Krajewska M, Krajewski S, Epstein J I, Shabaik A, Sauvageot J, Song K, Kitada S, Reed J C
Burnham Institute, La Jolla, California 92037, USA.
Am J Pathol. 1996 May;148(5):1567-76.
Proteins encoded by bcl-2 family genes are important regulators of programmed cell death and apoptosis. Alterations in the expression of these apoptosis-regulating genes can contribute to the origins of cancer, as well as adversely influence tumor responses to chemo- and radiotherapy. Using antibodies specific for the Bcl-2, Bax, Bcl-X, and Mcl-1 proteins in combination with immunohistochemical methods, we examined for the first time the expression of these bcl-2 family genes in 64 cases of adenocarcinoma of the prostate, including 10 Gleason grade 2 to 4 tumors, 21 grade 5 to 7 tumors, 17 grade 8 to 10 tumors, 8 lymph node metastases, and 8 bone metastases. In addition, 24 cases of prostatic intraepithelial neoplasia (PIN) or PIN coexisting with carcinoma were also evaluated. All immunostaining results were scored with regard to approximate percentage of positive tumor cells and relative immunostaining intensity. Expression of the anti-apoptotic protein Bcl-2 was present in 16 of 64 (25%) adenocarcinomas and tended to be more frequent in high grade tumors (Gleason grade 8 to 10; 41%) and nodal metastases (38%) than in lower grade (Gleason 2 to 7) primary tumors (16%; P < 0.05). Bcl-X was expressed in all 64 (100%) tumors evaluated. Bcl-X immunointensity was generally stronger in high grade primary tumors (grade 8 to 10) and metastases compared with PIN and low grade neoplasms (P < 0.0001). In addition, the proportion of specimens with > 50% Bcl-X-immunopositive tumor cells also was higher in advanced grade primary tumors (Gleason 8 to 10) and metastases than in PIN and low grade tumors (Gleason 2 to 7; P < 0.005). The anti-apoptotic protein Mcl-1 was expressed in 52 of 64 (81%) tumors, compared with only 9 of 24 (38%) cases of PIN (P < 0.001). In addition, the percentage of Mcl-1-positive cells was typically higher in Gleason grade 8 to 10 tumors and metastases than in PIN or lower grade tumors (P = 0.025). In contrast, the pro-apoptotic protein Bax was expressed in all prostate cancers evaluated, with high percentages of immunopositive cells and strong immunointensity typically occurring regardless of tumor grade. The findings suggest that expression of several anti-apoptotic members of the bcl-2 gene family, including bcl-2, bcl-X, and mcl-1 increases during progression of prostate cancers, a finding that may be relevant to the hormone-insensitive, metastatic phenotype of most advanced adenocarcinomas of the prostate.
bcl-2家族基因编码的蛋白质是程序性细胞死亡和凋亡的重要调节因子。这些凋亡调节基因表达的改变可导致癌症的发生，并对肿瘤对化疗和放疗的反应产生不利影响。我们使用针对Bcl-2、Bax、Bcl-X和Mcl-1蛋白的特异性抗体，结合免疫组织化学方法，首次检测了64例前列腺腺癌中这些bcl-2家族基因的表达情况，其中包括10例Gleason 2至4级肿瘤、21例5至7级肿瘤、17例8至10级肿瘤、8例淋巴结转移瘤和8例骨转移瘤。此外，还评估了24例前列腺上皮内瘤变（PIN）或与癌共存的PIN。所有免疫染色结果均根据阳性肿瘤细胞的大致百分比和相对免疫染色强度进行评分。抗凋亡蛋白Bcl-2在64例（25%）腺癌中有16例表达，在高级别肿瘤（Gleason 8至10级；41%）和淋巴结转移瘤（38%）中比低级别（Gleason 2至7级）原发性肿瘤（16%）更常见（P<0.05）。Bcl-X在所有64例（1...展开全部译文bcl-2家族基因编码的蛋白质是程序性细胞死亡和凋亡的重要调节因子。这些凋亡调节基因表达的改变可导致癌症的发生，并对肿瘤对化疗和放疗的反应产生不利影响。我们使用针对Bcl-2、Bax、Bcl-X和Mcl-1蛋白的特异性抗体，结合免疫组织化学方法，首次检测了64例前列腺腺癌中这些bcl-2家族基因的表达情况，其中包括10例Gleason 2至4级肿瘤、21例5至7级肿瘤、17例8至10级肿瘤、8例淋巴结转移瘤和8例骨转移瘤。此外，还评估了24例前列腺上皮内瘤变（PIN）或与癌共存的PIN。所有免疫染色结果均根据阳性肿瘤细胞的大致百分比和相对免疫染色强度进行评分。抗凋亡蛋白Bcl-2在64例（25%）腺癌中有16例表达，在高级别肿瘤（Gleason 8至10级；41%）和淋巴结转移瘤（—38%）中比低级别（Gleason 2至7级）原发性肿瘤（16%）更常见（P<0.05）。Bcl-X在所有64例（100%）评估的肿瘤中均有表达。与PIN和低级别肿瘤相比，Bcl-X免疫强度在高级别原发性肿瘤（8至10级）和转移瘤中通常更强（P<0.0001）。此外，Bcl-X免疫阳性肿瘤细胞>50%的标本比例在高级别原发性肿瘤（Gleason 8至10级）和转移瘤中也高于PIN和低级别肿瘤（Gleason 2至7级；P<0.005）。抗凋亡蛋白Mcl-1在64例（81%）肿瘤中有52例表达，而在24例（38%）PIN病例中只有9例表达（P<0.001）。此外，Mcl-1阳性细胞的百分比在Gleason 8至10级肿瘤和转移瘤中通常高于PIN或低级别肿瘤（P=0.025）。相比之下，促凋亡蛋白Bax在所有评估的前列腺癌中均有表达，无论肿瘤级别如何，免疫阳性细胞百分比通常都很高，免疫强度也很强。这些发现表明，包括bcl-—2、bcl-X和mcl-1在内的bcl-2基因家族的几个抗凋亡成员的表达在前列腺癌进展过程中增加，这一发现可能与大多数晚期前列腺腺癌的激素不敏感、转移表型有关。
