Xu J L, Lai R, Kinoshita T, Nakashima N, Nagasaka T
Department of Laboratory Medicine, Nagoya University School of Medicine, Tsurumai-cho 65, Showa-ku, Japan.
J Clin Pathol. 2002 Jul;55(7):530-4. doi: 10.1136/jcp.55.7.530.
Abnormalities involving proliferation, apoptosis, and angiogenesis are important in tumorigenesis. The purpose of this study was to examine these three biological processes, and their relation with the clinical stage and cytological grade in multiple myeloma (MM).
Fifty four newly diagnosed patients with MM were studied by immunohistochemistry using bone marrow clot sections. Proliferation and apoptosis were evaluated for the proportion of MM cells (indicated by morphology and CD138 reactivity) positive for the Ki67 antigen and single stranded DNA (ssDNA), respectively. Angiogenesis was evaluated by measuring the intratumoral microvessel density (IMVD) and by assessing the immunoreactivity of vascular endothelial growth factor (VEGF).
There were 30 men and 24 women (median age, 65 years; range, 37-84). At initial presentation, 15 (28%) were in Durie stage I, 15 (28%) in stage II, and 24 (44%) in stage III. Advanced clinical stage correlated with high cytological grade (p < 0.03). The medians for Ki67, ssDNA, and IMVD were 4.4% (range, 0-15%), 0.2% (range, 0-2.8%), and 15.5 (range, 0-63), respectively. Among these three continuous parameters, the only significant correlation was that between Ki67 and IMVD (p < 0.0001). Both Ki67 and IMVD also correlated with the clinical stage, cytological grade, and VEGF positivity (p <0.05). No correlation was found between ssDNA and all of the other parameters.
These data suggest that proliferation is associated with angiogenesis in MM. Furthermore, proliferation and angiogenesis, but not apoptosis, may be important in disease progression. Lastly, increased production of VEGF may be one of the contributing factors to the increase in intratumoral vascularity seen in advanced MM.
涉及增殖、凋亡和血管生成的异常在肿瘤发生过程中具有重要意义。本研究的目的是检测这三个生物学过程，以及它们与多发性骨髓瘤（MM）临床分期和细胞学分级的关系。
采用骨髓凝块切片免疫组织化学方法对54例新诊断的MM患者进行研究。分别通过Ki67抗原和单链DNA（ssDNA）阳性的MM细胞比例（通过形态学和CD138反应性指示）评估增殖和凋亡。通过测量瘤内微血管密度（IMVD）和评估血管内皮生长因子（VEGF）的免疫反应性来评估血管生成。
患者中男性30例，女性24例（中位年龄65岁；范围37 - 84岁）。初诊时，15例（28%）处于Durie I期，15例（28%）处于II期，24例（44%）处于III期。晚期临床分期与高细胞学分级相关（p < 0.03）。Ki67、ssDNA和IMVD的中位数分别为4.4%（范围0 - 15%）、0.2%（范围0 - 2.8%）和15.5（范围0 - 63）。在这三个连续参数中，唯一显著的相关性是Ki67与IMVD之间的相关性（p < 0.0001）。Ki67和IMVD也均与临床分期、细胞学分级和VEGF阳性相关（p < 0.05）。未发现ssDNA与所有其他参数之间存在相关性。
这些数据表明，MM中的增殖与血管生成相关。此外，增殖和血管生成而非凋亡可能在疾病进展中起重要作用。最后，VEGF产生增加可能是晚期MM中瘤内血管增多的促成因素之一。
