Etiology
The specific molecular mechanisms involved in the development and progression of CaP are an area of intense interest in the laboratory. The gene responsible for familial CaP resides on chromosome 1. Several regions of the human genome have been identified as possible areas that harbor tumor suppressor genes that may be involved in CaP. The regions most commonly identified are chromosomes 8p, 10q, 13q, 16q, 17p, and 18q.

Pathology
Over 95% of the cancers of the prostate are adenocarcinomas. Of the other 5%, 90% are transitional cell carcinomas, and the remaining cancers are neuroendocrine (“small cell”) carcinomas or sarcomas. This discussion will address only adenocarcinomas.

The cytologic characteristics of CaP include hyperchromatic, enlarged nuclei with prominent nucleoli. Cytoplasm is often abundant; thus, nuclear-to-cytoplasmic ratios are not often helpful in making a diagnosis of CaP, unlike their usefulness in diagnosing many other neoplasms. Cytoplasm is often slightly blue-tinged or basophilic, which may assist in the diagnosis. The diagnosis of CaP is truly an architectural one.

The basal cell layer is absent in CaP, although it is present in normal glands, BPH glands, and the precursor lesions of CaP. If the diagnosis of CaP is in question, high-molecular-weight keratin immunohistochemical staining is useful, as it preferentially stains basal cells. Absence of staining is thus consistent with CaP.

Prostatic intraepithelial neoplasia (PIN) is the precursor to invasive CaP. The critical distinguishing feature of invasive CaP is that the basal cell layer of the glandular architecture is absent. While PIN has the cytologic characteristics of CaP, the basal cell layer is present. PIN is usually classified into two categories, high grade (HGPIN) and low grade (LGPIN). The clinical importance of this distinction is that, when detected on prostate needle biopsy, HGPIN is usually associated with invasive CaP in approximately 50-80% of cases, whereas LGPIN is associated with invasive CaP only about 20% of the time. Thus, if a patient has needle biopsies showing only HGPIN, a repeat biopsy is critical to exclude the possibility of having missed an invasive cancer.

Sixty to 70 percent of cases of CaP originate in the peripheral zone, while 10-20% originate in the transition zone and 5-10% in the central zone. Radical prostatectomy series often demonstrate multifocal cancers within the prostate, with some variation in tumor grade.