Biomarker expression in prostatic intraepithelial neoplasia.
OBJECTIVE
This study was conducted to gain a better understanding of the underlying cellular events involved in the development of prostatic intraepithelial neoplasia (PIN) and to clarify the relationship of PIN to invasive prostatic adenocarcinoma (PCa).


METHODS
This article reviews previous studies from our laboratory and others of biomarker expression in PIN and PCa.


RESULTS
The development of PIN is characterized by increased expression of several biomarkers which may influence the proliferative potential of the dysplastic cells. Increased expression of the growth factor receptors P185erbB-2, p180erbB-3, as well as the product of the c-met proto-oncogene is frequently detected in the dysplastic luminal cells as well as malignant cells of the prostate. Likewise, the expression of the nm-23H1 gene product is strongly expressed in dysplastic and malignant cells. Increased proliferative potential of the dysplastic cells is directly reflected by increased expression of PCNA. In contrast to the enhanced expression of the biomarkers associated with proliferation, decreased expression of prostate-specific antigen (PSA), prostatic acid phosphatase (PAP) and Leu 7 by dysplastic luminal cells is indicative of an impairment of the process of cellular differentiation. Aberrant glycosylation as well as the inappropriate expression of glycosylated tumor antigens is demonstrated by enhanced binding of the lectin Ulex europaeus and increased expression of tumor-associated glycoprotein 72 (TAG-72) and the Lewis Y antigen in dysplastic and malignant cells. Finally, enhanced expression of proteolytic enzymes such as cathepsin D and the 72-kD form of collagenase IV by dysplastic cells may represent an integral event in the development of invasive PCa.


CONCLUSIONS
The studies described in this review clearly demonstrate phenotype similarities of PIN to invasive PCa and furthermore support the concept that PIN represents a preinvasive lesion.
Myers
R B
RB
Department of Pathology, University of Alabama at Birmingham 35291-0007, USA.
Grizzle
W E
WE
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D015415:Biomarkers; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D006031:Glycosylation; D006801:Humans; D007983:Lewis Blood Group Antigens / Q000378:metabolism; D008297:Male; D015513:Oncogene Proteins / Q000378:metabolism; D010641:Phenotype; D017430:Prostate-Specific Antigen / Q000097:blood; D019048:Prostatic Intraepithelial Neoplasia / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D017978:Receptors, Growth Factor / Q000096:biosynthesis / Q000235:genetics
D000951:Antigens, Neoplasm; D015415:Biomarkers; D006023:Glycoproteins; D007983:Lewis Blood Group Antigens; C094162:Lewis Y antigen; C000715470:MAS1 protein, human; D015513:Oncogene Proteins; D000090063:Proto-Oncogene Mas; D017978:Receptors, Growth Factor; C047052:tumor-associated antigen 72; D017430:Prostate-Specific Antigen