suggesting it may be a new biomarker and provide additional prognostic information in UTUC patients undergoing RNU.