P C Walsh

Previous studies have demonstrated familial clustering of prostate cancer. To define the nature of this familial aggregation and to assess whether Mendelian inheritance can explain prostate cancer clustering, proportional hazards and segregation analyses were performed on 691 families ascertained through a single prostate cancer proband. The proportional hazards analyses revealed that two factors, early age at onset of disease in the proband and multiple affected family members, were important determinants of risk of prostate cancer in these families. Furthermore, segregation analyses revealed that this clustering can be best explained by autosomal dominant inheritance of a rare (q = 0.0030) high-risk allele leading to an early onset of prostate cancer. The estimated cumulative risk of prostate cancer for carriers revealed that the allele was highly penetrant: by age 85, 88% of carriers compared to only 5% of noncarriers are projected to be affected with prostate cancer. The best fitting autosomal dominant model further suggested that this inherited form of prostate cancer accounts for a significant proportion of early onset disease but overall is responsible for a small proportion of prostate cancer occurrence (9% by age 85). These data provide evidence that prostate cancer is inherited in Mendelian fashion in a subset of families and provide a foundation for gene mapping studies of heritable prostate cancer. Characterization of genes involved in inherited prostate cancer could provide important insight into the development of this disease in general.

One hundred twenty-five patients with biopsy proved clinical stage A or B prostatic carcinoma were evaluated with biplane transrectal ultrasonography (US) prior to radical prostatectomy. Sonograms were evaluated for capsular transgression of the tumor into the posterior and posterolateral aspects of the glands as manifested by local contour deformity and irregularity or interruption of the periprostatic fat echoes. Correlation of the findings at US with the findings at pathologic examination of the step sections was obtained, and the presence and depth of capsular penetration were assessed. Of the 250 halves or hemispheres of the prostate gland that were evaluated, capsular penetration was seen at pathologic examination in 86. US enabled correct identification of pericapsular tumor spread in 59 of the 86 hemispheres but did not depict pericapsular tumor spread in 27 hemispheres. Absence of pericapsular tumor spread was verified at pathologic examination in 149 of the 164 hemispheres that either did not have tumor or did not show pericapsular tumor spread. Pericapsular tumor spread was incorrectly diagnosed in 15 hemispheres. A positive US diagnosis of pericapsular tumor spread correlated moderately well with the depth of penetration demonstrated at pathologic examination. Transrectal US is an effective noninvasive procedure that demonstrates the presence of prostatic cancer.

The mechanism by which treatment with testosterone produces azoospermia was investigated in adult male rats. Serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were measured in rats treated with testosterone in order to determine whether testosterone in doses which suppressed only LH, and not FSH, would produce atrophy of the germinal epithelium. Rats received injections of testosterone enanthate (TE), (.3, 3, or 30 mg), 3 times weekly for 6 weeks. Low dose TE (.3 mg): 1) decreased mean testis weight by 42%, 2) produced atrophy of the germinal epithelium, and 3) suppressed serum LH but not FSH. High dose TE (3 and 30 mg): 1) did not affect testis weight, 2) did not affect the histology of the germinal epithelium, and 3) did suppress both LH and FSH. It is concluded that testosterone induces germinal atrophy by suppressing serum LH concentrations and subsequent androgen production by the Leydig cells, thereby decreasing the normally high intratesticular levels of androgen which are necessary for maintenance of the germinal epithelium. When these high concentrations of androgen are restored by treatment with pharmacologic doses of testosterone, no disturbance of the germinal epithelium occurs despite suppression of both LH and FSH.

Various benign conditions have been found to cause hypoechoic lesions in the prostate gland, thus mimicking the sonographic appearance of early prostatic cancer. Transrectal sonograms in a large series of patients with biopsy-proved clinical stage B prostatic cancer were retrospectively reviewed to determine the pathologic correlate to benign hypoechoic peripheral zone lesions. Transrectal sonograms demonstrated hypoechoic lesions that did not represent cancer in 25 of 160 patients examined. All lesions were contralateral to the carcinoma. Pathologic correlation was found in 24 of the 25 lesions. The results of this study show that contralateral hypoechoic lesions in patients with pathologically proved prostatic cancer do not necessarily imply bilateral tumor involvement; they accounted for benign lesions that mimicked the sonographic appearance of malignant tumors and thus produced a false-positive rate for cancer in the contralateral lobe of 16% of patients (25 of 160) with clinical stage B cancer.