转化生长因子-α与表皮生长因子受体在乳腺癌中的相互作用。一项免疫组织学研究。

Interaction of transforming growth factor-alpha and epidermal growth factor receptor in breast carcinoma. An immunohistologic study.

作者信息

Castellani R, Visscher D W, Wykes S, Sarkar F H, Crissman J D

机构信息

Department of Pathology, Harper Hospital, Detroit, Michigan 48201.

出版信息

Cancer. 1994 Jan 15;73(2):344-9. doi: 10.1002/1097-0142(19940115)73:2<344::aid-cncr2820730218>3.0.co;2-y.

DOI:10.1002/1097-0142(19940115)73:2<344::aid-cncr2820730218>3.0.co;2-y

PMID:8293398

Abstract

BACKGROUND

Interaction of transforming growth factor-alpha (TGF-alpha) with its receptor, epidermal growth factor receptor (EGFR), has been implicated as an autoregulatory autocrine mechanism of breast epithelial proliferation.

METHODS

To examine the interrelationship and clinical relevance of TGF-alpha and EGFR in breast carcinoma, methanol-fixed cryostat sections from 73 patients were immunostained with monoclonal antibodies to epidermal growth factor (EGF), EGFR, and TGF-alpha.

RESULTS

Neither EGFR nor TGF-alpha staining was diagnostic or specific for the detection of malignant neoplastic cells. Both exhibited staining along the basal lamina of most benign ducts and lobules. TGF-alpha staining was observed in neoplastic cells in 41% and in non-neoplastic cells (peritumoral stroma and benign duct/lobular epithelium) in 36% of patients. Staining for EGF and TGF-alpha failed to correlate with node status or grade; however, TGF-alpha negative tumors were more frequently positive for estrogen receptor (ER) (70% versus 14%; P = 0.03). The presence of EGFR correlated with positive lymph node status (P = 0.004), poor differentiation (P = 0.001), and negative ER status (P = 0.0001). EGFR staining was more common in neoplasms which recurred, but this approached significance only in the group with node-negative disease (mean follow-up, 52 months; P = 0.06), and neoplastic cell TGF-alpha correlated with disease recurrence in patients with node-positive disease (no recurrence, -13% positive versus recurrence, -52% positive; P = 0.01). Concurrent TGF-alpha/EGFR staining, present in 18% of tumors, also was predictive of disease recurrence (no recurrence, 3% positive for both versus recurrence, 31% positive for both, P = 0.03).

CONCLUSIONS

TGF-alpha is heterogeneously expressed in neoplastic and host-derived components of breast tumors. Concurrent EGFR/TGF-alpha immunostaining may characterize a clinically aggressive subset of breast carcinomas, possibly reflecting autocrine interaction, and conferring growth advantage or metastatic phenotype.

摘要

背景

转化生长因子-α（TGF-α）与其受体表皮生长因子受体（EGFR）的相互作用被认为是乳腺上皮增殖的一种自调节自分泌机制。

方法

为研究TGF-α和EGFR在乳腺癌中的相互关系及临床相关性，对73例患者的甲醇固定低温恒温器切片用抗表皮生长因子（EGF）、EGFR和TGF-α的单克隆抗体进行免疫染色。

结果

EGFR和TGF-α染色均不能用于诊断或特异性检测恶性肿瘤细胞。两者在大多数良性导管和小叶的基膜处均有染色。41%的患者肿瘤细胞中有TGF-α染色，36%的患者非肿瘤细胞（肿瘤周围基质和良性导管/小叶上皮）中有TGF-α染色。EGF和TGF-α染色与淋巴结状态或分级无关；然而，TGF-α阴性肿瘤雌激素受体（ER）阳性的频率更高（70%对14%；P = 0.03）。EGFR的存在与阳性淋巴结状态（P = 0.004）、低分化（P = 0.001）和ER阴性状态（P = 0.0001）相关。EGFR染色在复发肿瘤中更常见，但仅在淋巴结阴性疾病组中接近显著水平（平均随访52个月；P = 0.06），肿瘤细胞TGF-α与淋巴结阳性疾病患者的疾病复发相关（无复发，-13%阳性对复发，-52%阳性；P = 0.01）。18%的肿瘤中同时存在TGF-α/EGFR染色，也可预测疾病复发（无复发，两者均阳性3%对复发，两者均阳性31%，P = 0.03）。