Purpose: The nuclear transcription factor nuclear factor-B (NFB) and its inhibitor, IB, regulate the transcription of various genes involved in cell proliferation, adhesion, and survival. The NFB transcription factor complex plays a role in cancer development and progression through its influence on apoptosis. More recently, NFB has been shown to be activated in human and androgen-independent prostate cancer cells. To our knowledge, this is the first study demonstrating the prognostic significance of NFB immunoreactivity in prostate adenocarcinomas (PACs).Experimental Design: Using prostatectomy specimens, we performed immunohistochemical staining for NFB and IB␣ (Santa Cruz Biotechnology) on formalin-fixed, paraffin-embedded sections obtained from 136 patients with PAC. Cytoplasmic and nuclear immunoreactivity was scored for intensity and distribution, and results were correlated with preoperative serum prostate-specific antigen, tumor grade, stage, DNA ploidy (Feulgen spectroscopy), and biochemical disease recurrence.Results: Forty-nine percent of PACs overexpressed cytoplasmic NFB, and 63% showed decreased IB expression. Cytoplasmic NFB overexpression correlated with advanced tumor stage (P ‫؍‬ 0.048), aneuploidy (P ‫؍‬ 0.022), and biochemical disease recurrence (P ‫؍‬ 0.001). When we compared the means for the NFB-positive and -negative subgroups, NFB overexpression correlated with preoperative serum prostate-specific antigen (P ‫؍‬ 0.04) and DNA index (P ‫؍‬ 0.05). Fifteen percent of PACs expressed nuclear NFB, which correlated with high tumor grade (P ‫؍‬ 0.001) and advanced stage (P ‫؍‬ 0.05). Decreased IB␣ expression correlated with high tumor grade (P ‫؍‬ 0.015). On multivariate analysis, tumor stage (P ‫؍‬ 0.043) and NFB overexpression (P ‫؍‬ 0.006) were independent predictors of biochemical recurrence.Conclusion: These results support a role for NFB pathway proteins in the tumorigenesis of PACs. The findings are also consistent with reported experimental studies suggesting a new strategy of combined chemotherapy and specific NFB blockade in decreasing the rate of disease relapse.

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This study prospectively examined whether I.V. lidocaine could affect the return of bowel function after radical prostate surgery. Lidocaine-treated patients had shorter hospital stays, less pain, and faster return of bowel function. In this population, lidocaine infusion can be a useful adjunct in anesthetic management.

HGPIN found in the contemporary extended biopsy does not warrant repeat biopsy. ASAP continues to be associated with a high risk of cancer and requires at least 1 repeat biopsy using the extended biopsy scheme.

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Matrix metalloproteinases (MMPs) are proteolytic enzymes capable of degrading the structural support network for normal and malignant cells, promoting neoplastic cell invasion and metastasis. Tissue inhibitors of metalloproteinases (TIMPs) maintain connective tissue integrity by modulating MMP activity. Formalin-fixed paraffin-embedded tissue sections from 138 prostatic adenocarcinomas (PACs) were immunostained by a combined automated/manual method using monoclonal antibodies against MMP2 and TIMP2. Immunoreactivity was semiquantitatively scored based on stain intensity and distribution, and results were correlated with Gleason grade, pathologic stage, ploidy status, and disease recurrence. One hundred five of 138 (76%) and 113/138 (82%) PACs expressed MMP2 and TIMP2, respectively. Co-expression was observed in 94/138 (68%) of PACs (P ‫؍‬ .01), correlated with advanced tumor stage (P ‫؍‬ .05), and tended to be associated with disease recurrent cases (P ‫؍‬ .07). TIMP2 expression individually correlated with advanced tumor stage (P ‫؍‬ .04) and reached near significance with disease recurrence (P ‫؍‬ .06). MMP2 expression was also more frequent in recurrent PACs, although this value did not reach statistical significance (P ‫؍‬ .07). However, on multivariate analysis, only pathologic stage (P ‫؍‬ .009) and ploidy status (P ‫؍‬ .03) independently predicted disease recurrence. In conclusion, MMP2 and TIMP2 are co-expressed in a majority of PACs and correlate with prognostic variables. Interestingly, contrary to the previously documented anti-tumor effects of TIMPs, TIMP2 expression appears to have a tumorpromoting role in PACs and warrants further investigation. KEY WORDS: Immunohistochemistry, MMP, Prognosis, Prostate cancer, TIMP. Mod Pathol 2003;16(3):198 -205Matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases, degrade the basement membrane and extracellular matrix, facilitating cell migration, tumor invasion, and metastasis (1-5). There are at least 20 human MMPs, divided into the collagenases, gelatinases, stromelysins, and membrane-type MMPs (MT-MMPs; 1-5). Tissue inhibitors of metalloproteinases (TIMPs) are the major endogenous regulators of MMPs and consist of four homologous members (TIMP1-4; 6 -8). TIMPs are multifunctional proteins that inhibit cell invasion in vitro and tumorigenesis and metastasis in vivo (6). Although each TIMP appears capable of inhibiting several MMPs, these proteins exhibit preferential inhibitory capacity; for example, TIMPs1 and 2 selectively inhibit MMP9 and 2, respectively (9). Increased expression of MMPs has been associated with poor prognosis and shortened patient survival in a variety of malignancies including carcinomas of the esophagus (10), stomach (11), colon (12), breast (13), pancreas (14), lung (15), kidney (16), and ovary (17). TIMP expression has been associated with both tumor suppressor or antimetastatic effects and tumor-promoting effects in selected cancers (18 -20

This trial confirms the curative potential of high-dose carboplatin and etoposide in highly refractory germ cell cancer.