Preparation of a novel antiserum to aromatase with high affinity and specificity: Its clinicopathological significance on breast cancer tissue.
Preparation of a novel antiserum to aromatase with high affinity and specificity: Its clinicopathological significance on breast cancer tissue.
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DOI：
10.1371/journal.pone.0177439
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Moriya T
中科院分区：
文献类型：
--
作者：
Kanomata N;Matsuura S;Nomura T;Kurebayashi J;Mori T;Kitawaki J;Moriya T
芳香化酶抑制剂已广泛用于绝经后雌激素依赖性乳腺癌患者的内分泌治疗。然而，芳香化酶的临床病理学研究由于不令人满意的特异性和/或抗芳香化酶抗体的有限可用性而受到限制。在这里，我们已经产生了一个多克隆抗血清与高亲和力和特异性的人芳香化酶使用单克隆抗体标记的免疫亲和层析在工业生产规模。我们对221例浸润性乳腺癌进行了初步的免疫组化分析，结果显示87.3%（193/221）的乳腺癌中芳香化酶阳性细胞至少占5%。芳香化酶的组织学评分与pT（p = 0.019）、pN（p = 0.001）、分期（p < 0.001）、组织学分级（p = 0.003）、淋巴浸润（p <0.001）、静脉浸润（p < 0.001）和Ki-67指数（p < 0.001）呈负相关。然而，癌症芳香化酶的表达是独立的雌激素受体（ER），孕激素受体（PgR），和人表皮生长因子受体2的状态。该抗血清可用于芳香化酶及ER、PgR的临床病理学检测，为芳香化酶抑制剂在乳腺癌治疗中的合理应用提供依据。芳香化酶抑制剂之间关系的进一步研究已被广泛用于绝经后雌激素依赖性乳腺癌患者的内分泌治疗。然而，芳香化酶的临床病理学研究由于不令人满意的特异性和/或抗芳香化酶抗体的有限可用性而受到限制。在这里，我们已经产生了一个多克隆抗血清与高亲和力和特异性的人芳香化酶使用单克隆抗体标记的免疫亲和层析在工业生产规模。我们对221例浸润性乳腺癌进行了初步的免疫组化分析，结果显示87.3%（193/221）的乳腺癌中芳香化酶阳性细胞至少占5%。芳香化酶的组织学评分与pT（p = 0.019）、pN（p = 0.001）、分期（p < 0.001）、组织学分级（p = 0.003）、淋巴浸润（p <0.001）、静脉浸润（p < 0.001）和Ki-67指数（p < 0.001）呈负相关。然而，癌症芳香化酶的表达是独立的雌激素受体（ER），孕激素受体（PgR），和人表皮生长因子受体2的状态。该抗血清可用于芳香化酶及ER、PgR的临床病理学检测，为芳香化酶抑制剂在乳腺癌治疗中的合理应用提供依据。芳香化酶表达与芳香化酶抑制剂之间的关系有待进一步研究。
Aromatase inhibitors have been widely used for the endocrine treatment of estrogen-dependent breast cancer in postmenopausal patients. However, clinicopathological studies of aromatase have been limited due to unsatisfactory specificity and/or restricted availability of anti-aromatase antibodies. Here, we have generated a polyclonal antiserum with high affinity and specificity for human aromatase using a monoclonal antibody tagged immunoaffinity chromatography on an industrial production scale. Our preliminary immunohistochemical analysis of 221 invasive breast cancer cases indicated that 87.3% (193/221) had at least 5% aromatase positive cells. The histoscore for aromatase was inversely correlated with pT (p = 0.019), pN (p = 0.001), stage (p < 0.001), histologic grade (p = 0.003), lymphatic infiltration (p < 0.001), venous infiltration (p < 0.001), and Ki-67 index (p < 0.001). However, cancer aromatase expression was independent of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 statuses. This antiserum will be applicable to clinicopathological examination of aromatase in addition to ER and PgR for an appropriate use of aromatase inhibitor on the treatment of breast cancer. Further studies on the relationship between Aromatase inhibitors have been widely used for the endocrine treatment of estrogen-dependent breast cancer in postmenopausal patients. However, clinicopathological studies of aromatase have been limited due to unsatisfactory specificity and/or restricted availability of anti-aromatase antibodies. Here, we have generated a polyclonal antiserum with high affinity and specificity for human aromatase using a monoclonal antibody tagged immunoaffinity chromatography on an industrial production scale. Our preliminary immunohistochemical analysis of 221 invasive breast cancer cases indicated that 87.3% (193/221) had at least 5% aromatase positive cells. The histoscore for aromatase was inversely correlated with pT (p = 0.019), pN (p = 0.001), stage (p < 0.001), histologic grade (p = 0.003), lymphatic infiltration (p < 0.001), venous infiltration (p < 0.001), and Ki-67 index (p < 0.001). However, cancer aromatase expression was independent of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 statuses. This antiserum will be applicable to clinicopathological examination of aromatase in addition to ER and PgR for an appropriate use of aromatase inhibitor on the treatment of breast cancer. Further studies on the relationship between aromatase expression and aromatase inhibitors are warranted.