Tumor signatures of PTHLH overexpression, high serum calcium, and poor prognosis were observed exclusively in clear cell but not non clear cell renal carcinomas.
Tumor signatures of PTHLH overexpression, high serum calcium, and poor prognosis were observed exclusively in clear cell but not non clear cell renal carcinomas.
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DOI：
10.1002/cam4.270
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发表时间：
2014-08
期刊：
影响因子：
4
通讯作者：
Kubota, Yoshinobu
中科院分区：
文献类型：
--
作者：
Yao, Masahiro;Murakami, Takayuki;Shioi, Koichi;Mizuno, Nobuhiko;Ito, Hiroki;Kondo, Keiichi;Hasumi, Hisashi;Sano, Futoshi;Makiyama, Kazuhide;Nakaigawa, Noboru;Kishida, Takeshi;Nagashima, Yoji;Yamanaka, Shoji;Kubota, Yoshinobu
由于肿瘤甲状旁腺激素样激素（PTHLH）的异常分泌而导致的高血钙（Ca）是一种众所周知的副肿瘤体征，与肾细胞癌（RCC）患者的不良预后相关。然而，血清Ca和肿瘤PTHLH表达的状态尚未使用2004年世界卫生组织（WHO）肾肿瘤分类进行验证。我们回顾性分析了RCC患者初发（n = 683）和/或复发（n = 71）时的校正血清钙水平。我们还通过实时定量PCR检测了623例肾实质肿瘤标本PTHLH mRNA的表达。高血清钙伴随PTHLH过度表达仅见于透明细胞肾细胞癌，而不见于其他非透明细胞亚型肿瘤，包括乳头状、嫌色细胞、集合管、未分类和其他罕见亚型肾细胞癌或良性嗜酸细胞瘤和血管平滑肌脂肪瘤。在透明细胞肾细胞癌中，PTHLH表达在男性患者中显著增高，并且与症状表现、较高级别和较高分期病例相关，而与VHL基因状态无关。单因素分析表明，PTHLH高表达与接受标准肾切除术的患者的总生存期（OS）和无病生存期（DFS）的不良结局密切相关。进一步的多变量考克斯分析显示PTHLH表达仍然是OS的独立预后参数，但不是DFS的独立预后参数。这些数据表明，先前表征的由于PTHLH高表达和预后不良而导致的高血清Ca的肿瘤特征是透明细胞RCC特异性特征，而这些特征在非透明细胞RCC中很少见。
High serum calcium (Ca) due to aberrant secretion of tumor parathyroid hormone-like hormone (PTHLH) is a well-known paraneoplastic sign and is associated with poor prognosis in patients with renal cell carcinoma (RCC). However, the status of serum Ca and tumor PTHLH expression have not been verified using the 2004 World Health Organization (WHO) renal tumor classification. We retrospectively reviewed corrected serum Ca levels at initial onset (n = 683) and/or as of recurrence (n = 71) in patients with RCC. We also examined a total of 623 renal parenchymal tumor samples for PTHLH mRNA expressions by quantitative real-time PCR. High serum Ca concomitant with PTHLH overexpression in tumors was observed exclusively in clear cell RCC but not in other non clear cell subtype tumors, including papillary, chromophobe, collecting-duct, unclassified, and other rare subtype RCCs or in benign oncocytomas and angiomyolipomas. In clear cell RCC, PTHLH expression was significantly high in male patients, and was associated with a symptomatic presentation, higher grade, and higher stage cases, whereas it was not associated with VHL gene status. Univariate analyses demonstrated that high PTHLH expression was strongly associated with poor outcome both in overall survival (OS) and disease-free survival (DFS) for patients who underwent standard nephrectomy. Further multivariate Cox analyses revealed that the PTHLH expressions remained as independent prognostic parameters for OS but not for DFS. These data suggest that the previously characterized tumor signatures of high serum Ca due to high PTHLH expression and poor prognosis are clear cell RCC-specific features, whereas these characteristics are rare in non clear cell RCCs.
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影响因子：
2.4
作者：
Hu, Brian;Lara, Primo N., Jr.;Evans, Christopher P.
通讯作者：
Evans, Christopher P.
DOI：
10.1038/nrurol.2010.47
发表时间：
2010-05
期刊：
Nature reviews. Urology
影响因子：
--
作者：
通讯作者：
--
影响因子：
10.5
作者：
Linehan WM;Bratslavsky G;Pinto PA;Schmidt LS;Neckers L;Bottaro DP;Srinivasan R
通讯作者：
Srinivasan R
影响因子：
45.3
作者：
Motzer, RJ;Mazumdar, M;Ferrara, J
通讯作者：
Ferrara, J
影响因子：
4.7
作者：
Danilin, Sabrina;Sourbier, Carole;Massfelder, Thierry
通讯作者：
Massfelder, Thierry