Papadaki H, Finkelstein S D, Kounelis S, Bakker A, Swalsky P A, Kapadia S B
Department of Pathology, University of Pittsburgh Medical Center, PA 15213, USA.
Hum Pathol. 1996 Jun;27(6):567-72. doi: 10.1016/s0046-8177(96)90163-x.
Adenoid cystic carcinoma (ACC) is a malignant tumor of salivary gland origin having a propensity for spread by direct extension or perineural invasion with frequent recurrences. Previous reports have shown that tumor behavior is not always predicted by histological pattern or stage. Little is known of the role of p53 tumor suppressor gene mutation and altered protein expression with respect to ACC pathobiology and recurrence. The authors analyzed a group of 14 ACC specimens (seven primary; seven recurrent) from 13 patients treated between 1987 to 1993. Formalin-fixed, paraffin-embedded specimens were reviewed and subjected to, immunohistochemistry (p53, DO-7, DAKO, Nutley, NJ; and WAF-I, Ab-1, Oncogene Sciences, Uniondale, NY) on 4-microm-thick histological sections as a prelude to p53 genotyping. In one case, sequential material representing primary and recurrent tumor was analyzed. Each tumor specimen was topographically genotyped for p53 point mutational change. Minute tissue samples were removed from unstained sections, polymerase chain reaction (PCR) amplified for p53 exons 5 to 8, and then underwent direct DNA sequencing. Six of seven primary ACCs were p53 immunostain negative. Four of seven recurrent (57%) ACCs were p53 immunopositive. These tumors showed varying degrees of p53 immunopositivity ranging from diffuse, intense staining of most tumor cells (n = 1) to interspersed, strongly positive cells mixed with predominantly p53 immunonegative cells (n = 4). All tumors were WAF-I immunostain negative. Two of the most immunopositive recurrent tumors each manifested a single type of p53 point mutation detected by p53 DNA genotyping (p53 exon 5:codon 175 and p53 exon 6:codon 199). In the case in which both primary and recurrent tumor was available, only the recurrent tumor contained point mutational damage. Negative immunostaining for p53 in primary ACC suggests that p53 mutation is not important in early events involving development of this tumor. In contrast, the frequent presence of p53-positive cells and the detection of point mutations in recurrent ACC suggests that p53 alterations are involved in later stages of tumor progression, important in the phenomenon of ACC recurrence.
腺样囊性癌（ACC）是一种起源于唾液腺的恶性肿瘤，倾向于通过直接蔓延或神经周围浸润扩散，且经常复发。既往报道显示，肿瘤行为并不总是能通过组织学模式或分期来预测。关于p53肿瘤抑制基因突变及蛋白表达改变在ACC病理生物学及复发方面的作用，人们了解甚少。作者分析了1987年至1993年间接受治疗的13例患者的14份ACC标本（7份原发；7份复发）。对福尔马林固定、石蜡包埋的标本进行复查，并在4微米厚的组织切片上进行免疫组织化学检测（p53、DO-7，DAKO公司，新泽西州纳特利；以及WAF-1，Ab-1，癌基因科学公司，纽约州尤宁代尔），作为p53基因分型的前奏。在1例病例中，对代表原发和复发肿瘤的连续材料进行了分析。对每个肿瘤标本进行p53点突变变化的拓扑基因分型。从未染色切片中取出微小组织样本，对p53外显子5至8进行聚合酶链反应（PCR）扩增，然后进行直接DNA测序。7例原发ACC中有6例p53免疫染色阴性。7例复发ACC中有4例（57%）p53免疫阳性。这些肿瘤表现出不同程度的p53免疫阳性，范围从大多数肿瘤细胞弥漫性、强烈染色（n = 1）到散在的、强阳性细胞与主要为p53免疫阴性细胞混合（n = 4）。所有肿瘤WAF-1免疫染色均为阴性。2例免疫阳性最强的复发肿瘤通过p53 DNA基因分型各表现出一种p53点突变（p53外显子5：密码子175和p53外显子6：密码子（199）。在可获得原发和复发肿瘤的病例中，只有复发肿瘤存在点突变损伤。原发ACC中p53免疫染色阴性表明p53突变在该肿瘤发生的早期事件中并不重要。相比之下，复发ACC中频繁出现p53阳性细胞及检测到点突变表明p53改变参与肿瘤进展的后期阶段，对ACC复发现象很重要。
