肾细胞癌骨转移病理特点分析与配对研究
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摘要
目的分析肾细胞癌骨转移组织病理及免疫组织化学特点,探讨肾细胞癌骨转移的病理学相关特点与转移高危因素。方法回顾性分析海军军医大学(第二军医大学)长征医院2012年1月至2017年12月收治的经病理确诊的1 694例肾细胞癌患者(未发生骨转移)与133例肾细胞癌骨转移患者的病理学特征与免疫组织化学特点,并对25例先后或同时于长征医院切除肾癌原发灶和骨转移灶的肾细胞癌患者的病理资料进行配对分析。结果未发生骨转移肾细胞癌患者中男性所占比例(70.1%,1 188/1 694)低于骨转移肾细胞癌患者(84.2%,112/133),肾透明细胞癌所占比例(83.4%,1 412/1 694)低于骨转移肾细胞癌患者(93.6%,103/110),差异均有统计学意义(P均<0.01)。在未发生骨转移肾透明细胞癌患者和骨转移肾透明细胞癌患者中,Fuhrman核分级Ⅲ/Ⅳ级者分别占17.7%(247/1 398)和51.6%(32/62),差异有统计学意义(P<0.001)。在配对分析的25例骨转移肾细胞癌患者中,11例(44.0%)组织病理学提示肿瘤侵犯或突破肾包膜,同期未发生骨转移肾细胞癌患者中18.9%(320/1 694)病理检查提示侵犯或突破肾包膜,发生骨转移的肾细胞癌患者侵犯或突破肾包膜的比例高于同期未发生骨转移的肾细胞癌患者(P=0.002)。配对分析显示肾脏原发灶中Ki-67标记指数低于骨转移灶[中位数(下四分位数,上四分位数):5.0%(2.0%,6.0%) vs 6.0%(3.0%,15.0%),P<0.001]。结论肾透明细胞癌较肾非透明细胞癌更容易发生骨转移,男性、Fuhrman核分级Ⅲ/Ⅳ级和侵犯肾被膜是发生骨转移的高危因素。骨转移灶Ki-67标记指数较原发灶高,提示原发灶与转移灶的病理特点并不完全相同,获取骨转移组织进行病理分析或可指导治疗。
Objective To analyze the clinicopathological and immunohistochemical characteristics of renal cell carcinoma(RCC) bone metastasis, and to explore the pathological characteristics and high-risk factors of bone metastasis in RCC patients. Methods A retrospective study was conducted on the clinicopathological and immunohistochemical characteristics of 1 694 RCC patients without bone metastasis and 133 RCC patients with bone metastasis, who were admitted to Changzheng Hospital of Naval Medical University(Second Military Medical University) from Jan. 2012 to Dec. 2017.The paired pathological data of primary and bone metastatic lesions were analyzed in 25 RCC patients whose primary and bone metastatic lesions were removed successively or simultaneously in Changzheng Hospital. Results Compared with the RCC patients with bone metastasis, the proportion of males was significantly lower in the RCC patients without bone metastasis(70.1% [1 188/1 694] vs 84.2% [112/133], P<0.01), and the proportion of clear cell RCC(CCRCC) patients was also significantly lower(83.4% [1 412/1 694] vs 93.6% [103/110], P=0.004). Fuhrman nuclear grade Ⅲ/Ⅳ accounted for 17.7%(247/1 398) and 51.6%(32/62) in the CCRCC patients without bone metastasis and with bone metastasis, respectively, and the difference was significant(P<0.001). The proportion of the patients having tumor invasion or breakthrough of the renal capsule was44.0%(11/25) in the 25 patients with bone metastasis having matched data and 18.9%(320/1 694) in the RCC patients without bone metastasis, and the difference was significant(P=0.002). Matching analysis showed that the Ki-67 marker index was significantly lower in the primary lesions than that in the bone metastatic lesions(median [lower quartile, upper quartile]: 5.0% [2.0%, 6.0%] vs6.0% [3.0%, 15.0%], P<0.001). Conclusion CCRCC is more prone to bone metastasis than non-CCRCC. Male, Fuhrman gradeⅢ/Ⅳ and invasion of renal capsule are high risk factors of bone metastasis. The Ki-67 marker index is higher in bone metastatic lesions than that in primary tumor, suggesting that the pathological characteristics of primary and bone metastatic lesions are not identical and the pathological analysis may guide treatment.
Objective To analyze the clinicopathological and immunohistochemical characteristics of renal cell carcinoma(RCC) bone metastasis, and to explore the pathological characteristics and high-risk factors of bone metastasis in RCC patients. Methods A retrospective study was conducted on the clinicopathological and immunohistochemical characteristics of 1 694 RCC patients without bone metastasis and 133 RCC patients with bone metastasis, who were admitted to Changzheng Hospital of Naval Medical University(Second Military Medical University) from Jan. 2012 to Dec. 2017.The paired pathological data of primary and bone metastatic lesions were analyzed in 25 RCC patients whose primary and bone metastatic lesions were removed successively or simultaneously in Changzheng Hospital. Results Compared with the RCC patients with bone metastasis, the proportion of males was significantly lower in the RCC patients without bone metastasis(70.1% [1 188/1 694] vs 84.2% [112/133], P<0.01), and the proportion of clear cell RCC(CCRCC) patients was also significantly lower(83.4% [1 412/1 694] vs 93.6% [103/110], P=0.004). Fuhrman nuclear grade Ⅲ/Ⅳ accounted for 17.7%(247/1 398) and 51.6%(32/62) in the CCRCC patients without bone metastasis and with bone metastasis, respectively, and the difference was significant(P<0.001). The proportion of the patients having tumor invasion or breakthrough of the renal capsule was44.0%(11/25) in the 25 patients with bone metastasis having matched data and 18.9%(320/1 694) in the RCC patients without bone metastasis, and the difference was significant(P=0.002). Matching analysis showed that the Ki-67 marker index was significantly lower in the primary lesions than that in the bone metastatic lesions(median [lower quartile, upper quartile]: 5.0% [2.0%, 6.0%] vs6.0% [3.0%, 15.0%], P<0.001). Conclusion CCRCC is more prone to bone metastasis than non-CCRCC. Male, Fuhrman gradeⅢ/Ⅳ and invasion of renal capsule are high risk factors of bone metastasis. The Ki-67 marker index is higher in bone metastatic lesions than that in primary tumor, suggesting that the pathological characteristics of primary and bone metastatic lesions are not identical and the pathological analysis may guide treatment.
引文
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[14]DU Y,PAHERNIK S,HADASCHIK B,TEBER D,DUENSING S,J腉ER D,et al.Survival and prognostic factors of patients with renal cell cancer with bone metastasis in the era of targeted therapy:a singleinstitution analysis[J/OL].Urol Oncol,2016,34:433.e1-8.doi:10.1016/j.urolonc.2016.05.017.
[15]张力杰,黄晓波,徐涛,许清泉,王晓峰.肾癌原发灶与骨转移灶配对组织的免疫组化分析[J].中华泌尿外科杂志,2014,35:561-564.
[16]董毅,王德胜,吴震杰,刘冰,鲍一,王坚超,等.肾细胞癌骨转移114例临床特点分析[J].临床泌尿外科杂志,2018,33:342-345.
[17]王达,胡劲博,刘玉杰,何韶辉,龚海熠,张浩,等.不明原发灶骨转移癌的诊疗进展[J].中国骨与关节杂志,2017,6:716-720.
[18]ESCUDIER B,POWLES T,MOTZER R J,OLENCKI T,ARéN FRONTERA O,OUDARD S,et al.Cabozantinib,a new standard of care for patients with advanced renal cell carcinoma and bone metastases?Subgroup analysis of the METEOR trial[J].J Clin Oncol,2018,36:765-772.
[19]LUKASZEWSKI B,NAZAR J,GOCH M,LUKASZEWSKA M,STEPINSKI A,JURCZYK M U.Diagnostic methods for detection of bone metastases[J].Contemp Oncol(Pozn),2017,21:98-103.
[20]RUATTA F,DEROSA L,ESCUDIER B,COLOMBA E,GUIDA A,BACIARELLO G,et al.Prognosis of renal cell carcinoma with bone metastases:experience from a large cancer centre[J].Eur J Cancer,2019,107:79-85.
[2]SHINDER B M,RHEE K,FARRELL D,FARBER NJ,STEIN M N,JANG T L,et al.Surgical management of advanced and metastatic renal cell carcinoma:a multidisciplinary approach[J/OL].Front Oncol,2017,7:107.doi:10.3389/fonc.2017.00107.
[3]PRASAD S R,HUMPHREY P A,CATENA J R,NARRAV R,SRIGLEY J R,CORTEZ A D,et al.Common and uncommon histologic subtypes of renal cell carcinoma:imaging spectrum with pathologic correlation[J].Radiographics,2006,26:1795-1810.
[4]WOODWARD E,JAGDEV S,MCPARLAND L,CLARK K,GREGORY W,NEWSHAM A,et al.Skeletal complications and survival in renal cancer patients with bone metastases[J].Bone,2011,48:160-166.
[5]UMER M,MOHIB Y,ATIF M,NAZIM M.Skeletal metastasis in renal cell carcinoma:a review[J].Ann Med Surg(Lond),2018,27:9-16.
[6]王林辉,董毅.重视肾癌骨转移的个体化治疗[J].临床泌尿外科杂志,2018,33:337-341.
[7]CHEN S C,KUO P L.Bone metastasis from renal cell carcinoma[J/OL].Int J Mol Sci,2016,17.pii:E987.doi:10.3390/ijms17060987.
[8]BARATA P C,RINI B I.Treatment of renal cell carcinoma:current status and future directions[J].CACancer J Clin,2017,67:507-524.
[9]DELAHUNT B,EBLE J N,EGEVA D L,SAMARATUNGA H.Grading of renal cell carcinoma[J].Histopathology,2019,74:4-17.
[10]SIEGEL R L,MILLER K D,JEMAL A.Cancer statistics,2018[J].CA Cancer J Clin,2018,68:7-30.
[11]DENG F M,MELAMED J.Histologic variants of renal cell carcinoma:does tumor type influence outcome?[J].Urol Clin North Am,2012,39:119-132,v.
[12]MOCH H,CUBILLA A L,HUMPHREY P A,REUTERV E,ULBRIGHT T M.The 2016 WHO classification of tumours of the urinary system and male genital organs-part a:renal,penile,and testicular tumours[J].Eur Urol,2016,70:93-105.
[13]CAIRNS P.Renal cell carcinoma[J].Cancer Biomark,2010,9(1/2/3/4/5/6):461-473.
[14]DU Y,PAHERNIK S,HADASCHIK B,TEBER D,DUENSING S,J腉ER D,et al.Survival and prognostic factors of patients with renal cell cancer with bone metastasis in the era of targeted therapy:a singleinstitution analysis[J/OL].Urol Oncol,2016,34:433.e1-8.doi:10.1016/j.urolonc.2016.05.017.
[15]张力杰,黄晓波,徐涛,许清泉,王晓峰.肾癌原发灶与骨转移灶配对组织的免疫组化分析[J].中华泌尿外科杂志,2014,35:561-564.
[16]董毅,王德胜,吴震杰,刘冰,鲍一,王坚超,等.肾细胞癌骨转移114例临床特点分析[J].临床泌尿外科杂志,2018,33:342-345.
[17]王达,胡劲博,刘玉杰,何韶辉,龚海熠,张浩,等.不明原发灶骨转移癌的诊疗进展[J].中国骨与关节杂志,2017,6:716-720.
[18]ESCUDIER B,POWLES T,MOTZER R J,OLENCKI T,ARéN FRONTERA O,OUDARD S,et al.Cabozantinib,a new standard of care for patients with advanced renal cell carcinoma and bone metastases?Subgroup analysis of the METEOR trial[J].J Clin Oncol,2018,36:765-772.
[19]LUKASZEWSKI B,NAZAR J,GOCH M,LUKASZEWSKA M,STEPINSKI A,JURCZYK M U.Diagnostic methods for detection of bone metastases[J].Contemp Oncol(Pozn),2017,21:98-103.
[20]RUATTA F,DEROSA L,ESCUDIER B,COLOMBA E,GUIDA A,BACIARELLO G,et al.Prognosis of renal cell carcinoma with bone metastases:experience from a large cancer centre[J].Eur J Cancer,2019,107:79-85.