Proliferation and hypoxia in human squamous cell carcinoma of the cervix: First report of combined immunohistochemical assays
Proliferation and hypoxia in human squamous cell carcinoma of the cervix: First report of combined immunohistochemical assays
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DOI：
10.1016/s0360-3016(96)00539-1
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发表时间：
1997-03-01
影响因子：
7
通讯作者：
Varia, MA
中科院分区：
文献类型：
--
作者：
Kennedy, AS;Raleigh, JA;Varia, MA
目的：在开始治疗前通过免疫组织化学方法表征人宫颈鳞状细胞癌缺氧和增殖的分布，方法和材料：原发性宫颈鳞状细胞癌患者接受单次输注 2-硝基咪唑、哌莫硝唑（0.5 g/m(2) 静脉注射），并在 24 小时后进行穿刺活检。 取原发肿瘤，将组织用福尔马林固定，石蜡包埋，切片用于免疫组织化学。通过单克隆抗体与恶性细胞中还原激活的哌莫硝唑加合物结合来检测缺氧，通过市售单克隆抗体在肿瘤细胞中检测内源性 MIB-1 和 PCNA 染色，使用点计数来定量肿瘤细胞免疫染色的 MIB-1、PCNA 和缺氧标记物结合的分数。 哌莫硝唑结合远离血管，坏死区域没有染色，只有极少的非特异性染色，主要在角蛋白中，一般来说，MIB-1和PCNA的细胞免疫染色没有对哌莫硝唑结合进行免疫染色，MIB-1和PCNA的细胞免疫染色没有显示出明显的地理偏好，例如接近脉管系统，定量 比较显示缺氧标志物结合与增殖之间存在反比关系，结论：哌莫硝唑结合的免疫组织化学染色与人类肿瘤中缺氧细胞的存在一致，可能有助于在放射治疗前估计肿瘤缺氧情况，哌莫硝唑结合的免疫染色是内源性增殖标志物免疫组织化学测定的理想补充，可以 肿瘤缺氧与其他生理参数的比较，这些参数可用于选择接受专门设计的放射方案的患者，以抵消缺氧和/或增殖对治疗的负面影响，哌莫硝唑结合和增殖标记物之间的负相关是需要验证的初步结果，(C) 1997 Elsevier Science Inc.
Purpose: To characterize the distribution of hypoxia and proliferation in human squamous cell carcinoma of the cervix via an immunohistochemical approach prior to initiation of therapy,Methods and Materials: Patients with primary squamous cell carcinoma of the cervix uteri received a single infusion of the 2-nitroimidazole, pimonidazole (0.5 g/m(2) i.v.), and 24 h later punch biopsies of the primary tumor were taken, Tissue was formalin fixed, paraffin embedded, and sectioned for immunohistochemistry. Hypoxia was detected by monoclonal antibody binding to adducts of reductively activated pimonidazole in malignant cells, Staining for endogenous MIB-1 and PCNA was detected in tumor cells via commercially available monoclonal antibodies, Point counting was used to quantitate the fraction of tumor cells immunostained for MIB-1, PCNA, and hypoxia marker binding,Results: Immunostaining for pimonidazole binding was distant from blood vessels, There was no staining in necrotic regions, and only minimal nonspecific staining, mostly in keratin, In general, cells immunostaining for MIB-1 and PCNA did not immunostain for pimonidazole binding, Cells immunostaining for MIB-1 and PCNA showed no obvious geographic predilection such as proximity to vasculature, Quantitative comparison showed an inverse relationship between hypoxia marker binding and proliferation,Conclusions: Immunohistochemical staining for pimonidazole binding is consistent with the presence of hypoxic cells in human tumors and may be useful for estimating tumor hypoxia prior to radiation therapy, Immunostaining for pimonidazole binding is an ideal complement to immunohistochemical assays for endogenous proliferation markers allowing for comparisons of tumor hypoxia with other physiological parameters, These parameters might be used to select patients for radiation protocols specifically designed to offset the negative impact of hypoxia and/or proliferation on therapy, The inverse relationship between pimonidazole binding and proliferation markers is a preliminary result requiring verification, (C) 1997 Elsevier Science Inc.