Allred D C, Clark G M, Molina R, Tandon A K, Schnitt S J, Gilchrist K W, Osborne C K, Tormey D C, McGuire W L
Department of Pathology, University of Texas Health Science Center, San Antonio 78284-7750.
Hum Pathol. 1992 Sep;23(9):974-9. doi: 10.1016/0046-8177(92)90257-4.
Using permanent-section immunohistochemistry, we investigated the role of HER-2/neu in the development and progression of human breast cancer by measuring its overexpression in a series of hyperplastic (n = 30), dysplastic (n = 15), and malignant neoplastic (n = 708) lesions of ductal epithelium and by evaluating the relationships between overexpression and clinicopathologic features known to have prognostic significance in these lesions. The neoplasms included pure ductal carcinoma in situ (DCIS; n = 59) and infiltrating ductal carcinoma (IDC; n = 649). The latter were all node negative and stratified into IDC combined (n = 237) or not combined (n = 412) with a "significant amount" of DCIS (defined as DCIS greater than or equal to 10% of total tumor cellularity). Overexpression of HER-2/neu was not observed in any of the hyperplastic or dysplastic lesions. In contrast, it was present in 56% of pure DCIS and in 77% of the comedo subtype of this group. Only 15% of IDC overexpressed HER-2/neu. However, the rate of overexpression was significantly higher in the subset of IDC combined with DCIS compared with the subset of IDC not combined with DCIS (22% v 11%, respectively; P less than .0001). These results are consistent with the hypothesis that HER-2/neu plays a more important role in initiation than in progression of ductal carcinomas. They also suggest that overexpression decreases within individual tumors as they evolve from in situ to increasingly invasive lesions or, alternatively, that many invasive carcinomas arise de novo (ie, without progressing through a significant in situ stage) by mechanisms not involving HER-2/neu. In addition, overexpression of HER-2/neu was associated with several poor prognostic features (younger patient age, premenopause, negative estrogen receptor status, negative progesterone receptor status, and high nuclear grade) in the subset of IDC combined with DCIS. With one exception (negative estrogen receptor status) these associations were lost in IDC not combined with DCIS, also suggesting that the role of HER-2/neu changes during the progression of human breast cancer.
我们采用永久性切片免疫组织化学方法，通过检测一系列导管上皮的增生性病变（n = 30）、发育异常性病变（n = 15）和恶性肿瘤性病变（n = 708）中HER-2/neu的过表达情况，并评估过表达与这些病变中已知具有预后意义的临床病理特征之间的关系，来研究HER-2/neu在人类乳腺癌发生发展中的作用。肿瘤包括单纯导管原位癌（DCIS；n = 59）和浸润性导管癌（IDC；n = 649）。后者均为无淋巴结转移，并分为合并（n = 237）或未合并（n = 412）“大量”DCIS（定义为DCIS占肿瘤细胞总数的10%或更多）的浸润性导管癌。在任何增生性或发育异常性病变中均未观察到HER-2/neu的过表达。相比之下，在56%的单纯DCIS以及该组粉刺样亚型的77%中存在HER-2/neu过表达。只有15%的浸润性导管癌过表达HER-2/neu。然而，与未合并DCIS的浸润性导管癌亚组相比，合并DCIS的浸润性导管癌亚组中的过表达率显著更高（分别为22%和11%；P < 0.0001）。这些结果与HER-2/neu在导管癌起始阶段比进展阶段发挥更重要作用的假设一致。它们还表明，随着肿瘤从原位癌发展为侵袭性更强的病变，单个肿瘤内的过表达会降低，或者说，许多浸润性癌是通过不涉及HER-2/neu的机制从头发生（即不经过显著的原位癌阶段）。此外，在合并DCIS的浸润性导管癌亚组中，HER-2/neu的过表达与几个不良预后特征相关（患者年龄较轻、绝经前、雌激素受体阴性、孕激素受体阴性以及核分级高）。除了一个例外（雌激素受体阴性），这些相关性在未合并DCIS的浸润性导管癌中消失，这也表明HER-2/neu在人类乳腺癌进展过程中的作用发生了变化。
