Androgen receptor expression is usually maintained in initial surgically resected breast cancer metastases but is often lost in end-stage metastases found at autopsy.
Androgen receptor expression is usually maintained in initial surgically resected breast cancer metastases but is often lost in end-stage metastases found at autopsy.
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DOI：
10.1016/j.humpath.2011.08.007
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发表时间：
2012-07
期刊：
影响因子：
3.3
通讯作者：
Argani P
中科院分区：
文献类型：
--
作者：
Cimino-Mathews A;Hicks JL;Illei PB;Halushka MK;Fetting JH;De Marzo AM;Park BH;Argani P
雄激素受体(AR)在约70%的原发乳腺癌中表达，是转移性乳腺癌的治疗靶点。在这里，我们检查了一组最初手术切除的转移癌和一组在尸检中获得的终末期转移癌与其匹配的原发乳腺癌的AR表达。匹配的原发和转移性乳腺癌的组织芯片用免疫组织化学标记AR、ER、PR和HER2，并将其分为以下类型：管腔(ER/PR+/HER2−)、三阴性(ER/PR/HER2−)、HER2(ER/PR−/HER2+)和管腔丢失(从原发到转移的ER/PR丢失)。在手术切除的转移癌队列中(n=16)，AR在12/16原发灶中表达，在相应的转移灶中11/12表达。其中，36%的转移灶中AR标记增强，无一例表达减弱。在尸检获得的转移癌队列中(n=16)，AR在11/16原发癌中表达，而在相应的转移癌中仅有5/11表达。其中无一例AR增加，80%的AR标记减少。AR在配对的原发癌和转移性乳腺癌中的表达在最初的表现上是压倒性的一致。这些发现验证了AR作为转移性乳腺癌的治疗靶点的有效性，并表明即使原发肿瘤为阴性，AR也可能需要在转移性乳腺癌中重新评估。然而，与ER/PR类似，AR的表达在终末期转移时往往降低并趋于完全消失，提示AR的表达在初始和终末期转移之间发生了转移。这表明在疾病进展的早期阶段进行有针对性的抗雄激素治疗是一个机会。
Androgen receptor (AR) is expressed in approximately 70% of primary breast carcinomas and is a promising therapeutic target for metastatic breast carcinoma. Here, we examine AR expression in a population of initial surgically-resected metastases and a separate cohort of end-stage metastases harvested at autopsy compared to their matched primary breast carcinomas. Tissue microarrays of matched primary and metastatic breast carcinomas were labeled by immunohistochemistry for AR, ER, PR, and Her2 and classified into the following previously-described categories: luminal (ER/PR+/Her2−), triple negative (ER/PR/Her2−), Her2 (ER/PR−/Her2+), and luminal loss (ER/PR loss from primary to metastasis). In the cohort of surgically-resected metastases (n=16), AR was expressed in 12/16 primaries and maintained in 11/12 corresponding metastases. Of these, 36% showed stronger AR labeling in the metastases and none showed a decrease. In the cohort of metastases harvested at autopsy (n=16), AR was expressed in 11/16 primary carcinomas and maintained in only 5/11 corresponding metastases. Of these, none showed increased AR and 80% showed decreased AR labeling. AR expression is overwhelmingly concordant between matched primary and metastatic breast carcinomas at initial presentation. These findings validate AR as a therapeutic target in metastatic breast carcinoma and suggest that AR may need to be reevaluated in metastases even if the primary is negative. However, similar to ER/PR, AR expression is often decreased with a trend towards complete loss in end-stage metastases, suggesting a shift of AR expression between initial and end-stage metastases. This suggests an opportunity for targeted anti-androgen therapy at an earlier stage of disease progression.