Department of Drug Discovery Medicine, Medical Innovation Center, Kyoto University Graduate School of Medicine, Sakyo-ku-Yoshida-Konoe-cho, Kyoto, 606-8501, Japan.
Clinical Laboratory, Osaka-Fu Saiseikai Ibaraki Hospital, 2-1-45 Mitsukeyama, Ibaraki, Osaka, 567-0035, Japan.
Sci Rep. 2022 Nov 2;12(1):18519. doi: 10.1038/s41598-022-20334-0.
Diagnostic markers of malignant mesothelioma (MM) have been extensively investigated. Immunohistochemistry (IHC) markers, such as calretinin, have been used for pathologic diagnosis. However, more diagnostic markers are required to improve the specificity and sensitivity of pathologic diagnosis. This study proposed two proteins as diagnostic markers for epithelioid MM. One is RhoA, an MM mutation-susceptible locus-derived protein, and another is vigilin, a lung small cell carcinoma marker. IHC was performed using 93 MM (epithelioid, 71 cases; sarcomatoid, 13 cases; and biphasic, 9 cases), 64 lung adenocarcinoma (LAC), 60 lung squamous cell carcinoma (LSC), and 14 normal mesothelial (NM) tissues. The majority of epithelioid MM cases were positive for both RhoA and vigilin, whereas both IHCs showed lower stainability in biphasic and sarcomatoid MM. Besides, both IHCs showed significantly higher stainability for RhoA and vigilin in epithelioid MM than in LAC and LSC (p < 0.05). Chi-square tests showed that both RhoA and vigilin IHC positive rate in epithelioid MM was not significantly different from that of calretinin (p > 0.05). In the differential diagnosis of MM from lung cancer, the accuracy and specificity of RhoA, vigilin, and calretinin staining were almost equivalent. Further, H-score test showed that there was no significant difference between RhoA versus calretinin and vigilin versus calretinin in IHC positivity in epithelioid MM (p > 0.05). In conclusion, RhoA and vigilin may be candidates for immunohistochemical markers for epithelioid MM.
恶性间皮瘤（MM）的诊断标志物已得到广泛研究。免疫组织化学（IHC）标志物，如钙视网膜蛋白，已用于病理诊断。然而，需要更多的诊断标志物来提高病理诊断的特异性和敏感性。本研究提出了两种作为上皮性 MM 诊断标志物的蛋白质。一种是 RhoA，一种是 MM 突变易感基因座衍生蛋白，另一种是vigilin，一种肺小细胞癌标志物。使用 93 例 MM（上皮型，71 例；肉瘤样型，13 例；双相型，9 例）、64 例肺腺癌（LAC）、60 例肺鳞癌（LSC）和 14 例正常间皮（NM）组织进行了 IHC。大多数上皮性 MM 病例 RhoA 和 vigilin 均为阳性，而双相型和肉瘤样型 MM 的两种 IHC 染色均较低。此外，RhoA 和 vigilin 的 IHC 在上皮性 MM 中的染色强度均显著高于 LAC 和 LSC（p<0.05）。卡方检验显示，RhoA 和 vigilin 的 IHC 在上皮性 MM 中的阳性率与 calretinin 无显著差异（p>0.05）。在 MM 与肺癌的鉴别诊断中，RhoA、vigilin 和 calretinin 染色的准确性和特异性几乎相当。进一步的 H 评分检验显示，RhoA 与 calretinin 以及 vigilin 与 calretinin 在上皮性 MM 的 IHC 阳性率方面无显著差异（p>0.05）。总之，RhoA 和 vigilin 可能是上皮性 MM 的免疫组织化学标志物候选物。
