UNSW Department of Surgery, Cancer Research Laboratory, St George Hospital, Kogarah, Sydney, NSW 2217, Australia.
Pathol Oncol Res. 2009 Dec;15(4):671-8. doi: 10.1007/s12253-009-9170-0. Epub 2009 Apr 29.
Gender influence on survival in mesothelioma has been observed in several large clinical series. However, this gender effect has not been investigated. Female patients often have less aggressive tumors and survive longer. However, few studies in the literature have explained the molecular basis of this finding. Understanding this difference at a molecular level may offer the hope of improving survival via hormonal manipulation.We investigate the expression of Ki-67 and sex steroid receptors; estrogen receptors (ER), progesterone receptors (PR) and androgen receptors (AR) to elucidate any pathognomonic difference that characterize this gender difference. Positive expression of markers was observed in 95% (Ki-67), 80% (ER), 100% (PR) and 65% (AR) of patients. Expression of markers between gender showed a higher Ki-67 in males (M = 1.3%, F = 0.6%), higher estrogen receptor in females (M = 0.6%, F = 1.7%) and higher progesterone receptor in females (M = 1.0%, F = 1.4%). Twenty patients were treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in our peritonectomy unit. Paraffin sections of the tumor specimens were retrieved for immunohistochemical analysis. The immunostaining was performed using monoclonal mouse anti-human antibodies on an autostainer (Autostainer Plus; Dako, Inc.). The intensity of the stains were quantified using the Image-Pro Plus (IPP) 4.5 (Media Cybernetics, Silver Spring, MD). For the first time, we demonstrate the presence of sex steroid receptors in peritoneal mesothelioma. Once the exact functional effects of these receptors are understood, the use of established therapeutic options that are clinically available to target the sex steroid pathway may become a reality.
性别对间皮瘤生存的影响在几个大型临床系列中得到了观察。然而,这种性别效应尚未得到研究。女性患者的肿瘤往往不那么具有侵袭性,生存时间更长。然而,文献中的少数研究解释了这一发现的分子基础。在分子水平上理解这种差异可能为通过激素治疗改善生存提供希望。我们研究了 Ki-67 和性激素受体的表达;雌激素受体(ER)、孕激素受体(PR)和雄激素受体(AR),以阐明任何特征性差异,这些差异可作为这种性别差异的标志。在 95%(Ki-67)、80%(ER)、100%(PR)和 65%(AR)的患者中观察到标志物的阳性表达。性别之间的标志物表达显示男性的 Ki-67 更高(M = 1.3%,F = 0.6%),女性的雌激素受体更高(M = 0.6%,F = 1.7%),女性的孕激素受体更高(M = 1.0%,F = 1.4%)。我们的腹膜切除术单位对 20 名患者进行了细胞减灭术和腹腔内热灌注化疗。从肿瘤标本中取出石蜡切片进行免疫组织化学分析。免疫染色在自动染色机(Autostainer Plus;Dako,Inc.)上使用单克隆抗人类的小鼠抗体进行。使用 Image-Pro Plus(IPP)4.5(Media Cybernetics,Silver Spring,MD)对染色强度进行量化。我们首次证明了性激素受体在腹膜间皮瘤中的存在。一旦这些受体的确切功能作用得到理解,就可以使用临床上可用于靶向性激素途径的既定治疗选择。