Gallo O, Bianchi S, Giovannucci-Uzzielli M L, Santoro R, Lenzi S, Salimbeni C, Abbruzzese M, Alajmo E
Institute of Otolaryngology-Head & Neck Surgery, University of Florence, Italy.
Br J Cancer. 1995 May;71(5):1008-12. doi: 10.1038/bjc.1995.194.
In this study, we analysed immunocytochemically p53 expression in first primary and second primary cancers from 25 head and neck cancer patients (HNCPs) with multiple malignancies in comparison with oncoprotein expression in tumour tissues from 25 historical HNCP controls with single cancer in a match-paired analysis. Moreover, we investigated bleomycin-induced chromosome fragility in both groups of HNCPs and in 21 additional healthy controls. Thirty-nine out of 75 tumour specimens analysed (52%) showed positive p53 immunostaining. Eleven out of 25 (44%) from single cancer patients and 28 out of 50 (56%) tumours from HNCPs with multiple malignancies were p53 positive. In the group of multiple primary cancers, nine patients (36%) showed positive staining of both first and second primaries, whereas six (24%) had positive labelling of first primary cancer but not of the subsequent second primary, four (16%) patient showed p53 expression only in the second primary cancer and six (24%) patients showed no p53 immunoreactivity in both tumours. Chromosomal analysis demonstrated a higher sensitivity to clastogens of HNCPs with multiple tumours than of HNCPs with a single cancer (P < 0.01), and a significant correlation between chromosome fragility and p53 overexpression (P < 0.01) only in HNCPs with multiple malignancies more than in those with single head and neck cancer (P = 0.11). Moreover, we found that patients with p53-positive staining of both first and second primaries showed a statistically significant higher mutagen sensitivity than those with a single p53 immunoreactive tumour or those in whom both cancers were p53 negative (P < 0.01). Our data suggest that subjects with increased susceptibility to carcingogens after exposure to tobacco or alcohol are at higher risk for multiple cancers in which one of the most common genetic events is aberrant p53 expression.
在本研究中，我们采用配对分析，对25例患有多种恶性肿瘤的头颈部癌症患者（HNCPs）的第一原发性和第二原发性癌症中的p53表达进行了免疫细胞化学分析，并与25例患有单一癌症的头颈部癌症历史对照患者肿瘤组织中的癌蛋白表达进行了比较。此外，我们还研究了两组HNCPs以及另外21名健康对照者中博来霉素诱导的染色体脆性。在分析的75个肿瘤标本中，39个（52%）显示p53免疫染色呈阳性。25名单一癌症患者中有11个（44%）肿瘤以及50例患有多种恶性肿瘤的HNCPs中有28个（56%）肿瘤p53呈阳性。在多原发性癌症组中，9例患者（36%）的第一原发性和第二原发性癌症均显示阳性染色，而6例（24%）患者的第一原发性癌症呈阳性标记，但随后的第二原发性癌症未呈阳性，4例（16%）患者仅在第二原发性癌症中显示p53表达，6例（24%）患者的两种肿瘤均未显示p53免疫反应性。染色体分析表明，患有多种肿瘤的HNCPs比患有单一癌症的HNCPs对致裂剂的敏感性更高（P<0.01），并且仅在患有多种恶性肿瘤的HNCPs中，染色体脆性与p53过表达之间存在显著相关性（P<0.01），而在患有单一头颈部癌症的患者中相关性不显著（P = 0.11）。此外，我们发现第一原发性和第二原发性癌症p53染色均呈阳性的患者比那些只有一个p53免疫反应性肿瘤的患者或两种癌症p53均为阴性的患者具有统计学上显著更高的诱变敏感性（P<0.01）。我们的数据表明，接触烟草或酒精后对致癌物易感性增加的个体患多种癌症的风险更高，其中最常见的基因事件之一是p53表达异常。
