Thaiwong Tuddow, Cirillo Juliana V, Heller Jane, Kiupel Matti
Veterinary Diagnostic Laboratory, College of Veterinary Medicine, Michigan State University, Lansing, MI, United States.
Departamento de Patologia, Facultad de Medicina Veterinaria y Zootecnia, Universidade de São Paulo, São Paulo, Brazil.
Front Vet Sci. 2022 Feb 14;9:815658. doi: 10.3389/fvets.2022.815658. eCollection 2022.
Detection of metastatic mast cell tumors (MCTs) in lymph nodes is a critical factor for treatment, prognosis, and clinical management. Presence/absence of mast cells in the lymph nodes cannot be used as a sole parameter to determine metastasis due to the inability to differentiate neoplastic from non-neoplastic/inflammatory mast cells. While cytologic and histopathologic classifications for assessment of metastatic MCTs based on the numbers and distribution of mast cells have been developed, inconsistency between the clinical interpretation of these grading schemes and actual metastatic status occurs. The aim of this study is to identify a novel diagnostic tool to accurately predict overt metastatic mast cell tumors in lymph nodes. We investigated the possibility of using RT-qPCR to detect mRNA expression of mast cell-specific genes in lymph nodes with different stages of MCT metastatic classification. We are able to establish a highly sensitive and discriminating RT-qPCR measuring Carboxy peptidase A3 (CPA3) and tryptase mRNA expression and identify the cut-off values with high sensitivity and specificity for overt metastatic MCTs in lymph nodes. An area of future interest would be to expand our analysis of the extent to which cut-off values for these markers in correctly identifying disease status, as well as predicting clinical outcomes and survival times. This would offer valuable information regarding the practical applicability of this technique and may enable us to improve our standards of detection metastasis, including possibility of molecular analysis of cytologic specimens obtained from suspicious nodes subjected to surgical excision.
检测淋巴结中的转移性肥大细胞瘤（MCTs）是治疗、预后及临床管理的关键因素。由于无法区分肿瘤性肥大细胞与非肿瘤性/炎性肥大细胞，淋巴结中肥大细胞的有无不能作为判断转移的唯一参数。虽然已经制定了基于肥大细胞数量和分布来评估转移性MCTs的细胞学和组织病理学分类方法，但这些分级方案的临床解读与实际转移状态之间仍存在不一致。本研究的目的是确定一种新型诊断工具，以准确预测淋巴结中明显的转移性肥大细胞瘤。我们研究了使用逆转录定量聚合酶链反应（RT-qPCR）检测不同MCT转移分类阶段淋巴结中肥大细胞特异性基因mRNA表达的可能性。我们能够建立一种高度灵敏且具有区分能力的RT-qPCR方法，用于检测羧肽酶A3（CPA3）和类胰蛋白酶的mRNA表达，并确定对淋巴结中明显转移性MCTs具有高灵敏度和特异性的临界值。未来感兴趣的一个领域是扩大我们的分析范围，即这些标志物的临界值在正确识别疾病状态、预测临床结果和生存时间方面的程度。这将提供有关该技术实际适用性的有价值信息，并可能使我们提高转移检测标准，包括对从接受手术切除的可疑淋巴结获取的细胞学标本进行分子分析的可能性。
