Trial Information

Analysis of Prostate Cancer Short-Term Cultures Utilizing Molecular Cytogenetic Methods

Prostate cancer is the most common solid tumor in American males and the most common
malignancy among men in Western industrialized countries. Widespread testing for early
detection of prostate cancer utilizing digital rectal examination and prostate specific
antigen (PSA) has led to a significant clinical conundrum. Differentiating organ confined
indolent disease from aggressive cancer has been imperfect. Nonetheless, increased
detection has led to increased radical prostatectomies. A prevailing goal of the
contemporary, ardent research seeks to discover a molecular biomarker for prognostication.

Given the limitations of the current knowledge of the molecular pathology of prostate
cancer, there are several viewpoints regarding the process of tumorigenesis. However, a
generally accepted hypothetical model describes normal prostatic epithelium progressing to a
pre-malignant or low-grade prostatic intraepithelial neoplasia (PIN). Then, after further
genetic alterations, a succession of histologically apparent adenocarcinoma--first confined,
then metastatic, and finally refractory to hormone treatment ensues. Current molecular
research has shown already complex genetics alterations at the high-grade prostatic
intraepithelial neoplasia stage. Thus, invasive disease represents amplification or further
aberration of precursor events. The seminal event or events have not been recognized and
the undiscovered tumor suppressor gene or proto-oncogene may be a principal tumor marker.

The purpose of this study is to identify specific, shared, consistent, chromosomal
rearrangements found in metaphase preparations for short-term cultures of pathologically
identified and scored primary prostate tumors. These, tumor specimens will be obtained from
patients enrolled in protocol (97-C-0147) by the NCI. Fresh tumor, taken from bi-valved
specimens with one half undergoing tissue pathology, will be immediately placed in growth
media and transferred as a coded specimen as a sample from patients selected and enrolled in
protocol (97-C-0147). Informed consent will be obtained by participating investigators in
the NCI protocol. The outcome measurement will be the characterization, or failure of
characterization, of specific, shared consistent, chromosomal rearrangements. Current
molecular cytogenetics technologies, primarily utilizing chromosomal microdissection, will
be employed toward this goal. Ultimately, this research may help to focus further molecular
studies towards the ultimate goal of finding a unique, cancer specific alteration.