Alì Greta, Boldrini Laura, Lucchi Marco, Mussi Alfredo, Corsi Valentina, Fontanini Gabriella
Division of Pathological Anatomy, Department of Surgery, University of Pisa, Pisa, Italy.
J Thorac Oncol. 2009 Mar;4(3):348-54. doi: 10.1097/JTO.0b013e3181989ddb.
Malignant pleural mesothelioma is a highly aggressive neoplasm with an incidence that is increasing world-wide. Mast cells are part of the innate immune system and have been associated with different solid tumors, but there is controversy surrounding their pro- and antitumorigenic effects in cancers. There are two subsets of human mast cells, resulting from the expression of different enzymes: tryptase positive mast cells and chymase positive mast cells. The purpose of this study was to determine the presence and prognostic significance of tumor infiltrating mast cells in mesothelioma.
Tryptase and chymase mast cell counts were determined by immunohistochemistry in 60 patients with mesothelioma. All pathologic samples were from patients who underwent treatment with intrapleural preoperative interleukin-2 (18 x 10(6) IU/d for 3 days). After one day of recovery, patients underwent surgery. Pleural samples were also immunostained for CD34 to evaluate microvessel count.
High tryptase mast cells counts were found in the majority (73.3%) of the cases studied, and the results were significantly associated with both overall survival (p = 0.02) and time to progression (p = 0.01). This finding was confirmed using multivariate analysis: a higher tryptase mast cells count emerged as an independent favorable prognostic factor (p = 0.02). However, tryptase mast cells count did not show significant correlation with microvessel count.
These results suggest that tumor infiltrating tryptase mast cells, after interleukin-2 preoperative induction therapy, predict improved clinical outcome in patients with malignant pleural mesothelioma, and highlight the critical role of the local inflammatory response in mesothelioma cancer progression.
恶性胸膜间皮瘤是一种侵袭性很强的肿瘤,其发病率在全球范围内呈上升趋势。肥大细胞是固有免疫系统的一部分,与不同的实体瘤有关,但它们在癌症中的促肿瘤和抗肿瘤作用存在争议。人类肥大细胞有两个亚群,由不同酶的表达产生:类胰蛋白酶阳性肥大细胞和糜蛋白酶阳性肥大细胞。本研究的目的是确定间皮瘤中肿瘤浸润肥大细胞的存在及其预后意义。
通过免疫组织化学法测定60例间皮瘤患者的类胰蛋白酶和糜蛋白酶肥大细胞计数。所有病理样本均来自接受术前胸膜内注射白细胞介素-2(18×10⁶IU/d,共3天)治疗的患者。恢复一天后,患者接受手术。胸膜样本也进行CD34免疫染色以评估微血管计数。
在大多数(73.3%)研究病例中发现类胰蛋白酶肥大细胞计数较高,结果与总生存期(p = 0.02)和疾病进展时间(p = 0.01)均显著相关。多因素分析证实了这一发现:较高的类胰蛋白酶肥大细胞计数是一个独立的有利预后因素(p = 0.02)。然而,类胰蛋白酶肥大细胞计数与微血管计数无显著相关性。
这些结果表明,在术前白细胞介素-2诱导治疗后,肿瘤浸润的类胰蛋白酶肥大细胞可预测恶性胸膜间皮瘤患者的临床结局改善,并突出了局部炎症反应在间皮瘤癌症进展中的关键作用。