Scher H I, Sarkis A, Reuter V, Cohen D, Netto G, Petrylak D, Lianes P, Fuks Z, Mendelsohn J, Cordon-Cardo C
Genitourinary Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Cornell University Medical College, New York, NY 10021, USA.
Clin Cancer Res. 1995 May;1(5):545-50.
The autocrine/paracrine interaction of the epidermal growth factor receptor (EGFr) and transforming growth factor alpha (TGF-alpha) has been implicated in prostate cancer cell growth and proliferation. To evaluate the role of EGFr and TGF-alpha in prostate cancer progression, we studied the immunohistochemical staining pattern of EGFr and TGF-alpha in malignant primary and hormone-independent metastatic prostate lesions. The specimens evaluated included 37 primary carcinomas (34 hormone-naive and 3 hormone-refractory tumors) and 22 metastases. For each specimen, the pattern of expression was evaluated and staining reactivities graded from 0-3, with 0 representing no staining and 3 representing homogeneous and intense staining. Primary malignant prostate epithelial cells in areas with discrete gland formation showed strong EGFr immunostaining, while stromal cells were generally nonreactive. In untreated primary tumors, TGF-alpha expression was primarily in the stroma, while epithelial cells were weakly positive in several cases. Malignant epithelial cells adjacent to neural elements that stained positive for TGF-alpha was frequently observed. A homogeneous staining pattern for EGFr was noted in 17 (89%) of 19 evaluable androgen-independent-refractory metastases, while TGF-alpha expression was found in 14 (78%) of 18 evaluable cases. Overall, 14 of 18 androgen-independent metastases coexpressed the receptor and the ligand. These results suggest that, unlike primary prostate tumors where a paracrine relationship between EGFr and TGF-alpha appears to predominate, the potential for autocrine stimulation may exist in the majority of metastatic androgen-independent tumors. Furthermore, the changing pattern of expression as the disease evolves from the localized hormone-naive to metastatic androgen-independent condition suggests that strategies aimed at blocking this growth factor pathway may be of therapeutic importance for androgen-independent disease.
表皮生长因子受体（EGFr）与转化生长因子α（TGF-α）的自分泌/旁分泌相互作用与前列腺癌细胞的生长和增殖有关。为了评估EGFr和TGF-α在前列腺癌进展中的作用，我们研究了EGFr和TGF-α在原发性恶性和激素非依赖性转移性前列腺病变中的免疫组织化学染色模式。评估的标本包括37例原发性癌（34例激素初治肿瘤和3例激素难治性肿瘤）和22例转移灶。对于每个标本，评估表达模式并将染色反应性从0到3分级，0表示无染色，3表示均匀且强烈染色。在有离散腺泡形成区域的原发性恶性前列腺上皮细胞显示出强烈的EGFr免疫染色，而基质细胞通常无反应。在未经治疗的原发性肿瘤中，TGF-α表达主要在基质中，而上皮细胞在少数情况下呈弱阳性。经常观察到与TGF-α染色阳性的神经成分相邻的恶性上皮细胞。在19例可评估的雄激素非依赖性难治性转移灶中，17例（89%）观察到EGFr呈均匀染色模式，而在18例可评估病例中的14例（78%）发现有TGF-α表达。总体而言，18例雄激素非依赖性转移灶中有14例同时表达受体和配体。这些结果表明，与原发性前列腺肿瘤中EGFr和TGF-α之间似乎以旁分泌关系为主不同，大多数转移性雄激素非依赖性肿瘤可能存在自分泌刺激的可能性。此外，随着疾病从局限性激素初治状态发展到转移性雄激素非依赖性状态，表达模式的变化表明，针对阻断这种生长因子途径的策略可能对雄激素非依赖性疾病具有治疗重要性。
