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一种具有高亲和力和特异性的新型芳香化酶抗血清的制备:其对乳腺癌组织的临床病理意义

Preparation of a novel antiserum to aromatase with high affinity and specificity: Its clinicopathological significance on breast cancer tissue.

作者信息

Kanomata Naoki, Matsuura Shiro, Nomura Tsunehisa, Kurebayashi Junichi, Mori Taisuke, Kitawaki Jo, Moriya Takuya

机构信息

Department of Pathology, Kawasaki Medical School, Kurashiki, Japan.

Corporate Planning Department, LSI Medience Corporation, Tokyo, Japan.

出版信息

PLoS One. 2017 May 10;12(5):e0177439. doi: 10.1371/journal.pone.0177439. eCollection 2017.

Abstract

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.

摘要

芳香化酶抑制剂已广泛用于绝经后患者雌激素依赖性乳腺癌的内分泌治疗。然而,由于抗芳香化酶抗体的特异性不理想和/或可用性有限,关于芳香化酶的临床病理研究受到限制。在此,我们利用单克隆抗体标记的免疫亲和层析,在工业生产规模上制备了对人芳香化酶具有高亲和力和特异性的多克隆抗血清。我们对221例浸润性乳腺癌病例进行的初步免疫组织化学分析表明,87.3%(193/221)至少有5%的芳香化酶阳性细胞。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,癌组织中芳香化酶的表达与雌激素受体(ER)、孕激素受体(PgR)和人表皮生长因子受体2的状态无关。这种抗血清除了可用于ER和PgR外,还将适用于芳香化酶的临床病理检查,以在乳腺癌治疗中合理使用芳香化酶抑制剂。有必要对芳香化酶表达与芳香化酶抑制剂之间的关系进行进一步研究。 芳香化酶抑制剂已广泛用于绝经后患者雌激素依赖性乳腺癌的内分泌治疗。然而,由于抗芳香化酶抗体的特异性不理想和/或可用性有限,关于芳香化酶的临床病理研究受到限制。在此,我们利用单克隆抗体标记的免疫亲和层析,在工业生产规模上制备了对人芳香化酶具有高亲和力和特异性的多克隆抗血清。我们对221例浸润性乳腺癌病例进行的初步免疫组织化学分析表明,87.3%(193/221)至少有5%的芳香化酶阳性细胞。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,癌组织中芳香化酶的表达与雌激素受体(ER)、孕激素受体(PgR)和人表皮生长因子受体2的状态无关。这种抗血清除了可用于ER和PgR外,还将适用于芳香化酶的临床病理检查,以在乳腺癌治疗中合理使用芳香化酶抑制剂。有必要对芳香化酶表达与芳香化酶抑制剂之间的关系进行进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/baac/5425223/9bf6081a17a2/pone.0177439.g001.jpg

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