Nafe Reinhold, Franz Kea, Schlote Wolfgang, Schneider Berthold
Department of Neuroradiology, Clinics of Johann Wolfgang Goethe-University, D-60528 Frankfurt, Germany.
Oncol Rep. 2006 Sep;16(3):555-62.
A deeper knowledge about histopathological criteria with a significant impact on the prognosis of patients with glioblastomas is worthwhile, since these patients may show a considerable difference in the time of survival. Investigation of the morphology of perinecrotic tumor cell nuclei is a promising approach, because the expression of specific molecules in these cells has been associated with a more aggressive behaviour of the tumors. In our series of patients with documented clinical course, 11 patients had a survival of at least 24 months and we compared this group with a group of 10 patients with maximum survival of 12 months. Digital microscopic image analysis was performed in paraffin sections from the primary surgical specimen. Three hundred perinecrotic tumor cell nuclei per case and 300 nuclei per case from tumor cells lying more distant from the tumor necroses ('distant zone' nuclei) were measured. The ratio for the numerical nuclear density between both types of nuclei was significantly larger in cases with short survival indicating a more pronounced nuclear density of perinecrotic nuclei in relation to the 'distant zone' nuclei in these tumors. In cases with long survival, on the contrary, perinecrotic tumor cells exhibited an only slightly larger numerical density compared with 'distant zone' nuclei. Mean values and standard deviations from parameters of nuclear shape (Fourier-amplitudes) had significantly smaller values in short-time survivors indicating a tendency towards a more circular nuclear shape with less pronounced intratumoral variation in that group. Based on the morphometric results, all cases could be correctly reclassified as short- or long-time survivors by means of cross-validated discriminant analysis. In conclusion, the results confirm significant morphological differences between tumors from patients with short and with long survival regarding morphology of both types of tumor cell nuclei. It seems likely, that histomorphometry of tumor cell nuclei could be a promising approach for the assessment of the individual prognosis of patients with glioblastomas.
深入了解对胶质母细胞瘤患者预后有重大影响的组织病理学标准是很有价值的,因为这些患者在生存时间上可能存在相当大的差异。研究坏死周围肿瘤细胞核的形态是一种有前景的方法,因为这些细胞中特定分子的表达与肿瘤更具侵袭性的行为有关。在我们有记录临床病程的患者系列中,11例患者存活至少24个月,我们将该组与10例最大存活12个月的患者组进行了比较。对原发手术标本的石蜡切片进行了数字显微图像分析。每例测量300个坏死周围肿瘤细胞核以及300个距离肿瘤坏死较远的肿瘤细胞的核(“远区”核)。短生存期病例中,两种类型细胞核的数字核密度比值显著更高,表明这些肿瘤中坏死周围核的核密度相对于“远区”核更为明显。相反,在长生存期病例中,坏死周围肿瘤细胞与“远区”核相比,数字密度仅略高。核形状参数(傅里叶振幅)的平均值和标准差在短生存期患者中显著较小,表明该组有核形状更趋于圆形且肿瘤内变异不太明显的趋势。基于形态计量学结果,通过交叉验证判别分析,所有病例均可正确重新分类为短生存期或长生存期患者。总之,结果证实了短生存期和长生存期患者的肿瘤在两种类型肿瘤细胞核形态方面存在显著的形态学差异。肿瘤细胞核的组织形态计量学似乎可能是评估胶质母细胞瘤患者个体预后的一种有前景的方法。