Williams M E, Nichols G E, Swerdlow S H, Stoler M H
Department of Pathology, University of Virginia School of Medicine, Charlottesville, USA.
Ann Oncol. 1995 Mar;6(3):297-9. doi: 10.1093/oxfordjournals.annonc.a059161.
Centrocytic/mantle cell lymphoma (MCL) is characterized by a specific chromosomal translocation, t(11;14)(q13;q32), which leads to deregulated expression of the G1 cyclin, cyclin D1 (PRAD1, CCND1, BCL1). Cyclin D1 overexpression has been demonstrated in MCL at the mRNA level by Northern blotting and at the protein level by both Western blotting and immunoperoxidase staining.
To assess the utility of in situ hybridization (ISH) to detect cyclin D1 mRNA expression in formalin-fixed, paraffin embedded tissue, five MCL specimens from three patients and two cases of B-cell small lymphocytic lymphoma (B-SLL) were studied. BCL1 major translocation cluster gene rearrangements had been previously documented in two MCL patients; the other MCL and the two B-SLL, showed no detectable BCL1 or cyclin D1 rearrangements.
ISH was performed using anti-sense 3H-labeled RNA probes for the cyclin D1 3' untranslated region (pPL7) and partial cyclin D1 cDNA (pPL8). ISH experiments using an anti-sense actin RNA probe demonstrated adequate RNA preservation in all cases. Each of five specimens of MCL demonstrated increased cyclin D1 mRNA. In contrast, neither of the two cases of B-SLL demonstrated detectable levels.
Overexpression of cyclin D1 mRNA can be detected in MCL by ISH using formalin fixed paraffin embedded tissue. The ISH technique may be useful in diagnosing and classifying low-grade B-cell lymphomas and should be applicable to the study of cyclin D1 mRNA expression in a broad spectrum of lymphoid proliferations and solid tumors.
中心细胞性/套细胞淋巴瘤（MCL）的特征是特定的染色体易位，即t(11;14)(q13;q32)，这导致G1期细胞周期蛋白细胞周期蛋白D1（PRAD1、CCND1、BCL1）的表达失调。通过Northern印迹法已在mRNA水平上证实MCL中存在细胞周期蛋白D1过表达，通过蛋白质印迹法和免疫过氧化物酶染色在蛋白质水平上也得到了证实。
为了评估原位杂交（ISH）检测福尔马林固定、石蜡包埋组织中细胞周期蛋白D1 mRNA表达的实用性，研究了来自3例患者的5个MCL标本和2例B细胞小淋巴细胞淋巴瘤（B-SLL）。先前已记录了2例MCL患者中的BCL1主要易位簇基因重排；其他MCL和2例B-SLL未检测到BCL1或细胞周期蛋白D1重排。
使用针对细胞周期蛋白D1 3'非翻译区（pPL7）和部分细胞周期蛋白D1 cDNA（pPL8）的反义3H标记RNA探针进行ISH。使用反义肌动蛋白RNA探针的ISH实验表明所有病例中RNA保存良好。5个MCL标本中的每一个都显示细胞周期蛋白D1 mRNA增加。相比之下，2例B-SLL均未检测到可检测水平。
使用福尔马林固定石蜡包埋组织通过ISH可在MCL中检测到细胞周期蛋白D1 mRNA的过表达。ISH技术可能有助于诊断和分类低度B细胞淋巴瘤，并且应该适用于研究广泛的淋巴增殖性疾病和实体瘤中细胞周期蛋白D1 mRNA的表达。
