p53 gene mutations in radiation-induced thyroid cancer.

Little is known about the role of specific oncogenes and tumor suppressor genes in radiation-induced thyroid cancer (RITC). In thyroid cancer, mutations in the p53 tumor suppressor gene have been largely confined to the more aggressive anaplastic forms. We studied point mutations in the p53 gene in 22 patients exposed in childhood to radiation in the head and neck area who later developed papillary thyroid cancers (RITC). Eighteen thyroid cancer patients without exposure to radiation, selected to match by gender and age the RITC group, were used as the control group. After histological identification, DNA was extracted from paraffin-embedded specimens. Exons 5-8 of p53 were PCR amplified and screened for mutations by single strand conformation polymorphism analysis and cycle sequencing. Four of 22 RITC patients (18%) showed missense point mutations. No missense mutations were found in the cancer control group. The missense mutations in the RITC group occurred at codon 208 in 2 patients, codon 177 in 1, and codon 217 in 1. The mutations were transitions from G to A and C to T. All patients with missense mutations were male and had lymph node involvement. Three of the 4 patients with p53 missense mutations had invasion of the cancer beyond the thyroid capsule compared to 2 of the 17 remaining RITC patients. None of the patients with p53 mutations had distant metastases or recurrence of the tumor. These results suggest that p53 gene point mutations may play a pathogenetic role in some radiation-induced, well differentiated thyroid cancers and in their local spread.

Cellular PSA in benign and malignant prostate.

To determine the relationship of carcinoma of the prostate and cellular production of prostate-specific antigen, cytosol levels of PSA were measured in benign and malignant fresh prostate tissue harvested from radical prostatectomy specimens. Wedge biopsies were taken from benign (N = 21) and malignant (N = 74) prostate tissue and were immediately fixed in liquid nitrogen, and then homogenized and differentially centrifuged, and the cytosol fractions extracted. The remaining specimen was sent for routine pathologic assessment. The Hybritech methodology was used to measure the cytosol PSA and standard protein analysis was used for cytosol protein (CP) measurement. There was a significantly greater concentration of PSA in malignant tissue (P = 0.046). Also, when benign and malignant tissue were available from a single prostate (N = 17), these differences in cytosol PSA were even greater (P = 0.002). In addition, there was no significant difference when serum PSAs from the malignant tissue were ranked according to Gleason score and placed into three different histologic grades (i.e., Gleason scores 2-4, 5-6, and 7-10).

Evaluation of the current incidence of nodal metastasis from prostate cancer.

To determine the influences of transrectal ultrasonography, prostate-specific antigen (PSA), and heightened public awareness of prostate cancer stage at diagnosis, we prospectively evaluated our most recent 173 patients who had a pelvic lymphadenectomy from 1987 to 1991. All patients had clinically localized prostate cancer and underwent bilateral limited pelvic lymph node dissections (N = 173); 19 (10.7%) were found to have nodal metastasis. Pathologic tumor stage and grade information was available for 168 patients who had a simultaneous radical prostatectomy. Clinical T-stage data revealed that only one patient had a T3 lesion. Pathologic T stage showed 7.1% to be T1a (12/168), 4.1% to be T1b (7/168), 13.7% to be T2a (23/168), 34.5% to be T2b (58/168), and 40.5% to be T3 lesions (68/168). Metastatic nodal involvement was not seen in any T1a, T1b, or T2a lesions. A Gleason's score of less than 5 lesions was predictive of no nodal metastasis. The clinical stage was upstaged pathologically in none of the T1a, 16.7% of the clinical T1b, 75% of the T2a, and 73% of the T2b lesions. With regard to serum PSA, 27% of those patients with a level > 20 ng/ml had nodal metastasis (6/22) in this series. Although an elevated PSA was not predictive of tumor nodal metastasis, no patient with a normal PSA had nodal metastasis. Although the distribution of pathologic T stages is similar to that reported in the literature, our low incidence of nodal metastasis may suggest that prostate cancer is being diagnosed earlier.

Anatomic, functional, and pathologic changes from internal ureteral stent placement.

The anatomic, hydrodynamic, functional, and pathologic changes associated with unilateral internal ureteral stenting were evaluated in 20 female canines. Selective glomerular filtration rates (GFR) were measured with technetium 99m diethylenetriamine pentaacetic acid (DTPA) renal scans (N = 14) prior to and several weeks after unilateral internal stent placement. Cystometry and cystography were done at weekly intervals to determine if reflux occurred and to measure the intravesical pressure to produce this reflux (N = 16). Ureteral lumenal capacities of mid 6-cm ureteral segments of stented and unstented ureters were compared. The mid-ureteral lumenal volumes were three times greater in the stented ureters (p < 0.002). There were no significant differences in the selective GFR before and after stenting. Low-pressure vesicoureteral reflux occurred at a mean intravesical pressure of 13.7 cm of water and was present in 84.6 percent (11/13) of the canines whose stents did not migrate or obstruct from encrustation. There were no significant alterations in serum chemistries or blood counts. Fluoroscopic imaging also showed ineffective ureteral peristalsis. This study confirms that internal ureteral stents cause vesicoureteral reflux and significant lumenal dilation without altering renal function.

Evaluation of a new tumor marker for localized prostate cancer.

Adenocarcinoma associated antigen (ACAA) is a large molecular weight protein that is normally found in low serum levels. Recent data have revealed elevations in patients with adenocarcinomas, including prostate cancer. To evaluate the relationship of ACAA levels with prostate cancer, we measured the cytosol content in malignant and nonmalignant prostate tissue and compared these results to those of the standard markers, prostatic acid phosphatase (PAP) and prostatic specific antigen (PSA). Enzyme solid phase immunoassay was used to quantitate PSA and ACAA levels, and the enzymatic method was used to measure PAP. Wedge resection from the right and left posterior lobes of 50 fresh radical retropubic prostatectomy specimens were used for cytosol analysis. All foci of within each prostate gland were carefully mapped by a single pathologist. When all malignant wedges (N = 74) were compared to all the benign wedges (N = 21), only the PSA levels showed significant elevation (p less than 0.02). However, when benign and malignant tissue from the same prostate were available for comparison, both PSA (N = 17) and ACAA (N = 16) showed significant elevations in the cytosol of the malignant tissue (p less than 0.002 and p less than 0.03, respectively). Although not statistically significant, the cytosol PAP did show a consistent trend to be greater in malignant tissue. It appears that there is an association of increased cytosol ACAA and PSA with prostate cancer.

Penile malignant melanoma in association with squamous cell carcinoma of the penis.

We report a case of malignant melanoma of the penis in association with penile squamous cell cancer. Previous regional lymphadenectomy did not prevent subsequent development of regional recurrence. This clinical presentation and the literature are discussed.