Department of Surgery, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan.
Anticancer Res. 2012 Aug;32(8):3069-75.
Aromatase is one of the key estrogen-producing enzymes and is regarded as one of the therapeutic targets in estrogen receptor-positive breast cancer patients. Human colon carcinoma has also been recently proposed as being an estrogen-responsive malignancy, but the detailed status of aromatase has not yet been reported. Therefore, in this study, we evaluated the aromatase expression in colon carcinoma using immunohistochemistry and real-time polymerase chain reaction. Aromatase mRNA was significantly higher (p=0.03) in colon carcinoma than in the corresponding non-neoplastic mucosa (n=31). Aromatase immunoreactivity tended to be positively associated with the intratumoral concentration of estrogens (n=53), and in particular, the concentration of estradiol was significantly higher (p=0.02) in aromatase-positive cases in men. Aromatase immunoreactivity was detected in the cytoplasm of the carcinoma cells in 217/328 (65%) examined colon carcinoma cases. Aromatase immunoreactivity was significantly positively correlated with tubular differentiation, and inversely correlated with Ki-67 labeling index, although not necessarily correlated with the clinical outcome of the patients. All these results demonstrate that colon carcinoma expresses functional aromatase, and that estrogens are locally synthesized in the tumor tissues. The findings reported here could contribute to a better understanding of the actions of estrogen in colon carcinoma.
芳香酶是一种关键的雌激素生成酶，被认为是雌激素受体阳性乳腺癌患者的治疗靶点之一。最近有人提出人类结肠癌也是一种雌激素反应性恶性肿瘤，但芳香酶的详细情况尚未报道。因此，本研究采用免疫组织化学和实时聚合酶链反应评估了结肠癌中的芳香酶表达。芳香酶 mRNA 在结肠癌中明显高于相应的非肿瘤黏膜（n=31）（p=0.03）。芳香酶免疫反应性与肿瘤内雌激素浓度呈正相关（n=53），特别是在男性芳香酶阳性病例中，雌二醇浓度明显更高（p=0.02）。在 328 例结肠癌检查病例中，有 217 例（65%）检测到癌细胞胞质中的芳香酶免疫反应性。芳香酶免疫反应性与管状分化呈显著正相关，与 Ki-67 标记指数呈负相关，但与患者的临床结果不一定相关。所有这些结果表明，结肠癌表达功能性芳香酶，雌激素在肿瘤组织中局部合成。本研究结果有助于更好地理解雌激素在结肠癌中的作用。
