Abstract：
BACKGROUND: Claudin-4 has been described as a highly sensitive immunocytochemical marker for detection of metastatic carcinoma cells in effusion cytology specimens. This study aims to challenge the performance of claudin-4 in different types of malignancies and low cellularity specimens, by comparison with other markers in a large cohort of carcinomatous effusion specimens.
METHODS: Cell block preparations from peritoneal and pleural fluid specimens were retrieved, with malignant (carcinoma) diagnoses confirmed by review of hospital diagnosis code and pathology reports. Claudin-4, BerEP4, CEA, and MOC31 immunocytochemistry were performed and scored by expression proportion and intensity. Tumor cellularity was assessed for subgroup analysis of low cellularity specimens.
RESULTS: Totally 147 specimens (70 pleural, 77 peritoneal) of 68 lung, 62 breast, 9 gynecological, and 7 gastrointestinal carcinomas were retrieved. The average proportion expression of claudin-4 was highest (89.6%, vs. CEA 40.5%, BerEp4 18.6%, MOC31 16.8%) and the percentage of strong expression was highest for claudin-4 (72.1%). Expression levels of claudin-4 were consistently higher than other markers in subgroups of all primary sites. The difference was more significant for low cellularity specimens. High (≥50%) proportion expression was seen for 96.61% of cases for claudin-4 (vs. BerEp4 8.77%, CEA 46.55%, MOC31 8.77%, p < 0.001). These factors contributed to a low concordance between claudin-4 and BerEp4, CEA and MOC31 (K = 0.010-0.043).
CONCLUSIONS: Claudin-4 is more sensitive than CEA, BerEp4 and MOC31, suitable for low cellularity specimens of most types of metastatic carcinoma and is a robust immunocytochemical marker for carcinoma that can be used solitarily.
METHODS: Cell block preparations from peritoneal and pleural fluid specimens were retrieved, with malignant (carcinoma) diagnoses confirmed by review of hospital diagnosis code and pathology reports. Claudin-4, BerEP4, CEA, and MOC31 immunocytochemistry were performed and scored by expression proportion and intensity. Tumor cellularity was assessed for subgroup analysis of low cellularity specimens.
RESULTS: Totally 147 specimens (70 pleural, 77 peritoneal) of 68 lung, 62 breast, 9 gynecological, and 7 gastrointestinal carcinomas were retrieved. The average proportion expression of claudin-4 was highest (89.6%, vs. CEA 40.5%, BerEp4 18.6%, MOC31 16.8%) and the percentage of strong expression was highest for claudin-4 (72.1%). Expression levels of claudin-4 were consistently higher than other markers in subgroups of all primary sites. The difference was more significant for low cellularity specimens. High (≥50%) proportion expression was seen for 96.61% of cases for claudin-4 (vs. BerEp4 8.77%, CEA 46.55%, MOC31 8.77%, p < 0.001). These factors contributed to a low concordance between claudin-4 and BerEp4, CEA and MOC31 (K = 0.010-0.043).
CONCLUSIONS: Claudin-4 is more sensitive than CEA, BerEp4 and MOC31, suitable for low cellularity specimens of most types of metastatic carcinoma and is a robust immunocytochemical marker for carcinoma that can be used solitarily.
摘要：
背景：已将Claudin-4描述为一种高度敏感的免疫细胞化学标记，用于检测积液细胞学标本中的转移性癌细胞。这项研究旨在挑战claudin-4在不同类型的恶性肿瘤和低细胞性标本中的表现，通过与大量癌性积液标本中的其他标志物进行比较。
方法：从腹腔和胸腔积液标本中提取细胞块制剂，通过检查医院诊断代码和病理报告证实的恶性（癌）诊断。Claudin-4,BerEP4,CEA,和MOC31进行免疫细胞化学，并通过表达比例和强度进行评分。对低细胞性标本的亚组分析评估了肿瘤细胞性。
结果：共147个标本（70个胸膜，77腹膜）68肺，62乳房，9妇科，并检索到7例胃肠道癌。claudin-4的平均表达比例最高(89.6%,vs.CEA40.5%,Berep418.6%,MOC3116.8％），claudin-4的强表达百分比最高（72.1％）。在所有主要位点的亚组中，claudin-4的表达水平始终高于其他标志物。对于低细胞含量的标本，差异更为显着。在96.61%的claudin-4病例中观察到高（≥50%）比例表达（与Berep48.77%，CEA46.55%，MOC318.77%，p<0.001)。这些因素导致claudin-4与Berep4，CEA和MOC31之间的一致性较低（K=0.010-0.043）。
结论：Claudin-4比CEA更敏感，BerEp4和MOC31，适用于大多数类型的转移性癌的低细胞数量标本，是癌症的强大免疫细胞化学标记，可单独使用。
方法：从腹腔和胸腔积液标本中提取细胞块制剂，通过检查医院诊断代码和病理报告证实的恶性（癌）诊断。Claudin-4,BerEP4,CEA,和MOC31进行免疫细胞化学，并通过表达比例和强度进行评分。对低细胞性标本的亚组分析评估了肿瘤细胞性。
结果：共147个标本（70个胸膜，77腹膜）68肺，62乳房，9妇科，并检索到7例胃肠道癌。claudin-4的平均表达比例最高(89.6%,vs.CEA40.5%,Berep418.6%,MOC3116.8％），claudin-4的强表达百分比最高（72.1％）。在所有主要位点的亚组中，claudin-4的表达水平始终高于其他标志物。对于低细胞含量的标本，差异更为显着。在96.61%的claudin-4病例中观察到高（≥50%）比例表达（与Berep48.77%，CEA46.55%，MOC318.77%，p<0.001)。这些因素导致claudin-4与Berep4，CEA和MOC31之间的一致性较低（K=0.010-0.043）。
结论：Claudin-4比CEA更敏感，BerEp4和MOC31，适用于大多数类型的转移性癌的低细胞数量标本，是癌症的强大免疫细胞化学标记，可单独使用。
