Bilde Anders, von Buchwald Christian, Dabelsteen Erik, Therkildsen Marianne Hamilton, Dabelsteen Sally
Department of Otolaryngology-Head & Neck Surgery, Copenhagen University Hospital, Copenhagen, Denmark.
J Oral Pathol Med. 2009 Jan;38(1):72-8. doi: 10.1111/j.1600-0714.2008.00715.x.
Local or regional lymph node recurrence is the most common pattern of treatment failure in oral squamous cell carcinoma (SCC). The local recurrence rate is 30% even when the surgical resection margin is diagnosed as tumour free. Accumulation of genetic changes in histologically normal epithelium in the surgical resection margin may explain the local recurrence rate. The purpose of this study is to investigate the presence of senescence markers, which may represent early malignant changes in the margin that in routine pathological evaluations are classified as histologically normal.
Formalin-fixed, paraffin-embedded surgical specimens from 16 consecutive patients with oral SCC and a clear surgical margin were obtained. The margin was analysed by immunohistochemistry for p53, p16, Chk2, Laminin-5 and glycosylated oncofetal fibronectin.
Two patterns of p53 expression were found in the histologically normal epithelium in the surgical resection margin. One was characterized by no protein expression in the majority of cells, except for small clusters of basal and parabasal cells with nuclear staining. The other was characterized by p53 expression in the nuclei of most basal cells. The expression of p16 was confined to small groups of cells in the basal cell layer whereas Chk2 was only seen in one case. Upregulation of the stromal proteins, Laminin-5 or glycosylated oncofetal fibronectin, was only seen at regions of invasion.
Small groups of cells expressing p53 and p16 were found in the surgical resection margin that appeared to be histologically normal and may represent early malignant changes.
局部或区域淋巴结复发是口腔鳞状细胞癌(SCC)最常见的治疗失败模式。即使手术切缘诊断为无肿瘤,局部复发率仍为30%。手术切缘组织学正常上皮中基因变化的积累可能解释了局部复发率。本研究的目的是调查衰老标志物的存在情况,这些标志物可能代表切缘处的早期恶性变化,而在常规病理评估中这些切缘被归类为组织学正常。
获取16例连续的口腔SCC患者且手术切缘清晰的福尔马林固定、石蜡包埋手术标本。通过免疫组织化学分析切缘的p53、p16、Chk2、层粘连蛋白-5和糖基化癌胚纤维连接蛋白。
在手术切缘组织学正常上皮中发现了两种p53表达模式。一种模式的特征是大多数细胞中无蛋白表达,除了少数具有核染色的基底细胞和副基底细胞小簇。另一种模式的特征是大多数基底细胞核中p53表达。p16的表达局限于基底细胞层中的小细胞群,而Chk2仅在1例中可见。基质蛋白层粘连蛋白-5或糖基化癌胚纤维连接蛋白的上调仅在浸润区域可见。
在看似组织学正常的手术切缘中发现了表达p53和p16的小细胞群,可能代表早期恶性变化。