Brooks S A, Leathem A J, Camplejohn R S, Gregory W
Department of Surgery, University College and London Medical School, UK.
Breast Cancer Res Treat. 1993;25(3):247-56. doi: 10.1007/BF00689839.
Abnormal cellular glycosylation as demonstrated by the binding of a lectin from Helix pomatia (HPA) to paraffin-embedded sections has been shown in several studies to be associated with aggressive biological behaviour and poor long-term patient prognosis in breast cancer. This study aims to address the possibility that expression of the HPA binding ligand may be of prognostic significance through an association with increased cellular proliferation (as measured by S-phase fraction and histological grade), anaplasia (reflected in histological grade), or ploidy (DNA index). In a 24 year retrospective study, paraffin-embedded sections of 366 primary breast cancers were stained for binding of HPA. All tumours were assessed for histological grade. Flow cytometry was performed on all cases for which sufficient tumour tissue was available (358/366 cases) and S-phase fraction (SPF) and ploidy calculated. Data regarding patient age at diagnosis, nodal status, and tumour size were also recorded. Life table analyses revealed survival advantage for HPA 'non stainers' in comparison to 'stainers' (p < 0.001); for patients with tumours of low grade vs. high grade (p < 0.001); and for those with tumours of low SPF vs. high SPF (p < 0.001). No survival advantage was shown for those with diploid vs. aneuploid tumours (p = 0.17). No association was apparent between HPA binding and grade, SPF, or ploidy (Chi squared values not significant). This was confirmed by multivariate analysis in which nodal status, tumour size, and SPF were independently predictive of survival. There was no confounding effect of grade, SPF, or ploidy upon the correlation between survival and HPA binding. HPA was, however, not independently predictive owing to its strong association with nodal status. The results of this study suggest that the prognostic significance of altered glycosylation, as detected by HPA binding, is unlikely to be through an association with proliferative rate, degree of anaplasia, or cellular ploidy, but may rather be through a direct association with the presence of nodal metastases.
几项研究表明，来自苹果螺（HPA）的凝集素与石蜡包埋切片的结合所显示的异常细胞糖基化与乳腺癌侵袭性生物学行为及患者长期预后不良相关。本研究旨在探讨HPA结合配体的表达通过与细胞增殖增加（通过S期分数和组织学分级测量）、间变（反映在组织学分级中）或倍性（DNA指数）相关联而具有预后意义的可能性。在一项为期24年的回顾性研究中，对366例原发性乳腺癌的石蜡包埋切片进行HPA结合染色。对所有肿瘤进行组织学分级评估。对所有有足够肿瘤组织的病例（358/366例）进行流式细胞术检测，并计算S期分数（SPF）和倍性。还记录了患者诊断时的年龄、淋巴结状态和肿瘤大小数据。生命表分析显示，与“染色者”相比，HPA“非染色者”具有生存优势（p < 0.001）；低级别肿瘤患者与高级别肿瘤患者相比（p < 0.001）；低SPF肿瘤患者与高SPF肿瘤患者相比（p < 0.001）。二倍体肿瘤与非整倍体肿瘤患者之间未显示出生存优势（p = 0.17）。HPA结合与分级、SPF或倍性之间无明显关联（卡方值无统计学意义）。多因素分析证实了这一点，其中淋巴结状态、肿瘤大小和SPF可独立预测生存。分级、SPF或倍性对生存与HPA结合之间的相关性无混杂影响。然而，由于HPA与淋巴结状态密切相关，它不能独立预测。本研究结果表明，通过HPA结合检测到的糖基化改变的预后意义不太可能通过与增殖率、间变程度或细胞倍性相关联，而可能是通过与淋巴结转移的存在直接相关。
