BP1, a homeoprotein, is significantly expressed in prostate adenocarcinoma and is concordant with prostatic intraepithelial neoplasia

Abstract

BP1 is a member of the homeobox gene superfamily of transcription factors that are essential for early development. Significant mRNA expression and immunohistochemical reactivity of BP1 is present in a majority of breast cancers and in all cases of inflammatory breast cancer. This study attempts to determine whether BP1 expression is detectable in prostate cancer, another hormone dependent solid tumor, and whether this expression correlates with histopathologic and prognostic factors. Paraffin sections from radical prostatectomy cancer specimens and from tissue microarray sections of prostate cancer, obtained from the Prostate Cancer Tissue Registry (NIH), were assayed for BP1 immunoreactivity. Immunoreactivity scoring by two independent pathologists, using a three-tiered system (0, 1 þ , 2 þ ), was recorded and correlated with Gleason scoring and prostatic specific antigen (PSA) biochemical recurrence. Ki-67 (MIB-1) immunoreactivity was performed to assess proliferation. Kappa and Cochran-Mantel-Haenszel statistical analyses were used to assess interobserver agreement and pathobiologic correlations. Significant BP1 immunoreactivity (2 þ ) was identified in approximately 70% of prostatic adenocarcinomas, whether the analysis was performed on tissue sections (50 cases) or tissue microarray platforms (123 cases). BP1 immunoreactivity was seen in o5% of normal acinar cells. The agreement between two separate observers was very good, with kappa-statistics 40.7. In tissue sections, 12 cases with paired carcinoma and prostatic intraepithelial neoplasia (PIN) showed concordance with strong immunoreactivity. Gleason scores or prostatic specific antigen (PSA) biochemical recurrences were not correlated with strong BP1 immunoreactivity. Tumor proliferation, assayed with Ki-67 (MIB-1) immunoreactivity, was higher in cancer cells that were BP1 immunoreactive, relative to those that were BP1 non-reactive. These findings suggest that BP1 is an important upstream factor in the carcinogenic pathway of prostate cancer and that the expression of BP1 may reflect or directly contribute to tumor progression and/or invasion.

DNA methylation of HOXD3 as a marker of prostate cancer progression

“…24,25 For example, overexpression of HOXC6, PAX2, and BP1 have been described in PCa. [26][27][28] We have previously shown that methylation of homeobox genes is a common event in PCa, 14 whereas others have shown similar results in so-called methylation 'hot spots' within HOX loci. 29,30 In particular, we demonstrated methylation of the HOXD3 region in primary PCa and that this methylation leads to gene silencing in DU-145 cells.…”

DLX4 as a prognostic marker for hepatocellular carcinoma

“…Additionally, DLX4 mRNA expression level was an independent prognostic factor for DFS. Schwartz et al suggest that that DLX4 is an important upstream factor in the carcinogenic pathway of prostate cancer and that the expression of DLX4 may reflect or directly contribute to tumor progression and/or invasion [18].…”

BP1, a Potential Biomarker for Breast Cancer Prognosis

“…This led to researchers investigating other potential markers to detect prostate cancer at its early stage. Prostate cancer was examined for activation of BP1 [45]. In this study, significant BP1 immunoreactivity was identified in approximately 70% of prostatic tumors, whether the analysis was performed on tissue sections (50 cases) or tissue microarray platforms (123 cases).…”