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Abstract：
BACKGROUND: Tenosynovial giant cell tumor (TGCT) is a monoarticular fibrohistiocytic benign or locally aggressive soft tissue tumor that originates from the synovium of joints, bursae, and tendon sheaths. It has an inflammatory neoplastic nature, with a clinical presentation ranging from pain, swelling, stiffness, and limited range of movement to joint instability and blockage. Its uncommon incidence leads to a poorly understood pathogenesis. Localized forms of TGCT (LTGCT) can cause significant morbidity, interfere with daily patient activities, and decrease the patient\'s quality of life in challenging cases. This study aimed to investigate the immunohistochemical expression of PPARγ (peroxisome proliferator-activated receptor gamma) and P53 in LTGCT to understand the disease better and offer potential therapeutic targets.
METHODS: The study is cross-sectional, in which 27 LTGCT cases were collected from the Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt. Solitary and multiple LTGCT cases retrieved between January 2018 and December 2022 were included, and immunohistochemically stained with anti-PPARγ and P53 antibodies. The TGCT samples were excluded if they were insufficient for sectioning, processing, and interpretation, over-fixed, had process artifacts, or were of the diffuse TGCT type. Scoring of stain expression was performed by ImageJ (National Institutes of Health, Bethesda, MD) analysis using the threshold method and was expressed in percent area/high power field. Clinicopathological correlations were analyzed.
RESULTS: All the 27 collected LTGCT cases were located in the small joints of patients\' hands. Cases with solitary LGTCTs constituted 55.6% (n = 15), while 44.4% (n = 12) had multiple LTGCTs related to one affected site/case (e.g., multiple tumors in one finger). PPARγ was expressed in the cytoplasm of mononuclear and multinucleated tumor cells and foamy histiocytes, while P53 expression was mainly in mononuclear cells\' nuclei. PPARγ significantly correlated with P53 expression (r = 0.9 and P = 0.000). PPARγ (r = 0.4 and P = 0.02) and P53 (r = 0.5 and P = 0.01) were positively correlated with tumor size. Only P53 expression was positively correlated with tumor multiplicity (r = 0.4 and P = 0.03). Using the receiver operating characteristic curve test, the P53 cutoff score detecting the multiplicity of TGCTs was ≥20.5%, with a 75% sensitivity and 80% specificity.
CONCLUSIONS: PPARγ and P53 have a significant role in LTGCT growth, while P53 plays a role in tumor multiplicity. They can be possible targets in LTGCTs unfit for excision.
METHODS: The study is cross-sectional, in which 27 LTGCT cases were collected from the Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt. Solitary and multiple LTGCT cases retrieved between January 2018 and December 2022 were included, and immunohistochemically stained with anti-PPARγ and P53 antibodies. The TGCT samples were excluded if they were insufficient for sectioning, processing, and interpretation, over-fixed, had process artifacts, or were of the diffuse TGCT type. Scoring of stain expression was performed by ImageJ (National Institutes of Health, Bethesda, MD) analysis using the threshold method and was expressed in percent area/high power field. Clinicopathological correlations were analyzed.
RESULTS: All the 27 collected LTGCT cases were located in the small joints of patients\' hands. Cases with solitary LGTCTs constituted 55.6% (n = 15), while 44.4% (n = 12) had multiple LTGCTs related to one affected site/case (e.g., multiple tumors in one finger). PPARγ was expressed in the cytoplasm of mononuclear and multinucleated tumor cells and foamy histiocytes, while P53 expression was mainly in mononuclear cells\' nuclei. PPARγ significantly correlated with P53 expression (r = 0.9 and P = 0.000). PPARγ (r = 0.4 and P = 0.02) and P53 (r = 0.5 and P = 0.01) were positively correlated with tumor size. Only P53 expression was positively correlated with tumor multiplicity (r = 0.4 and P = 0.03). Using the receiver operating characteristic curve test, the P53 cutoff score detecting the multiplicity of TGCTs was ≥20.5%, with a 75% sensitivity and 80% specificity.
CONCLUSIONS: PPARγ and P53 have a significant role in LTGCT growth, while P53 plays a role in tumor multiplicity. They can be possible targets in LTGCTs unfit for excision.
摘要：
背景：滑膜巨细胞瘤（TGCT）是一种起源于关节滑膜的单关节纤维组织细胞良性或局部侵袭性软组织肿瘤，法氏囊,和肌腱鞘.它具有炎症性肿瘤性质，临床表现包括疼痛，肿胀,刚度,关节不稳定和阻塞的运动范围有限。其罕见的发病率导致对发病机制知之甚少。局部形式的TGCT（LTGCT）可导致显著的发病率，干扰患者的日常活动，在具有挑战性的病例中降低患者的生活质量。本研究旨在研究PPARγ（过氧化物酶体增殖物激活受体γ）和P53在LTGCT中的免疫组化表达，以更好地了解该病并提供潜在的治疗靶点。
方法：这项研究是横断面的，其中从病理学部门收集了27例LTGCT病例，医学院,开罗大学,开罗,埃及。纳入了2018年1月至2022年12月期间检索到的单发和多例LTGCT病例。并用抗PPARγ和P53抗体进行免疫组织化学染色。如果TGCT样本不足以切片，则将其排除在外，processing,和解释，过度固定，有过程工件，或为弥漫性TGCT型。染色表达的评分由ImageJ(美国国立卫生研究院，贝塞斯达,MD）使用阈值方法进行分析，并以面积百分比/高功率场表示。分析临床病理相关性。
结果：收集的27例LTGCT病例均位于患者的手部小关节。单发LGTCTs的病例占55.6%（n=15），而44.4%(n=12)的患者有多个与一个受影响的部位/病例相关的LTGCT(例如，一个手指中的多个肿瘤）。PPARγ在单核和多核肿瘤细胞和泡沫组织细胞的细胞质中表达，而P53表达主要在单核细胞核中。PPARγ与P53表达显著相关(r=0.9,P=0.000)。PPARγ(r=0.4,P=0.02)和P53(r=0.5,P=0.01)与肿瘤大小呈正相关。仅P53表达与肿瘤多重性呈正相关(r=0.4,P=0.03)。使用接收器工作特性曲线测试，检测TGCT多重性的P53截止分数≥20.5%，具有75%的灵敏度和80%的特异性。
结论：PPARγ和P53在LTGCT生长中具有重要作用，而P53在肿瘤多重性中起作用。它们可能是不适合切除的LTGCT的可能靶标。
方法：这项研究是横断面的，其中从病理学部门收集了27例LTGCT病例，医学院,开罗大学,开罗,埃及。纳入了2018年1月至2022年12月期间检索到的单发和多例LTGCT病例。并用抗PPARγ和P53抗体进行免疫组织化学染色。如果TGCT样本不足以切片，则将其排除在外，processing,和解释，过度固定，有过程工件，或为弥漫性TGCT型。染色表达的评分由ImageJ(美国国立卫生研究院，贝塞斯达,MD）使用阈值方法进行分析，并以面积百分比/高功率场表示。分析临床病理相关性。
结果：收集的27例LTGCT病例均位于患者的手部小关节。单发LGTCTs的病例占55.6%（n=15），而44.4%(n=12)的患者有多个与一个受影响的部位/病例相关的LTGCT(例如，一个手指中的多个肿瘤）。PPARγ在单核和多核肿瘤细胞和泡沫组织细胞的细胞质中表达，而P53表达主要在单核细胞核中。PPARγ与P53表达显著相关(r=0.9,P=0.000)。PPARγ(r=0.4,P=0.02)和P53(r=0.5,P=0.01)与肿瘤大小呈正相关。仅P53表达与肿瘤多重性呈正相关(r=0.4,P=0.03)。使用接收器工作特性曲线测试，检测TGCT多重性的P53截止分数≥20.5%，具有75%的灵敏度和80%的特异性。
结论：PPARγ和P53在LTGCT生长中具有重要作用，而P53在肿瘤多重性中起作用。它们可能是不适合切除的LTGCT的可能靶标。
