Pierssens Damiana D C G, Borgemeester Maarten C, van der Heijden Stijn J H, Peutz-Kootstra Carine J, Ruland Andrea M, Haesevoets Annick M, Kessler Peter A W H, Kremer Bernd, Speel Ernst-Jan M
Department of Oral and Craniomaxillofacial Surgery, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
Department of Otorhinolaryngology, Head & Neck Surgery, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
Oral Oncol. 2017 Mar;66:14-21. doi: 10.1016/j.oraloncology.2016.12.029. Epub 2017 Jan 6.
The local recurrence rate in oral squamous cell cancer (OSCC) hardly decreases. This is partly due to the presence of (pre)malignant cells in the remaining tissue after resection, that may lead to the development of a new tumor in time. Detection of histologically (pre)malignant cells in the tumor resection margins should predict these patients at risk for recurrence, however this appears to be difficult in routine practice. Purpose of this study was to apply easy-to-use molecular tests for more accurate detection of (pre)malignant cells in histopathologically tumor-free margins, to improve diagnosis of patients at risk.
42 patients with firstly diagnosed, radically resected primary OSCC with histopathologically confirmed tumor-free resection margins (treated between 1994 and 2003) were included. Inclusion criteria comprised of follow-up ⩾5years, and radical surgery without postoperative treatment. Formalin-fixed paraffine-embedded tissue sections of 42 tumors, 290 resection margins, and 11 recurrences were subjected to fluorescence in situ hybridization (FISH) to examine chromosome 1 and 7 copy number variations (CNV), and to p53 immunohistochemistry (IHC).
11 out of the 42 patients developed a local recurrence within 5years. FISH analysis showed that nine of eleven recurrences exhibited CI in at least one of the resection margins (p=0.008). P53 overexpression and routine histopathologic classification were not correlated with recurrent disease. The presence of CI in the resection margins revealed a significantly worse progression-free survival (log-rank p=0.012).
CI in the resection margins of OSCC can reliably identify patients at risk for developing a local recurrence.
口腔鳞状细胞癌（OSCC）的局部复发率几乎没有下降。部分原因是切除后剩余组织中存在（癌前）恶性细胞，这可能会导致新肿瘤的发生。在肿瘤切除边缘检测组织学上的（癌前）恶性细胞应能预测这些有复发风险的患者，但在常规实践中这似乎很困难。本研究的目的是应用易于使用的分子检测方法，更准确地检测组织病理学上无肿瘤边缘的（癌前）恶性细胞，以改善对有风险患者的诊断。
纳入42例首次诊断、根治性切除的原发性OSCC患者，其组织病理学证实切除边缘无肿瘤（1994年至2003年期间接受治疗）。纳入标准包括随访≥5年，以及未进行术后治疗的根治性手术。对42个肿瘤、290个切除边缘和11个复发灶的福尔马林固定石蜡包埋组织切片进行荧光原位杂交（FISH），以检测1号和7号染色体拷贝数变异（CNV），并进行p53免疫组织化学（IHC）检测。
42例患者中有11例在5年内出现局部复发。FISH分析显示，11例复发中有9例在至少一个切除边缘表现出染色体不稳定性（CI）（p = 0.008）。p53过表达和常规组织病理学分类与复发性疾病无关。切除边缘存在CI显示无进展生存期明显更差（对数秩检验p = 0.012）。
OSCC切除边缘的CI能够可靠地识别有发生局部复发风险的患者。
