Gazic B, Pizem J, Bracko M, Cufer T, Borstnar S, Pohar-Marinsek Z, Us-Krasovec M
Department of Pathology, Institute of Oncology, Ljubljana, Slovenia.
Cytopathology. 2008 Oct;19(5):294-302. doi: 10.1111/j.1365-2303.2007.00528.x. Epub 2007 Dec 7.
The prognostic significance of DNA ploidy and the S-phase fraction (SPF) have been extensively studied in breast cancer, but their clinical utility remains controversial. The type of tumour material can substantially influence flow cytometric DNA measurements. Material obtained by fine needle aspiration (FNA) biopsy is very suitable for flow cytometric DNA analysis because it contains a low proportion of non-tumour cells and less debris than tissue samples.
The prognostic significance of DNA ploidy and SPF, determined on FNA samples, was analysed in 770 breast cancer patients, diagnosed between 1992 and 1997. DNA ploidy and SPF were determined at the time of diagnosis as part of the diagnostic work-up. The median follow-up was 90 months. Survival analysis included overall cancer specific survival (OS), disease free survival (DFS) and survival after recurrence (SAR). Other variables included in survival analyses were age, histological grade, histological type, lymph node status and tumour size. Disease free interval and the site of recurrence were also included in SAR analysis.
DNA ploidy and SPF correlated with tumour type, size, lymph node involvement and, especially, tumour grade. In a univariate analysis, both aneuploidy and high SPF were associated with shorter OS, DFS and SAR, but only SPF retained its independent prognostic significance in multivariate analyses. Independent prognostic variables for OS were node status, histological grade, SPF and tumour size. Node status, histological grade and SPF were independent predictors of DFS, while the site of recurrence, SPF, histological grade, disease free interval and age were independent predictors of SAR.
DNA ploidy and SPF can be efficiently and routinely determined on FNA samples. High SPF is independently associated with a worse clinical outcome of patients with breast cancer. Although SPF and histological grade share prognostic information to some degree, SPF provides additional, less subjective prognostic information. The prognostic value of SPF determined on FNA samples could be even more relevant in neoadjuvant settings and for patients not amenable for surgical treatment, when histological grade cannot be assessed.
DNA倍体和S期分数（SPF）在乳腺癌中的预后意义已得到广泛研究，但其临床应用仍存在争议。肿瘤材料的类型会对流式细胞术DNA测量产生重大影响。通过细针穿刺（FNA）活检获得的材料非常适合进行流式细胞术DNA分析，因为与组织样本相比，它所含的非肿瘤细胞比例较低且碎片较少。
对1992年至1997年间确诊的770例乳腺癌患者，分析了FNA样本中DNA倍体和SPF的预后意义。在诊断时测定DNA倍体和SPF，作为诊断检查的一部分。中位随访时间为90个月。生存分析包括总体癌症特异性生存（OS）、无病生存（DFS）和复发后生存（SAR）。生存分析中纳入的其他变量包括年龄、组织学分级、组织学类型、淋巴结状态和肿瘤大小。无病间期和复发部位也纳入SAR分析。
DNA倍体和SPF与肿瘤类型、大小、淋巴结受累情况相关，尤其是与肿瘤分级相关。在单变量分析中，非整倍体和高SPF均与较短的OS、DFS和SAR相关，但在多变量分析中只有SPF保留了其独立的预后意义。OS的独立预后变量为淋巴结状态、组织学分级、SPF和肿瘤大小。淋巴结状态、组织学分级和SPF是DFS的独立预测因素，而复发部位、SPF、组织学分级、无病间期和年龄是SAR的独立预测因素。
可在FNA样本上高效且常规地测定DNA倍体和SPF。高SPF与乳腺癌患者较差的临床结局独立相关。尽管SPF和组织学分级在一定程度上共享预后信息，但SPF提供了额外的、主观性较低的预后信息。在新辅助治疗环境中以及对于无法评估组织学分级的不适合手术治疗的患者，FNA样本中测定的SPF的预后价值可能更具相关性。
