Russo Antonio, Corsale Simona, Agnese Valentina, Macaluso Marcella, Cascio Sandra, Bruno Loredana, Surmacz Eva, Dardanoni Gabriella, Valerio Maria Rosaria, Vieni Salvatore, Restivo Salvatore, Fulfaro Fabio, Tomasino Rosa Maria, Gebbia Nicola, Bazan Viviana
Section and Oncology, Department of Oncology, Università di Palermo, Palermo, Italy.
J Cell Physiol. 2006 Jan;206(1):181-8. doi: 10.1002/jcp.20447.
To prospectively evaluate the prognostic significance of TP53, H-, K-, and N-Ras mutations, DNA-ploidy and S-phase fraction (SPF) in patients affected by locally advanced laryngeal squamous cell carcinoma (LSCC). Eight-one patients (median follow-up was 71 months) who underwent resective surgery for primary operable locally advanced LSCC were analyzed. Tumor DNA was screened for mutational analysis by PCR/SSCP and sequencing. DNA-ploidy and SPF were performed by flow cytometric analyses. Thirty-six patients (44%) had, at least, a mutation in the TP53 gene. Of them, 22% (8/36) had double mutations and 3% (1/36) had triple mutations. In total, 46 TP53 mutations were observed. The majority (41%) of these occur in exon 5 (19/46), while the mutations in exons 6, 7, and 8 were represented in 14, 7, and 6 patients, respectively (31%, 15%, and 16%). Five LSCC patients (6%) showed a mutation in H-Ras gene. Sixty-three percent of the cases (51/81) were DNA aneuploidy, 14% of these (7/51) were multiclonal. Thirty-nine patients (48%) had an high SPF value. At Univariate analysis, the DNA aneuploidy, high SPF (>15.1%), TP53 mutations and, in particular, the mutations that occur in exons 5 and 8 were significantly related to quicker disease relapse and short OS. At Multivariate analysis, the major significant predictors for both disease relapse and death were high SPF and any TP53 mutations. While histological grade G3 was an independent factor only for relapse. In conclusions, any TP53 mutations and high SPF are important biological indicators to predict the outcome of LSCC patients.
前瞻性评估TP53、H-Ras、K-Ras和N-Ras基因突变、DNA倍体及S期分数（SPF）在局部晚期喉鳞状细胞癌（LSCC）患者中的预后意义。分析了81例接受原发性可手术局部晚期LSCC切除手术的患者（中位随访时间为71个月）。通过PCR/SSCP和测序对肿瘤DNA进行突变分析筛查。通过流式细胞术分析进行DNA倍体和SPF检测。36例患者（44%）至少存在TP53基因的一个突变。其中，22%（8/36）有双重突变，3%（1/36）有三重突变。共观察到46个TP53突变。其中大多数（41%）发生在外显子5（19/46），而外显子6、7和8中的突变分别见于14、7和6例患者（31%、15%和16%）。5例LSCC患者（6%）显示H-Ras基因有突变。63%的病例（51/81）为DNA非整倍体，其中14%（7/51）为多克隆性。39例患者（48%）的SPF值较高。单因素分析显示，DNA非整倍体、高SPF（>15.1%）、TP53突变，尤其是外显子5和8中发生的突变与疾病更快复发和较短总生存期显著相关。多因素分析显示，疾病复发和死亡的主要显著预测因素是高SPF和任何TP53突变。而组织学分级G3仅是复发的独立因素。总之，任何TP53突变和高SPF都是预测LSCC患者预后的重要生物学指标。
