Ladanyi Marc, Antonescu Cristina R, Drobnjak Marija, Baren Ann, Lui Man Yee, Golde David W, Cordon-Cardo Carlos
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Am J Pathol. 2002 Apr;160(4):1215-21. doi: 10.1016/S0002-9440(10)62548-5.
Alveolar soft part sarcoma (ASPS) is an unusual tumor of young adults with the characteristic presence on ultrastructural analysis of rhomboid or rectangular cytoplasmic crystals. These membrane-bound crystals are known to form within specific PAS-diastase-resistant electron-dense cytoplasmic granules. The composition of these crystals and the dense granules from which they are derived has remained elusive. After the detection of strong discrete granular cytoplasmic immunoreactivity in ASPS for monocarboxylate transporter 1 (MCT1) in the course of a broad immunohistochemical characterization of an MCT1 antibody, we studied the expression of MCT1 and its interacting partner, CD147, in a panel of 10 ASPS cases using appropriate antibodies. MCT1 is one of a family of widely expressed proton-linked transporters for monocarboxylates such as lactate and pyruvate. In all normal and neoplastic tissues studied to date, MCT1 immunoreactivity is limited to the cell surface. We find that the periodic acid-Schiff-diastase-resistant cytoplasmic granules of ASPS are strongly immunoreactive for MCT1 and CD147. Specifically, intense cytoplasmic granular positivity for MCT1 and CD147 was found in 7 of 10 and 8 of 10 ASPSs, respectively. Ultrastructural immunohistochemistry with immunogold labeling confirmed that the MCT1 immunoreactivity localized to the cytoplasmic electron-dense granules in ASPS. Western blot analysis of several ASPS cases confirmed that the protein reactive with the MCT1 antibody and that reactive with the CD147 antibody both migrated at the size expected for MCT1 and CD147, respectively. Thus, ASPS cells seem to accumulate MCT1-CD147 complexes in the specific cytoplasmic granules known to undergo crystallization. The possible basis for the overproduction or impaired surface localization of these proteins in ASPS remains unclear.
肺泡软组织肉瘤（ASPS）是一种好发于年轻人的罕见肿瘤，其特征在于超微结构分析显示存在菱形或矩形的胞质晶体。已知这些膜结合晶体在特定的耐PAS淀粉酶的电子致密胞质颗粒内形成。这些晶体及其来源的致密颗粒的组成一直不明确。在对一种单羧酸转运蛋白1（MCT1）抗体进行广泛的免疫组织化学特征分析过程中，检测到ASPS中MCT1存在强烈的离散颗粒状胞质免疫反应性后，我们使用合适的抗体研究了10例ASPS病例中MCT1及其相互作用伴侣CD147的表达。MCT1是广泛表达的质子偶联单羧酸转运蛋白家族的一员，可转运乳酸和丙酮酸等单羧酸。在迄今为止研究的所有正常和肿瘤组织中，MCT1免疫反应性仅限于细胞表面。我们发现，ASPS的耐高碘酸-希夫淀粉酶的胞质颗粒对MCT1和CD147有强烈的免疫反应性。具体而言，在10例ASPS中，分别有7例和8例对MCT1和CD147呈现强烈的胞质颗粒阳性。免疫金标记的超微结构免疫组织化学证实，ASPS中MCT1免疫反应性定位于胞质电子致密颗粒。对几例ASPS病例的蛋白质印迹分析证实，与MCT1抗体反应的蛋白和与CD147抗体反应的蛋白分别在MCT1和CD147预期的大小处迁移。因此，ASPS细胞似乎在已知会发生结晶的特定胞质颗粒中积累MCT1-CD147复合物。这些蛋白质在ASPS中过度产生或表面定位受损的可能原因仍不清楚。
