Downey S E, Hoyland J, Freemont A J, Knox F, Walls J, Bundred N J
Department of Pathological Sciences, University of Manchester, U.K.
J Pathol. 1997 Oct;183(2):212-7. doi: 10.1002/(SICI)1096-9896(199710)183:2<212::AID-PATH920>3.0.CO;2-O.
Parathyroid hormone-related protein (PTHrP) is the cause of humoral hypercalcaemia of malignancy and interacts with parathyroid hormone (PTH) receptors. Breast cancer cells produce PTHrP in vitro and in vivo. The breast cancer cell line MCF-7, which products PTHrP and expresses PTHrP receptors, proliferates in response to PTHrP. The aim of these studies was to determine the tissue location of PTHrP/PTH receptors (PTHrPR) in primary breast carcinomas and to establish whether they had the potential to respond to PTHrP. The cellular location of mRNA for the PTHrP/PTH receptor was identified using in situ hybridization in primary breast carcinomas and normal breast tissue. Immunohistochemistry for PTHrP was carried out on the same specimens. Tumours were assessed and scored by two observers using the product of intensity of signal and number of positive tumour cells (possible range 0-9). Tumours were also assessed for Ki-67 expression by counting positive nuclei. Non-malignant ductular epithelium expressed mRNA for the PTHrP receptor (mean score 2.6, range 1-4). Breast carcinomas (mean score 4.4, range 0-9) showed variable expression of PTHrP receptor mRNA: eight tumours were negative, 50 had scores similar to normal breast tissue, and 49 had higher scores for the receptor. Levels of expression of the receptor within the primary breast carcinomas were unrelated to immunohistochemical detection of PTHrP or to any standard prognostic factor. There was a significant (P = 0.05) relationship between Ki-67 and PTHrPR expression in individual tumours. The presence of PTHrP and its receptor in normal breast epithelium and breast carcinomas demonstrates that most breast tumours are able to respond to PTHrP. The Ki-67 data suggest that PTHrP is a potential autocrine growth factor in primary breast carcinoma.
甲状旁腺激素相关蛋白（PTHrP）是恶性肿瘤体液性高钙血症的病因，且可与甲状旁腺激素（PTH）受体相互作用。乳腺癌细胞在体内外均可产生PTHrP。能产生PTHrP并表达PTHrP受体的乳腺癌细胞系MCF-7可对PTHrP产生增殖反应。这些研究的目的是确定原发性乳腺癌中PTHrP/PTH受体（PTHrPR）的组织定位，并确定它们是否具有对PTHrP产生反应的潜力。采用原位杂交技术在原发性乳腺癌和正常乳腺组织中鉴定PTHrP/PTH受体mRNA的细胞定位。对相同标本进行PTHrP的免疫组织化学检测。由两名观察者根据信号强度与阳性肿瘤细胞数量的乘积对肿瘤进行评估和评分（可能范围为0 - 9）。还通过计数阳性细胞核来评估肿瘤的Ki-67表达情况。非恶性导管上皮表达PTHrP受体的mRNA（平均评分为2.6，范围为1 - 4）。乳腺癌（平均评分为4.4，范围为0 - 9）显示PTHrP受体mRNA表达存在差异：8个肿瘤为阴性，50个肿瘤的评分与正常乳腺组织相似，49个肿瘤的受体评分更高。原发性乳腺癌内受体的表达水平与PTHrP的免疫组织化学检测或任何标准预后因素均无关。在单个肿瘤中，Ki-67与PTHrPR表达之间存在显著（P = 0.05）相关性。正常乳腺上皮和乳腺癌中存在PTHrP及其受体表明大多数乳腺肿瘤能够对PTHrP产生反应。Ki-67数据提示PTHrP是原发性乳腺癌中一种潜在的自分泌生长因子。
