Mansour O A, Zekri A R, Harvey J, Teramoto Y, el-Ahmady O
Tumor Marker Oncology Research Center Al-Azhar University, Egypt.
Anticancer Res. 1997 Jul-Aug;17(4B):3101-6.
Amplification of erbB-1 and c-erbB-2 genes has been shown in human breast cancer. Expression of these protooncogenes results in production of epidermal growth factor receptor (EGFR) and c-erbB-2. Both are transmembrane receptors with tyrosine kinase activity. Recent data have indicated that the external domain of c-erbB-2 is shed into the culture supernatant of certain breast cancer cell lines and sera of breast cancer patients. A body of literature has shown that the overexpression of these receptors in malignant tissue and c-erbB-2 when shed into serum is associated with bad prognosis. In the present work, tissue EGFR and c-erbB-2 were determined in the membrane fractions of histopathologically verified malignant and normal tissues from the same breast of 94 patients. These values were also determined in 48 tissue specimens of benign mastopathies. Serum c-erbB-2 was quantified in breast cancer patients (n = 105), patients with benign breast disease (n = 48) and 30 apparently healthy women as controls. Patients were followed up by determination of serum c-erbB-2 for one year and clinically for three years to detect any distant metastasis or recurrence. The levels of tissue and serum c-erbB-2 and Estrogen receptors were significantly higher in the carcinomas and sera of breast cancer patients than benign breast diseases or normal controls. Follow-up, although short, of pre-operative serum c-erbB-2 showed a prognostic value (P = 0.007) better than that of tumor size (P = 0.04), EGFR (P = 0.18), nodal involvement (P = 0.25) and tissue c-erbB-2 (P = 0.85). The shedding of soluble fragments of c-erbB-2 into the serum seems to be a characteristic of the potentially malignant cell. The EGFR mean level, however, was significantly lower in malignant tissues than benign and normal ones. A new definition of EGFR status was developed. Accordingly, the recurrence of the disease was more frequent among patients with negative EGFR. The present work did not reveal any correlation between tissue, serum c-erbB-2 or EGFR on one hand and age, menopausal status, stage, histological type and grade of carcinomas and nodal involvement on the other hand. The present work showed an inverse correlation between estrogen receptor level and level of EGFR in malignant tissues.
erbB-1和c-erbB-2基因的扩增已在人类乳腺癌中得到证实。这些原癌基因的表达导致表皮生长因子受体（EGFR）和c-erbB-2的产生。二者均为具有酪氨酸激酶活性的跨膜受体。最近的数据表明，c-erbB-2的胞外结构域可脱落至某些乳腺癌细胞系的培养上清液及乳腺癌患者的血清中。大量文献表明，这些受体在恶性组织中的过表达以及c-erbB-2脱落后进入血清与预后不良相关。在本研究中，对94例患者同一乳房经组织病理学证实的恶性和正常组织的膜组分中的组织EGFR和c-erbB-2进行了检测。在48例乳腺良性病变的组织标本中也测定了这些值。对乳腺癌患者（n = 105）、乳腺良性疾病患者（n = 48）和30名明显健康的女性作为对照进行血清c-erbB-2定量检测。通过测定血清c-erbB-2对患者进行为期一年的随访，并进行为期三年的临床随访，以检测是否有远处转移或复发。乳腺癌患者的癌组织和血清中组织和血清c-erbB-2以及雌激素受体水平显著高于乳腺良性疾病或正常对照。术前血清c-erbB-2的随访时间虽短，但显示出比肿瘤大小（P = 0.04）、EGFR（P = 0.18）、淋巴结受累情况（P = 0.25）和组织c-erbB-2（P = 0.85）更好的预后价值（P = 0.007）。c-erbB-2可溶性片段脱落至血清中似乎是潜在恶性细胞的一个特征。然而，恶性组织中的EGFR平均水平显著低于良性和正常组织。提出了EGFR状态的新定义。据此，EGFR阴性的患者疾病复发更为频繁。本研究未发现组织、血清c-erbB-2或EGFR与年龄、绝经状态、分期、癌组织学类型和分级以及淋巴结受累情况之间存在任何相关性。本研究显示恶性组织中雌激素受体水平与EGFR水平呈负相关。
