Eastham J A, Truong L D, Rogers E, Kattan M, Flanders K C, Scardino P T, Thompson T C
Matsunaga-Conte Prostate Cancer Research Center, Houston, Texas.
Lab Invest. 1995 Nov;73(5):628-35.
We have shown previously that primary prostate cancer demonstrates significant extracellular accumulation of transforming growth factor-beta 1 (TGF-beta 1). To further investigate the potential role of TGF-beta 1 in prostate cancer progression, we evaluated an expanded series of primary prostatic carcinomas and associated lymph node metastases.
Prostate tissue samples from 37 patients were examined. Three were organ donors, all less than 30 years of age, whose prostates were included as normal controls. Eighteen had undergone radical prostatectomy and pelvic lymph node dissection. Eleven were without evidence of metastasis, whereas seven were found to have prostate cancer within at least one of their pelvic lymph nodes. Sixteen had undergone transurethral resection of the prostate for benign disease, yet all had prostate cancer within the resected specimen (15 were stage T1b; 1 was stage T1a). Twelve of the patients with stage T1b disease underwent pelvic lymph node dissection and implantation of radioactive gold seeds. All 12 had prostate cancer in at least one lymph node. All specimens were examined for the level of expression and localization of TGF-beta 1 by immunohistochemistry using Ab that distinguish intracellular from extracellular TGF-beta 1.
Normal prostate tissue and benign prostatic hyperplasia demonstrated negative or weak intracellular and extracellular staining for TGF-beta 1. By comparison, 29 of 34 primary prostate cancers showed extensive extracellular TGF-beta 1 staining with pronounced intracellular accumulation within epithelial cells in 13 of 34 patients. There was no difference in the staining pattern for extracellular TGF-beta 1 between primary cancers with and without pelvic lymph node metastases. However, in primary cancers without pelvic lymph node metastases, only 1 of 15 patients showed strong intracellular staining for TGF-beta 1 compared with 12 of 19 primary tumors with metastatic disease. In addition, only 2 of 19 lymph node metastases demonstrated weak extracellular TGF-beta 1 staining, but all 19 contained intracellular TGF-beta 1.
These findings confirm our previous observation that prostate cancer exhibits enhanced intracellular and extracellular accumulation of TGF-beta 1 relative to normal prostate tissue and benign prostatic hyperplasia. In addition, our study documented a significantly more pronounced accumulation of intracellular TGF-beta 1 in primary prostate cancer with metastasis than in primary tumors without metastasis. Moreover, although the pattern of intracellular TGF-beta 1 staining observed in the primary tumor is maintained in the metastasis, a lack of extracellular accumulation of TGF-beta 1 in the metastatic site was noted. This differential pattern may be biologically important and could conceivably reflect a role for TGF-beta 1 in disease progression.
我们之前已经表明，原发性前列腺癌表现出转化生长因子-β1（TGF-β1）在细胞外的显著蓄积。为了进一步研究TGF-β1在前列腺癌进展中的潜在作用，我们评估了一系列扩展的原发性前列腺癌及相关淋巴结转移灶。
检查了37例患者的前列腺组织样本。其中3例是器官捐献者，年龄均小于30岁，其前列腺作为正常对照。18例患者接受了前列腺根治术和盆腔淋巴结清扫术。11例无转移证据，而7例在至少一个盆腔淋巴结中发现有前列腺癌。16例因良性疾病接受了经尿道前列腺切除术，但所有切除标本中均有前列腺癌（15例为T1b期；1例为T1a期）。12例T1b期疾病患者接受了盆腔淋巴结清扫并植入放射性金种子。所有12例患者至少有一个淋巴结存在前列腺癌。使用能区分细胞内和细胞外TGF-β1的抗体，通过免疫组织化学检查所有标本中TGF-β1的表达水平和定位。
正常前列腺组织和良性前列腺增生对TGF-β1表现为细胞内和细胞外染色阴性或弱阳性。相比之下，34例原发性前列腺癌中有29例显示细胞外TGF-β1广泛染色，34例患者中有13例上皮细胞内有明显的细胞内蓄积。有盆腔淋巴结转移和无盆腔淋巴结转移的原发性癌在细胞外TGF-β1染色模式上没有差异。然而，在无盆腔淋巴结转移的原发性癌中，15例患者中只有1例显示TGF-β1细胞内强染色，而在有转移疾病的19例原发性肿瘤中有12例如此。此外，19个淋巴结转移灶中只有2个显示细胞外TGF-β1弱阳性染色，但所有19个均含有细胞内TGF-β1。
这些发现证实了我们之前的观察，即相对于正常前列腺组织和良性前列腺增生，前列腺癌表现出TGF-β1细胞内和细胞外蓄积增强。此外，我们的研究记录了有转移的原发性前列腺癌中细胞内TGF-β1的蓄积比无转移的原发性肿瘤明显更显著。而且，尽管在转移灶中观察到原发性肿瘤中细胞内TGF-β1的染色模式得以维持，但在转移部位未发现TGF-β1的细胞外蓄积。这种差异模式可能具有生物学重要性，并且可以想象反映了TGF-β1在疾病进展中的作用。
