Boruah Dibyajyoti, Deb Prabal, Srinivas V, Mani N S
Department of Pathology, Armed Forces Medical College, Pune 411040, Maharashtra, India.
Department of Pathology, Armed Forces Medical College, Pune 411040, Maharashtra, India.
Microvasc Res. 2014 May;93:52-61. doi: 10.1016/j.mvr.2014.03.002. Epub 2014 Mar 19.
Modifications of nuclear morphology in conjunction with alteration in microvascular configuration are essential features encountered during the progression of glial tumors. In order to gain more insight into tumor biology of gliomas, objectives of the study were selected (a) to correlate morphometrically evaluated nuclear parameters [nuclear area (NA), nuclear perimeter (NP), nuclear density (ND), percentage of total nuclear area (%TNA)] and microvessel parameters [microvessel density (MVD), microvessel caliber (VC), microvessel cross sectional area (VCSA), total microvessel boundary density (TVBD), percentage of total VCSA (%TVCSA)] with WHO grading; (b) extend such correlations to the ratio parameters: ratio of MVD to ND (MDV/ND), ratio of TVBD to %TNA (TVBD/%TNA) and ratio of %TVCSA to %TNA (%TVCSA/%TNA); and (c) to correlate microvessel and ratio parameters with NP and ND.
A total of thirty gliomas managed at this institute during 2009-2012 were evaluated for various nuclear and microvessel parameters by image morphometry using a computerized digital photomicrograph system. For assessment of microvessel parameters CD34-immunostained sections were used while nuclear morphometry was performed on routine hematoxylin-eosin-stained sections. Appropriate statistical analysis was performed in correlation studies.
All nuclear morphometric parameters showed strong positive correlation with tumor grades (r>0.7). In contrast, though all microvessel parameters exhibited positive correlation with grades, the parameters TVBD and %TVCSA showed strong positive correlation. The ratio parameters (MVD/ND) and (TVBD/%TNA) showed negative correlation with grades, whereas (%TVCSA/%TNA) did not exhibit meaningful correlation with grades. Further, while all microvessel parameters showed positive correlation with NP and ND; ratio parameters showed negative correlation with them.
This study indicates that the parameters related to tumor growth (NA, NP, ND, %TNA), and angiogenesis showed increasing trend with tumor grades simultaneously; whereas the parameters related to supply of nutrients per nucleus showed decreasing trends with tumor grades, nuclear size and nuclear density. Thus, the former accounts for increased cellularity, mitosis, and vascular proliferation, while the latter culminates in tumor necrosis, all of which are essential components for grading of gliomas. The present study will therefore have a vital role as surrogate markers of grading of tumor.
核形态的改变以及微血管结构的变化是胶质细胞瘤进展过程中的基本特征。为了更深入了解胶质瘤的肿瘤生物学特性，本研究的目的是：（a）将形态计量学评估的核参数[核面积（NA）、核周长（NP）、核密度（ND）、总核面积百分比（%TNA）]和微血管参数[微血管密度（MVD）、微血管管径（VC）、微血管横截面积（VCSA）、总微血管边界密度（TVBD）、总VCSA百分比（%TVCSA）]与世界卫生组织（WHO）分级相关联；（b）将这种关联扩展到比率参数：MVD与ND的比率（MDV/ND）、TVBD与%TNA的比率（TVBD/%TNA）以及%TVCSA与%TNA的比率（%TVCSA/%TNA）；（c）将微血管参数和比率参数与NP和ND相关联。
2009年至2012年在本研究所治疗的30例胶质瘤，使用计算机化数字显微图像系统通过图像形态计量学评估各种核参数和微血管参数。评估微血管参数时使用CD34免疫染色切片，而核形态计量学则在常规苏木精-伊红染色切片上进行。在相关性研究中进行了适当的统计分析。
所有核形态计量参数与肿瘤分级均呈强正相关（r>0.7）。相比之下，虽然所有微血管参数与分级均呈正相关，但TVBD和%TVCSA参数呈强正相关。比率参数（MVD/ND）和（TVBD/%TNA）与分级呈负相关，而（%TVCSA/%TNA）与分级无显著相关性。此外，虽然所有微血管参数与NP和ND呈正相关；但比率参数与它们呈负相关。
本研究表明，与肿瘤生长相关的参数（NA、NP、ND、%TNA）和血管生成与肿瘤分级同时呈增加趋势；而与每个细胞核营养供应相关的参数随肿瘤分级、核大小和核密度呈下降趋势。因此，前者导致细胞增多、有丝分裂和血管增殖增加，而后者最终导致肿瘤坏死，所有这些都是胶质瘤分级必不可少的组成部分。因此，本研究作为肿瘤分级的替代标志物将发挥重要作用。
