Coco Dominique P, Hirsch Michelle S, Hornick Jason L
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Am J Surg Pathol. 2009 Dec;33(12):1795-801. doi: 10.1097/pas.0b013e3181b76477.
Smoothelin is a smooth muscle-specific cytoskeletal protein exclusively found in differentiated smooth muscle cells. This contrasts with other smooth muscle proteins (eg, h-caldesmon, alpha-smooth muscle actin, desmin, smooth muscle myosin), which are expressed in proliferative (early) stages of smooth muscle development and occasionally in other cell types (striated muscle, myofibroblasts, myoepithelial cells, pericytes). Smoothelin has been shown to be expressed predominantly in visceral smooth muscle and to a lesser extent in vascular smooth muscle. Smoothelin expression in mesenchymal tumors of the gastrointestinal (GI) tract has not been evaluated earlier. The purpose of this study was to determine whether immunostaining for smoothelin could help distinguish smooth muscle neoplasms from their morphologic mimics, particularly KIT-negative gastrointestinal stromal tumors (GISTs), desmin-positive GISTs, and desmoid fibromatosis. A total of 150 mesenchymal neoplasms of the GI tract, abdominal cavity, and retroperitoneum were retrieved from consult and surgical pathology archives, including 54 GISTs (8 KIT-negative; 13 desmin-positive), 17 GI leiomyosarcomas (LMS), 11 GI mural leiomyomas, 13 leiomyomas of the muscularis mucosae, 12 gastric schwannomas, 15 inflammatory myofibroblastic tumors, 9 cases of mesenteric desmoid fibromatosis, 10 dedifferentiated liposarcomas, and 9 malignant peripheral nerve sheath tumors. Immunostaining for smoothelin was performed on all cases. Cytoplasmic and nuclear staining was recorded. Cytoplasmic expression of smoothelin was present in all 24 (100%) benign smooth muscle tumors (mural leiomyomas and leiomyomas of the muscularis mucosae). In contrast, only 4 (24%) GI LMS showed cytoplasmic staining for smoothelin. None of the GISTs, desmoid tumors, inflammatory myofibroblastic tumors, schwannomas, dedifferentiated liposarcomas, or malignant peripheral nerve sheath tumors showed cytoplasmic reactivity for smoothelin. Interestingly, 7 (41%) GI LMS and 12 (22%) GISTs (all except 2 with an epithelioid component) showed multifocal, exclusively nuclear staining for smoothelin. Nuclear expression of smoothelin was not detected in any of the other tumor types examined. In summary, diffuse cytoplasmic staining for smoothelin is highly sensitive and specific for benign leiomyomas of the GI tract. Aberrant nuclear expression is common in GI LMS and may also be seen in GISTs, especially epithelioid and mixed-type tumors. These findings suggest that the extent and pattern of smoothelin expression may help differentiate between benign and malignant mesenchymal tumors of the GI tract, and may be useful in distinguishing leiomyomas from KIT-negative and/or desmin-positive GISTs.
平滑肌肌动蛋白是一种平滑肌特异性细胞骨架蛋白，仅在分化的平滑肌细胞中发现。这与其他平滑肌蛋白（如h-钙调蛋白、α-平滑肌肌动蛋白、结蛋白、平滑肌肌球蛋白）形成对比，后者在平滑肌发育的增殖（早期）阶段表达，偶尔也在其他细胞类型（横纹肌、肌成纤维细胞、肌上皮细胞、周细胞）中表达。已证明平滑肌肌动蛋白主要在内脏平滑肌中表达，在血管平滑肌中的表达程度较低。此前尚未评估胃肠道（GI）间叶肿瘤中平滑肌肌动蛋白的表达情况。本研究的目的是确定平滑肌肌动蛋白免疫染色是否有助于将平滑肌肿瘤与其形态学相似物区分开来，特别是KIT阴性胃肠道间质瘤（GISTs）、结蛋白阳性GISTs和韧带样纤维瘤病。从会诊和手术病理档案中检索了总共150例胃肠道、腹腔和腹膜后的间叶肿瘤，包括54例GISTs（8例KIT阴性；13例结蛋白阳性）、17例胃肠道平滑肌肉瘤（LMS）、11例胃肠道壁平滑肌瘤、13例黏膜肌层平滑肌瘤、12例胃神经鞘瘤、15例炎性肌成纤维细胞瘤、9例肠系膜韧带样纤维瘤病、10例去分化脂肪肉瘤和9例恶性外周神经鞘瘤。对所有病例进行了平滑肌肌动蛋白免疫染色。记录细胞质和细胞核染色情况。所有24例（100%）良性平滑肌肿瘤（壁平滑肌瘤和黏膜肌层平滑肌瘤）均有平滑肌肌动蛋白的细胞质表达。相比之下，只有4例（24%）胃肠道LMS显示平滑肌肌动蛋白的细胞质染色。GISTs、韧带样肿瘤、炎性肌成纤维细胞瘤、神经鞘瘤、去分化脂肪肉瘤或恶性外周神经鞘瘤均未显示平滑肌肌动蛋白的细胞质反应性。有趣的是，7例（41%）胃肠道LMS和12例（22%）GISTs（除含上皮样成分的2例之外的所有病例）显示平滑肌肌动蛋白多灶性、仅细胞核染色。在所检查的任何其他肿瘤类型中均未检测到平滑肌肌动蛋白的细胞核表达。总之，平滑肌肌动蛋白的弥漫性细胞质染色对胃肠道良性平滑肌瘤具有高度敏感性和特异性。异常的细胞核表达在胃肠道LMS中常见，在GISTs中也可见到，尤其是上皮样和混合型肿瘤。这些发现表明，平滑肌肌动蛋白表达的程度和模式可能有助于区分胃肠道良性和恶性间叶肿瘤，并且可能有助于将平滑肌瘤与KIT阴性和/或结蛋白阳性GISTs区分开来。
