Jha Prerana, Agarwal Shipra, Pathak Pankaj, Srivastava Arti, Suri Vaishali, Sharma Mehar Chand, Chosdol Kunzang, Srivastava Tapasya, Gupta Deepak, Gupta Aditya, Suri Ashish, Sarkar Chitra
Department of Pathology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India.
Cancer Genet Cytogenet. 2010 Apr 15;198(2):126-34. doi: 10.1016/j.cancergencyto.2009.12.018.
There are few reports of loss of heterozygosity (LOH) of 1p and 19q in astrocytic tumors, especially glioblastoma multiforme (GBM). We evaluated 1p and 19q (either or both) heterozygosity status in 71 astrocytomas, including 6 pediatric cases: 20 diffuse astrocytomas (DA), 9 anaplastic astrocytomas (AA), and 42 GBM. In the GBMs, p53 protein expression was assessed by immunohistochemistry and epidermal growth factor receptor (EGFR) gene amplification by fluorescence in situ hybridization; TP53 sequencing was done in 15 of the GBMs. In adults, LOH of 1p or 19q was detected in 16% of DAs and 50% of GBMs; none of the AAs showed this alteration. In GBMs, LOH of 19q was most common (26%), followed by combined 1p and 19q LOH (13%) and 1p LOH (10%). Pediatric GBMs also harbored isolated 1p and 19q LOH (50%). Notably, LOH of 1p or 19q LOH was more frequent in p53 immunopositive secondary GBMs (61%) than in primary GBMs (17%). This suggests that LOH of 1p and 19q may be acquired during progression to secondary GBMs. Thus, 1p and 19q LOH can occur in astrocytic tumors, most commonly in secondary GBMs without morphological correlation with an oligodendroglial histology. The clinical significance of recognition of this subset of GBMs is based on several recent reports of association with better prognosis, although long-term follow-up studies are required.
关于星形细胞瘤,尤其是多形性胶质母细胞瘤(GBM)中1p和19q杂合性缺失(LOH)的报道较少。我们评估了71例星形细胞瘤中1p和19q(任一或两者)的杂合性状态,其中包括6例儿科病例:20例弥漫性星形细胞瘤(DA)、9例间变性星形细胞瘤(AA)和42例GBM。在GBM中,通过免疫组织化学评估p53蛋白表达,通过荧光原位杂交评估表皮生长因子受体(EGFR)基因扩增;对15例GBM进行了TP53测序。在成人中,1p或19q的LOH在16%的DA和50%的GBM中被检测到;所有AA均未显示这种改变。在GBM中,19q的LOH最常见(26%),其次是1p和19q联合LOH(13%)和1p LOH(10%)。儿科GBM也存在孤立的1p和19q LOH(50%)。值得注意的是,p53免疫阳性的继发性GBM中1p或19q LOH比原发性GBM更常见(61%对17%)。这表明1p和19q的LOH可能在向继发性GBM进展过程中获得。因此,1p和19q LOH可发生在星形细胞瘤中,最常见于继发性GBM,且与少突胶质细胞组织学无形态学相关性。尽管需要长期随访研究,但最近有几份报告表明识别这一GBM亚组具有更好的预后,这体现了其临床意义。