Balancin Marcelo Luiz, Baldavira Camila Machado, Prieto Tabatha Gutierrez, Machado-Rugolo Juliana, Farhat Cecília, Assato Aline Kawassaki, Velosa Ana Paula Pereira, Teodoro Walcy Rosolia, Ab'Saber Alexandre Muxfeldt, Takagaki Teresa Yae, Capelozzi Vera Luiza
Laboratory of Genomics and Histomorphometry, Department of Pathology, University of São Paulo Medical School (USP), São Paulo, Brazil.
Health Technology Assessment Center (NATS), Clinical Hospital (HCFMB), Medical School of São Paulo State University (UNESP), Botucatu, Brazil.
Front Med (Lausanne). 2022 Apr 13;9:871202. doi: 10.3389/fmed.2022.871202. eCollection 2022.
Malignant pleural mesotheliomas (MM) are known for their heterogenous histology and clinical behavior. MM histology reveals three major tumor cell populations: epithelioid, sarcomatoid, and biphasic. Using a dissecting approach, we showed that histochemical gradients help us better understand tumor heterogeneity and reconsider its histologic classifications. We also showed that this method to characterize MM tumor cell populations provides a better understanding of the underlying mechanisms for invasion and disease progression.
In a cohort of 87 patients with surgically excised MM, we used hematoxylin and eosin to characterize tumor cell populations and Movat's pentachrome staining to dissect the ECM matrisome. Next, we developed a computerized semi-assisted protocol to quantify and reconstruct the ECM in 3D and examined the clinical association between the matricellular factors and patient outcome.
Epithelioid cells had a higher matrix composition of elastin and fibrin, whereas, in the sarcomatoid type, hyaluronic acid and total collagen were most prevalent. The 3D reconstruction exposed the collagen I and III that form channels surrounding the neoplastic cell blocks. The estimated volume of the two collagen fractions was 14% of the total volume, consistent with the median estimated area of total collagen (12.05 mm) for epithelioid MM.
Differential patterns in matricellular phenotypes in MM could be used in translational studies to improve patient outcome. More importantly, our data raise the possibility that cancer cells can use the matrisome for disease expansion and could be effectively targeted by anti-collagen, anti-elastin, and/or anti-hyaluronic acid therapies.
恶性胸膜间皮瘤（MM）以其组织学和临床行为的异质性而闻名。MM组织学显示出三种主要的肿瘤细胞群体：上皮样、肉瘤样和双向性。通过解剖学方法，我们发现组织化学梯度有助于我们更好地理解肿瘤异质性并重新考虑其组织学分类。我们还表明，这种表征MM肿瘤细胞群体的方法能更好地理解侵袭和疾病进展的潜在机制。
在一组87例手术切除的MM患者中，我们使用苏木精和伊红来表征肿瘤细胞群体，并使用莫瓦特五色染色法剖析细胞外基质（ECM）基质组。接下来，我们开发了一种计算机化的半辅助方案来定量和三维重建ECM，并研究基质细胞因子与患者预后之间的临床关联。
上皮样细胞的弹性蛋白和纤维蛋白基质成分较高，而在肉瘤样类型中，透明质酸和总胶原蛋白最为普遍。三维重建显示了I型和III型胶原蛋白形成围绕肿瘤细胞块的通道。这两种胶原蛋白组分的估计体积占总体积的14%，与上皮样MM的总胶原蛋白估计面积中位数（12.05平方毫米）一致。
MM中基质细胞表型的差异模式可用于转化研究以改善患者预后。更重要的是，我们的数据提出了癌细胞可以利用基质组进行疾病扩展的可能性，并且可能通过抗胶原蛋白、抗弹性蛋白和/或抗透明质酸疗法有效靶向。
