Transforming growth factor-beta 1: comparative immunohistochemical localization in human primary and metastatic...

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.