TNF/IL-1/NIK/NF-kappa B transduction pathway: a comparative study in normal and pathological human prostate (benign hyperplasia and carcinoma).

AIMS: Tumour necrosis factor (TNF)-alpha induces death or cell proliferation by activation of nuclear factor (NF)-kappaB, also activated by interleukin (IL)-1 alpha. The aim was to investigate upstream and downstream components of NIK transduction pathway in normal (NP), benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN) and prostatic carcinoma (PC). METHODS AND RESULTS: Immunohistochemistry and Western blotting were performed. In NP, the cytoplasm of epithelial cells was intensely immunoreactive to IL-1 receptor-associated kinase (IRAK), TNF receptor-associated factor (TRAF)-6, NF-kappaB inducing kinase (NIK), I kappa kappa alpha/beta, I kappaB alpha and p-I kappaB; weakly to NF-kappaB-p50; and negative to NF-kappaB-p65. BPH samples were intensely immunoreactive to IRAK, TRAF-6, NIK, I kappa kappa alpha/beta, I kappaB alpha, p-I kappaB; weakly to NF-kappaB-p50 and NF-kappaB-p65. Whereas low-grade PIN showed intermediate results between NP and BPH, results in high-grade PIN were similar to those found in PC (low Gleason). In PC, immunoreactivity was intense for IRAK, TRAF-6, NIK, I kappa kappa alpha/beta (increasing with Gleason), I kappaB alpha, p-I kappaB (decreasing with Gleason); weak for NF-kappaB-p50 and NF-kappaB-p65 (decreasing with Gleason). Nuclear NF-kappaB was observed in PC. CONCLUSIONS: NF-kappaB enhances cell proliferation, but also ATF-2 or Elk-1. Since IL-1 and TNF-alpha are related to inflammation and their immunoexpression increases in PC, inhibition of these cytokines might be a possible target for PC treatment, because they decrease the activity of all transduction pathway members that activate transcription factors such as NF-kappaB, Elk-1 or ATF-2.

[Prevalence of prostatic intraepithelial neoplasia in Spain]. / Prevalencia de la neoplasia intraepitelial prostática en España.

OBJECTIVE: To study the prevalence of high grade prostatic intraepithelial neoplasia in a Spanish population and to compare it with the prevalence in Caucasians of other countries and Afro-Americans. METHODS: 162 prostates obtained at autopsy from Spanish men aged 20-80 years, were fixed in 10% formalin and slices perpendicular to the posterior margin were made every 3-4 mm along its entire length. All blocks were embedded in paraffin and examined microscopically. Mapping of focality and site of the high grade prostatic intraepithelial neoplasia was done for each case. The Wayne University autopsy study was used for comparison of the prevalence in other countries and races. RESULTS: 146 prostates from men with a mean age of 48.5 years were considered valid for histological analysis. There were 42 high grade prostatic intraepithelial neoplasia; 20 were focal and 22 multifocal. By age group, the prevalence of high grade prostatic intraepithelial neoplasia were 7.1%, 14.7%, 28.5%, 33.3%, 45.4% and 51.8% for the 3rd, 4th, 5th, 6th, 7th, and 8th decades. CONCLUSIONS: High grade prostatic intraepithelial neoplasia begins to manifest in the Spanish population after the 3rd decade. It is usually focal and peripheral, and significantly increases with age and becomes multifocal. Its prevalence in the Spanish population is moderately lower than in American Caucasians and significantly lower than in Afro-Americans.

Encapsulated hepatocellular carcinoma: radiologic findings and pathologic correlation.

The encapsulated form of hepatocellular carcinoma (HCC) is a pathologic subtype that has been found to occur with variable frequency in typical HCC in Japanese radiological, surgical, and autopsy series. It is well-differentiated tumor that tends to grow slowly and noninvasively, and has a better prognosis than other gross forms of HCC. Among the 73 cases of typical HCC in patients of non-Asian extraction in our files, 11 could be positively identified as encapsulated based on strict pathological criteria. The purpose of this study was to review the radiographic appearance of these encapsulated tumors. Radiographically, the tumors demonstrated a hyperdense rim in 5 of 9 cases with postinfusion computed tomography scans, an anechoic halo in 4 of 6 cases with ultrasonograms, and an avascular rim on the capillary phase in 5 of the 8 cases with angiograms. Encapsulated HCC can be found in non-Asian patients, and the radiographic and pathologic findings are similar to the descriptions in the Japanese series.