实时聚合酶链反应增加了对胃癌亚微观腹膜转移的检测，并具有预后意义。
Rt-PCR increases detection of submicroscopic peritoneal metastases in gastric cancer and has prognostic significance.
机构信息
Department of Surgery, Memorial Sloan-Kettering Cancer Center, 275 York Avenue, New York, NY 10021, USA.
出版信息
J Gastrointest Surg. 2012 May;16(5):889-96; discussion 896. doi: 10.1007/s11605-012-1845-2. Epub 2012 Feb 24.
BACKGROUND
Positive peritoneal cytology confers the same prognosis as clinical stage IV disease in gastric cancer. Conventional cytology examination, however, has low sensitivity. We hypothesize that real-time polymerase chain reaction (RT-PCR) may have increased sensitivity and provide more accurate staging information.
METHODS
From February 2007 to April 2009, peritoneal lavage samples were collected prospectively from 156 patients with biopsy-proven gastric cancer undergoing staging laparoscopy. These washings were analyzed by both Papanicolaou staining and RT-PCR for the tumor marker carcinoembryonic antigen (CEA).
RESULTS
Visible peritoneal disease was seen at laparoscopy in 38 patients (LAP+, 24%). Cytology was positive (CYT+) in 23 patients, while RT-PCR was positive (PCR+) in 30. The sensitivity of CYT for the detection of visible disease was 61% compared to 79% for PCR (P = 0.02). No visible peritoneal disease was seen at laparoscopy (LAP-) in 118 (76%) patients. Eight (7%) were CYT+, while 28 (24%) were PCR+. Predictors of PCR positivity included advanced-stage disease (T3-4 vs. T1-2 tumors) and poor pathologic features such as vascular or perineural invasion. Long-term follow-up demonstrated a worse survival of LAP-CYT-PCR+ (P = 0.0003) and LAP-CYT+PCR+ (P = 0.0004) compared to LAP-CYT-PCR- patients. There was no significant difference in survival between CYT-PCR+ and CYT+PCR+ patients. PCR positivity also predicted a higher likelihood of disease recurrence after resection. An R0 resection was performed in 85 LAP- patients (54%): only 1 (1%) was CYT+, while 13 (15%) were PCR+. Of this group, PCR+ demonstrated a worse survival than PCR- patients (P = 0.02). Further analysis showed that, in R0 resection, stage III/IV, CYT- subgroup, PCR+ was associated with a trend towards worse survival (P = 0.09) compared to PCR- patients.
CONCLUSION
RT-PCR for CEA increases the detection of subclinical peritoneal disease and is more sensitive than cytology. Predictors of positive PCR included advanced-stage disease, vascular invasion, and perineural invasion. PCR positivity was associated with increased disease recurrence and decreased survival. Further follow-up is required to determine if PCR positivity alone is an independent predictor of poor survival in gastric cancer.
背景
阳性腹膜细胞学检查与胃癌临床 IV 期疾病具有相同的预后。然而，常规细胞学检查的灵敏度较低。我们假设实时聚合酶链反应（RT-PCR）可能具有更高的灵敏度，并提供更准确的分期信息。
方法
从 2007 年 2 月至 2009 年 4 月，前瞻性收集了 156 例经活检证实的胃癌患者行腹腔镜分期检查时的腹腔灌洗样本。这些洗液通过巴氏染色和 RT-PCR 分析肿瘤标志物癌胚抗原（CEA）。
结果
腹腔镜下可见腹膜疾病 38 例（LAP+，24%）。细胞学阳性（CYT+）23 例，PCR 阳性（PCR+）30 例。CYT 检测肉眼可见疾病的灵敏度为 61%，而 PCR 的灵敏度为 79%（P=0.02）。腹腔镜下未见腹膜疾病（LAP-）118 例（76%）。8 例（7%）为 CYT+，28 例（24%）为 PCR+。PCR 阳性的预测因素包括晚期疾病（T3-4 与 T1-2 肿瘤）和血管或神经周围侵犯等不良病理特征。长期随访显示，LAP-CYT-PCR+（P=0.0003）和 LAP-CYT+PCR+（P=0.0004）患者的生存率明显低于 LAP-CYT-PCR-患者。CYT-PCR+和 CYT+PCR+患者的生存率无显著差异。PCR 阳性也预示着切除后疾病复发的可能性更高。85 例 LAP-患者行 R0 切除术（54%）：仅 1 例（1%）为 CYT+，13 例（15%）为 PCR+。在这一组中，PCR+患者的生存率明显低于 PCR-患者（P=0.02）。进一步分析显示，在 R0 切除、III/IV 期、CYT-亚组中，与 PCR-患者相比，PCR+患者的生存趋势较差（P=0.09）。
结论
CEA 的 RT-PCR 提高了亚临床腹膜疾病的检出率，比细胞学检查更敏感。PCR 阳性的预测因素包括晚期疾病、血管侵犯和神经周围侵犯。PCR 阳性与疾病复发增加和生存率降低有关。需要进一步随访以确定 PCR 阳性是否是胃癌不良生存的独立预测因素。
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