Portela-Gomes Guida Maria, Grimelius Lars, Stridsberg Mats, Bresaola Enrica, Viale Giuseppe, Pelosi Giuseppe
Unit of Pathology, Department of Genetics and Pathology, University Hospital, 751 85 Uppsala, Sweden.
Virchows Arch. 2005 Jun;446(6):604-12. doi: 10.1007/s00428-005-1222-6. Epub 2005 May 20.
Chromogranin A (CgA) and its valuable complement synaptic vesicle protein 2 (SV2) are neuroendocrine (NE) markers. Post-translational processing of CgA has been reported to vary in different NE cell types and tumors, but little is known regarding the expression of various CgA epitopes and SV2 in NE pulmonary tumors. We studied the immunoreactivity to six CgA epitopes and SV2 in ten typical (TC) and ten atypical (ACT) carcinoids, five large-cell NE carcinomas (LCNEC) and five small-cell carcinomas (SCLC), also comparing the results with clinicopathological characteristics of tumors. The sequences CgA 17--38 (vasostatin), 176--195 (chromacin), 375--384 (parastatin) and 411--424 (C-terminal parastatin) and SV2 were relevant markers for the CT/ATC group, whereas the antibody to CgA 176--195 was a better marker for the LCNEC/SCLC group. An inverse correlation was found between proliferative activity and granule-related markers in the CT/ACT group, and a direct correlation in poorly differentiated tumors. The expression of granule-related markers did not correlate with hormone content or clinical characteristics of NE tumors. The expression of CgA epitopes and SV2 occurs in all NE tumors, differing between better differentiated and poorly differentiated tumors but not within the respective groups.
嗜铬粒蛋白A(CgA)及其重要的补充物突触小泡蛋白2(SV2)是神经内分泌(NE)标志物。据报道,CgA的翻译后加工在不同的NE细胞类型和肿瘤中有所不同,但关于各种CgA表位和SV2在NE肺肿瘤中的表达情况知之甚少。我们研究了10例典型类癌(TC)、10例非典型类癌(ACT)、5例大细胞神经内分泌癌(LCNEC)和5例小细胞癌(SCLC)对6种CgA表位和SV2的免疫反应性,并将结果与肿瘤的临床病理特征进行比较。CgA 17 - 38(血管抑素)、176 - 195(嗜铬粒素)、375 - 384(副抑素)和411 - 424(C末端副抑素)序列以及SV2是CT/ATC组的相关标志物,而针对CgA 176 - 195的抗体是LCNEC/SCLC组更好的标志物。在CT/ACT组中,增殖活性与颗粒相关标志物呈负相关,在低分化肿瘤中呈正相关。颗粒相关标志物的表达与NE肿瘤的激素含量或临床特征无关。CgA表位和SV2的表达存在于所有NE肿瘤中,在高分化和低分化肿瘤之间存在差异,但在各自组内无差异。