Mori Kazuhiko, Suzuki Tomohiro, Uozaki Hiroshi, Nakanishi Hayao, Ueda Tetsuya, Matsuno Yoshihiro, Kodera Yasuhiro, Sakamoto Hiromi, Yamamoto Nobuko, Sasako Mitsuru, Kaminishi Michio, Sasaki Hiroki
Department of Gastrointestinal Surgery, University of Tokyo Graduate School of Medicine, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-8655, Japan.
Ann Surg Oncol. 2007 May;14(5):1694-702. doi: 10.1245/s10434-006-9321-4. Epub 2007 Feb 9.
Peritoneal cytology is an important prognostic factor of gastric cancer. However, peritoneal cytology requires great skill, which may explain its low prevalence. A reverse transcriptase-polymerase chain reaction-based assay with multiple marker genes or immunocytochemistry was assessed as an alternative method of gathering the same kind of data as cytology.
Peritoneal washings from 179 patients with gastric cancer were analyzed by multiplex reverse transcriptase-polymerase chain reaction with 10 marker genes and subsequent hybridization to a customized oligo-nucleotide array. Results with this assay were either validated as a prognostic factor or confirmed by demonstrating the presence of cancer cells by immunocytochemical cytology.
Only 1 (2.2%) of 44 disease-free cases was shown to be positive by the microarray assay, whereas 13 (93%) of 14 conventional cytology-positive cases were found to be positive. This assay further detected approximately one-third of cytology-negative patients either with peritoneal recurrence (7 of 20, 35%) or with non-peritoneal recurrence (6 of 22, 27%). A high concordance between the microarray assay and immunocytochemical cytology with five antibodies against CK20, FABP1, MUC2, TFF1, and MASPIN was confirmed. The clinical outcome of the microarray assay-positive cases was poor, as was that of the cytology-positive cases.
Our assay, though time-consuming and requiring special equipment, demonstrated a specificity and sensitivity equal to or better than cytology in our institutes. The minimal free peritoneal cancer cells detected by the microarray assay may provide the same clinical information as larger amounts of cancer cells for patients with gastric cancer. An anti-MASPIN antibody may be helpful in peritoneal cytology of gastric cancer.
腹膜细胞学检查是胃癌的一项重要预后因素。然而,腹膜细胞学检查需要很高的技术水平,这可能是其普及率较低的原因。基于逆转录聚合酶链反应的多标记基因检测法或免疫细胞化学方法被评估为一种可替代的方法,用于获取与细胞学检查相同类型的数据。
采用针对10个标记基因的多重逆转录聚合酶链反应,对179例胃癌患者的腹腔灌洗液进行分析,并随后与定制的寡核苷酸阵列进行杂交。该检测结果作为预后因素进行验证,或通过免疫细胞化学细胞学方法证实癌细胞的存在来确认。
在44例无病病例中,只有1例(2.2%)通过微阵列检测呈阳性,而在14例传统细胞学检查阳性的病例中,有13例(93%)被发现呈阳性。该检测还进一步检测出约三分之一细胞学检查阴性的患者,这些患者要么发生腹膜复发(20例中的7例,35%),要么发生非腹膜复发(22例中的6例,27%)。证实了微阵列检测与针对细胞角蛋白20、脂肪酸结合蛋白1、粘蛋白2、三叶因子1和激肽释放酶原激活物抑制剂1的五种抗体的免疫细胞化学细胞学检查之间具有高度一致性。微阵列检测阳性病例的临床结局较差,细胞学检查阳性病例的临床结局也较差。
我们的检测方法虽然耗时且需要特殊设备,但在我们的研究所中显示出与细胞学检查相当或更好的特异性和敏感性。微阵列检测所检测到的微量游离腹膜癌细胞可能为胃癌患者提供与大量癌细胞相同的临床信息。抗激肽释放酶原激活物抑制剂1抗体可能有助于胃癌的腹膜细胞学检查。