Sato Naoko, Takagi Kiyoshi, Suzuki Takashi, Miki Yasuhiro, Tanaka Sota, Nagase Satoru, Warita Hitoshi, Fukudo Shin, Sato Fumiko, Sasano Hironobu, Ito Kiyoshi
Tohoku University Graduate School of Medicine, Sendai, Japan.
Int J Gynecol Cancer. 2014 Nov;24(9):1549-57. doi: 10.1097/IGC.0000000000000269.
Corticotropin-releasing hormone (CRH), a major regulator of the stress response, regulates various biological functions through its interaction with CRH receptors 1 (CRHR1) and 2 (CRHR2). CRH, CRHR1, and CRHR2 have recently been reported in several types of carcinoma, but the significance of these proteins has remained largely unknown in human endometrial carcinoma.
A total of 87 endometrial carcinoma specimens were obtained from Japanese female patients who underwent surgical treatment, fixed in 10% formalin, and embedded in paraffin wax. Immunohistochemistry for CRH, CRHR1, and CRHR2 was performed, and clinical data were obtained from the medical records.
Immunopositivity of CRH, CRHR1, and CRHR2 in the specimens was 26%, 15%, and 10%, respectively. Univariate analysis revealed that immunohistochemical CRH status was positively associated with CRHR1 and CRHR2 status and that CRHR1 status was significantly associated with the risk of recurrence and poorer clinical outcome, whereas CRHR2 status was marginally associated with better prognosis for overall survival. Multivariate analysis demonstrated CRHR1 status as an independent prognostic factor for both disease-free and overall survival.
These results suggest that intratumoral CRH-CRHR1 signaling plays an important role in the progression of endometrial carcinoma and that CRHR1 is a potent prognostic factor in patients with this disease.
促肾上腺皮质激素释放激素（CRH）是应激反应的主要调节因子，通过与促肾上腺皮质激素释放激素受体1（CRHR1）和2（CRHR2）相互作用来调节各种生物学功能。最近在几种类型的癌症中报道了CRH、CRHR1和CRHR2，但这些蛋白在人子宫内膜癌中的意义仍 largely unknown。
从接受手术治疗的日本女性患者中获取了总共87份子宫内膜癌标本，用10%福尔马林固定，石蜡包埋。进行了CRH、CRHR1和CRHR2的免疫组织化学检测，并从病历中获取临床数据。
标本中CRH、CRHR1和CRHR2的免疫阳性率分别为26%、15%和10%。单因素分析显示，免疫组织化学CRH状态与CRHR1和CRHR2状态呈正相关，CRHR1状态与复发风险和较差的临床结局显著相关，而CRHR2状态与总体生存的较好预后呈微弱相关。多因素分析表明，CRHR1状态是无病生存和总体生存的独立预后因素。
这些结果表明肿瘤内CRH-CRHR1信号通路在子宫内膜癌进展中起重要作用，且CRHR1是该疾病患者的一个有力预后因素。
