Department of Breast Cancer Pathology and Research Laboratory, State Key Laboratory of Breast Cancer Research, Cancer Hospital of Tianjin Medical University, Tianjin, 300060, China.
Breast Cancer Res Treat. 2010 Dec;124(3):677-88. doi: 10.1007/s10549-010-0790-6. Epub 2010 Mar 9.
HAb18G is a recently identified hepatoma-associated antigen and its association with tumor growth, invasion, and angiogenesis has been studied in a variety of tumors. However, its role in the tumor progression of breast cancer has not been explored. HAb18G expression was examined by immunohistochemistry in pathological sections of 1,637 breast tissue samples and by in situ hybridization in 41 cases of invasive breast carcinomas (BC). While not detected in any cases of tumor-like conditions or benign tumors of breast, and only rarely in normal tissue (4.4%), HAb18G expression was gradually up-regulated from atypical ductal hyperplasia (27.3%), to ductal carcinoma-in situ (59.8%), and to BC (61.4%) (P < 0.01). Its expression in BC was correlated positively with C-erbB-2 expression and histologic grade (P < 0.001), and negatively with the expression of estrogen and progesterone receptors (P < 0.001). Significant differences of expression were also identified among the subgroups of BC examined: in decreasing order from invasive micropapillary carcinoma, ductal carcinoma, lobular carcinoma, papillary carcinoma, medullary carcinoma, to mucinous adenocarcinoma (P = 0.001), corresponding to their known clinical aggressiveness. In an expanded group of 186 BC patients with proper follow up, our previous findings were confirmed: HAb18G expression was significantly associated with local recurrence, distant metastasis and tumor mortality (P < 0.01). We also demonstrated that up-regulated tumor expression of HAb18G was a significant predictor of reduced disease progression-free survival rate and a shorter overall survival, independent of systemic therapies. In conclusion, this study suggests that HAb18G expression is associated with BC progression and prognosis. Further evaluation of this new marker in breast cancer is indicated.
HAb18G 是一种新鉴定的肝癌相关抗原,其与肿瘤生长、侵袭和血管生成的关系已在多种肿瘤中进行了研究。然而,其在乳腺癌肿瘤进展中的作用尚未得到探索。通过免疫组织化学方法在 1637 例乳腺组织样本的病理切片中以及在 41 例浸润性乳腺癌(BC)病例中进行了原位杂交,检查了 HAb18G 的表达。在任何肿瘤样病变或乳腺良性肿瘤中均未检测到,在正常组织中也很少检测到(4.4%),HAb18G 的表达逐渐从非典型导管增生(27.3%)、导管原位癌(59.8%)和 BC(61.4%)上调(P<0.01)。在 BC 中,其表达与 C-erbB-2 表达和组织学分级呈正相关(P<0.001),与雌激素和孕激素受体的表达呈负相关(P<0.001)。在检查的 BC 亚组中也发现了表达的显著差异:从浸润性微乳头状癌、导管癌、小叶癌、乳头状癌、髓样癌到黏液性腺癌依次降低(P=0.001),与其已知的临床侵袭性相对应。在一组 186 例有适当随访的 BC 患者中,我们的先前发现得到了证实:HAb18G 表达与局部复发、远处转移和肿瘤死亡率显著相关(P<0.01)。我们还证明,肿瘤中 HAb18G 的上调表达是疾病无进展生存率降低和总生存率缩短的显著预测因子,独立于全身治疗。总之,本研究表明 HAb18G 表达与 BC 进展和预后相关。需要进一步评估该新标志物在乳腺癌中的应用。