Dumoff Kimberly L, Chu Christina, Xu Xiaowei, Pasha Theresa, Zhang Paul J, Acs Geza
Department of Pathology and Laboratory Medicine, Division of Gynecologic Oncology, University of Pennsylvania Medical Center, Philadelphia, PA 19104, USA.
Mod Pathol. 2005 Jan;18(1):97-104. doi: 10.1038/modpathol.3800269.
Lymphatic invasion and nodal metastasis are predictors of shorter disease-free and overall survival in carcinoma of the uterine cervix. The monoclonal antibody D2-40, which reacts with the oncofetal membrane antigen M2A, is a new selective marker for lymphatic endothelium, and has been shown to be useful in identifying the presence of lymphatic invasion in various malignant neoplasms, including cervical carcinoma. However, the reactivity of the tumor cells with D2-40 has not yet been evaluated. In this study, we examined the pattern of D2-40 immunoreactivity in a series of 138 invasive squamous cell carcinomas of the uterine cervix. We correlated the presence and extent of D2-40 immunoreactivity in the tumor cells with various clinicopathologic features, the presence of lymphatic invasion, lymph node metastasis and outcome. Diffuse or focal D2-40 immunoreactivity was present in 17 (12%) and 81 (59%) tumors, respectively, while 40 (29%) tumors showed no immunoreactivity. Lymphatic invasion and nodal metastasis were present in 56 and 29% of tumors, respectively. Tumor emboli within lymphatic spaces and metastatic tumor foci in lymph nodes showed no immunoreactivity in 86 and 80% of the cases, respectively. Lymphatic invasion and nodal metastasis were significantly more common in tumors showing low D2-40 immunoreactivity (P<0.0001 and 0.022, respectively). D2-40 immunoreactivity showed no correlation with any other clinicopathologic features examined, including tumor size, grade and FIGO stage. In univariate analysis low D2-40 immunoreactivity was significantly associated with shorter recurrence-free, but not with overall survival. Our studies suggest that D2-40 immunostaining may serve as a marker for increased risk of lymphatic invasion and tumor recurrence in cervical biopsy material. Further study of the biological function of the M2A antigen may shed some light on the interaction of tumor cells with lymphatics.
淋巴管浸润和淋巴结转移是子宫颈癌无病生存期和总生存期较短的预测因素。单克隆抗体D2-40与癌胚膜抗原M2A发生反应，是一种新的淋巴管内皮选择性标志物，已被证明可用于识别包括宫颈癌在内的各种恶性肿瘤中淋巴管浸润的存在。然而，肿瘤细胞与D2-40的反应性尚未得到评估。在本研究中，我们检测了138例子宫颈浸润性鳞状细胞癌中D2-40免疫反应性的模式。我们将肿瘤细胞中D2-40免疫反应性的存在和程度与各种临床病理特征、淋巴管浸润、淋巴结转移及预后相关联。弥漫性或局灶性D2-40免疫反应性分别存在于17例（12%）和81例（59%）肿瘤中，而40例（29%）肿瘤无免疫反应性。淋巴管浸润和淋巴结转移分别存在于56%和29%的肿瘤中。淋巴管内的肿瘤栓子和淋巴结中的转移瘤灶分别在86%和80%的病例中无免疫反应性。在D2-40免疫反应性低的肿瘤中，淋巴管浸润和淋巴结转移明显更常见（分别为P<0.0001和0.022）。D2-40免疫反应性与所检测的任何其他临床病理特征均无相关性，包括肿瘤大小、分级和国际妇产科联盟（FIGO）分期。在单因素分析中，D2-40免疫反应性低与无复发生存期显著相关，但与总生存期无关。我们的研究表明，D2-40免疫染色可作为宫颈活检材料中淋巴管浸润和肿瘤复发风险增加的标志物。对M2A抗原生物学功能的进一步研究可能有助于阐明肿瘤细胞与淋巴管的相互作用。
