King Judy A, Ofori-Acquah Solomon F, Stevens Troy, Al-Mehdi Abu-Bakr, Fodstad Oystein, Jiang Wen G
Department of Pathology, University of South Alabama, Mobile, Alabama, USA.
Breast Cancer Res. 2004;6(5):R478-87. doi: 10.1186/bcr815. Epub 2004 Jun 28.
Activated leukocyte cell adhesion molecule (ALCAM) (CD166) is an immunoglobulin molecule that has been implicated in cell migration. The present study examined the expression of ALCAM in human breast cancer and assessed its prognostic value.
The immunohistochemical distribution and location of ALCAM was assessed in normal breast tissue and carcinoma. The levels of ALCAM transcripts in frozen tissue (normal breast, n = 32; breast cancer, n = 120) were determined using real-time quantitative PCR. The results were then analyzed in relation to clinical data including the tumor type, the grade, the nodal involvement, distant metastases, the tumor, node, metastasis (TNM) stage, the Nottingham Prognostic Index (NPI), and survival over a 6-year follow-up period.
Immunohistochemical staining on tissue sections in ducts/acini in normal breast and in breast carcinoma was ALCAM-positive. Differences in the number of ALCAM transcripts were found in different types of breast cancer. The level of ALCAM transcripts was lower (P = 0.05) in tumors from patients who had metastases to regional lymph nodes compared with those patients without, in higher grade tumors compared with Grade 1 tumors (P < 0.01), and in TNM Stage 3 tumors compared with TNM Stage 1 tumors (P < 0.01). Tumors from patients with poor prognosis (with NPI > 5.4) had significantly lower levels (P = 0.014) of ALCAM transcripts compared with patients with good prognosis (with NPI < 3.4), and tumors from patients with local recurrence had significantly lower levels than those patients without local recurrence or metastases (P = 0.04). Notably, tumors from patients who died of breast cancer had significantly lower levels of ALCAM transcripts (P = 0.0041) than those with primary tumors but no metastatic disease or local recurrence. Patients with low levels of ALCAM transcripts had significantly (P = 0.009) more incidents (metastasis, recurrence, death) compared with patients with primary breast tumors with high levels of ALCAM transcripts.
In the present panel of breast cancer specimens, decreased levels of ALCAM correlated with the nodal involvement, the grade, the TNM stage, the NPI, and the clinical outcome (local recurrence and death). The data suggest that decreased ALCAM expression is of clinical significance in breast cancer, and that reduced expression indicates a more aggressive phenotype and poor prognosis.
活化白细胞细胞黏附分子（ALCAM）（CD166）是一种免疫球蛋白分子，与细胞迁移有关。本研究检测了ALCAM在人类乳腺癌中的表达，并评估了其预后价值。
评估了正常乳腺组织和癌组织中ALCAM的免疫组化分布及定位。使用实时定量PCR测定冰冻组织（正常乳腺，n = 32；乳腺癌，n = 120）中ALCAM转录本的水平。然后将结果与包括肿瘤类型、分级、淋巴结受累情况、远处转移、肿瘤-淋巴结-转移（TNM）分期、诺丁汉预后指数（NPI）以及6年随访期内的生存率等临床数据进行分析。
正常乳腺导管/腺泡以及乳腺癌组织切片的免疫组化染色显示ALCAM呈阳性。在不同类型的乳腺癌中发现了ALCAM转录本数量的差异。与无区域淋巴结转移的患者相比，有区域淋巴结转移患者的肿瘤中ALCAM转录本水平较低（P = 0.05）；与1级肿瘤相比，高级别肿瘤中ALCAM转录本水平较低（P < 0.01）；与TNM 1期肿瘤相比，TNM 3期肿瘤中ALCAM转录本水平较低（P < 0.01）。预后较差（NPI > 5.4）患者的肿瘤中ALCAM转录本水平显著低于预后良好（NPI < 3.4）的患者（P = 0.014），局部复发患者的肿瘤中ALCAM转录本水平显著低于无局部复发或转移的患者（P = 0.04）。值得注意的是，死于乳腺癌患者的肿瘤中ALCAM转录本水平显著低于患有原发性肿瘤但无转移性疾病或局部复发的患者（P = 0.0041）。与ALCAM转录本水平高的原发性乳腺癌患者相比，ALCAM转录本水平低的患者发生（转移、复发、死亡）事件的显著更多（P = 0.009）。
在本组乳腺癌标本中，ALCAM水平降低与淋巴结受累、分级、TNM分期、NPI以及临床结局（局部复发和死亡）相关。数据表明，ALCAM表达降低在乳腺癌中具有临床意义，且表达降低表明表型更具侵袭性，预后较差。
