p53 alteration in regional lymph node metastases from prostate carcinoma: a marker for progression?

Background: Alterations of the p53 tumor suppressor gene are associated with advanced stage prostate carcinoma. The biologic significance of p53 nuclear accumulation in prostate cancer patients with regional lymph node metastases is uncertain.

Methods: The authors investigated p53 alterations by immunohistochemistry in 220 lymph node positive patients who were treated with radical prostatectomy, bilateral pelvic lymphadenectomy, and androgen deprivation therapy between 1987-1992 at the Mayo Clinic.

Reversibility of prostatic intraepithelial neoplasia: implications for chemoprevention.

High-grade prostatic intraepithelial neoplasia is the most likely precursor of prostatic adenocarcinoma, according to virtually all available evidence. It has a high predictive value as a marker for adenocarcinoma, and its identification in biopsy specimens of the prostate warrants further search for concurrent invasive carcinoma. Androgen deprivation therapy and radiation therapy decrease its prevalence and extent, suggesting a role in chemoprevention.

Genetic and chromosomal alterations in prostatic intraepithelial neoplasia and carcinoma detected by fluorescence in situ hybridization.

Objective: In this review, we discuss the utility of fluorescence in situ hybridization (FISH) in the determination of genetic and chromosomal alterations in prostate cancer specimens. We also discuss the genetic association between prostatic intraepithelial neoplasia (PIN) and adenocarcinoma as detected by FISH and other techniques.

Methods And Results: FISH is a commonly used technique for the determination of gene and chromosome dosage.

Human glandular kallikrein 2 expression in prostate adenocarcinoma and lymph node metastases.

Objectives: To describe the expression of a potential new tumor marker, human glandular kallikrein 2 (hK2), in primary adenocarcinoma and lymph node metastases that may be useful as an adjunct to prostate-specific antigen (PSA) in the diagnosis and monitoring of prostate cancer.

Methods: We evaluated 151 radical prostatectomy specimens removed at Mayo Clinic with node-positive adenocarcinoma to compare cytoplasmic expression of hK2, pro-hK2, and PSA in benign tissue, prostate adenocarcinoma, and lymph node metastases. Monoclonal antibodies for mature hK2 (hK2-G586), pro-hK2 (pro-hK2-G464), and PSA (PSA-773) were used.

Allelic imbalance in the clonal evolution of prostate carcinoma.

Background: To understand better the genetic basis of the clonal evolution of prostate carcinoma, the authors analyzed the pattern of allelic loss in 25 matched primary and metastatic prostate tumors.

Methods: Twenty-five cases were selected from the surgical pathology files of the Mayo Clinic from patients who had undergone radical retropubic prostatectomy and bilateral lymphadenectomy between 1987-1991. All patients had regional lymph node metastases at the time of surgery.

Mutation and expression analysis of the p73 gene in prostate cancer.

Background: p53 is the most highly mutated tumor suppressor gene in human cancers. Recently, p73, a first homologue of p53, was identified and considered to be an imprinted tumor suppressor gene. Thus, we analyzed the possible role of p73 in human prostate cancers.

Natural history of urothelial dysplasia of the bladder.

Urothelial dysplasia is the putative precursor of urothelial carcinoma in situ (CIS) and invasive urothelial carcinoma of the urinary tract. Urothelial dysplasia is frequently identified in patients with urothelial CIS and cancer. However, very little is known about the clinical presentation and natural history of urothelial dysplasia in the absence of urothelial CIS or invasive cancer.

Predictors of cancer progression in T1a prostate adenocarcinoma.

Background: The biologic behavior of T1a prostate adenocarcinoma is variable. A critical issue in the management of patients with T1a prostate adenocarcinoma is to distinguish those who will develop cancer progression from those who will not. Predictive factors that identify those at high risk of cancer progression are needed to stratify patients for treatment.

p53 protein overexpression is associated with increased cell proliferation in patients with locally recurrent prostate carcinoma after radiation therapy.

Background: The biologic changes in recurrent prostate carcinoma following radiation therapy are not fully understood. The authors sought to determine the level of p53 protein overexpression and its association with cellular proliferation (Ki-67 labeling index), glutathione S-transferase-pi (GST-pi) expression, and other clinical pathologic findings in patients with locally persistent prostate carcinoma after radiation therapy.

Methods: The authors investigated p53 nuclear accumulation, cellular proliferation activity (Ki-67 labeling index by digital image analysis), and GST-pi expression in 55 patients with persistent or recurrent prostate carcinoma after radiation therapy.

Overexpression of the wild type p73 gene in human bladder cancer.

p73, a first p53 relative, was recently identified and shown to be monoallelically expressed in a number of different human tissues. To determine the potential role of this gene in human bladder cancer, we investigated p73 expression levels, allelic expression patterns, and analysed p73 mutations in 23 unselected primary invasive bladder cancers with matched normal tissues and in seven bladder cancer cell lines. In a comparison between normal and tumor tissues using quantitative RT-PCR analysis, we found that p73 was overexpressed in 22/23 bladder cancers, sometimes as great as 20-fold.

Clinically unsuspected and undetected (clinical stage t0) prostate cancer diagnosed on random needle biopsy.

Objectives: To describe the findings in 4 patients who underwent radical prostatectomy for clinically undetected and unsuspected prostate cancer detected on random needle biopsy.

Methods: We reviewed the Mayo Clinic Radical Prostatectomy Prostate Cancer Database of 5793 prostatectomies from 1987 to 1997, and identified 4 patients who had prostate cancer detected on random needle biopsy of the prostate with serum prostate-specific antigen (PSA) less than 4 ng/mL and normal digital rectal examination. Each had requested biopsy despite the absence of clinical suspicion of cancer; 3 had normal transrectal ultrasound, and the fourth had a benign hypoechoic lesion contralateral to the cancer.

Androgen receptor expression in prostate cancer lymph node metastases is predictive of outcome after surgery.

Purpose: Androgens mediate the growth of prostate cancer cells. The predictive value of androgen receptor immunostaining in patient outcome is controversial. We studied the expression of androgen receptors in a large series of patients with node positive cancer, and correlated the results with clinical progression and survival.

Androgen receptor expression in prostatic intraepithelial neoplasia and cancer.

Purpose: Androgen receptors are present in virtually all epithelial cells of the prostate, including benign epithelium, high grade prostatic intraepithelial neoplasia and cancer. However, there have been variable results regarding the clinical significance of cells expressing androgen receptors in prostate cancer. We evaluated the predictive accuracy of androgen receptor expression in prostatic intraepithelial neoplasia and cancer for clinical progression and survival in patients with organ confined prostate cancer treated with radical prostatectomy.

Prostatic central zone volume, lower urinary tract symptom severity and peak urinary flow rates in community dwelling men.

Purpose: Previous studies have suggested that central zone prostatic volume may be more strongly correlated with lower urinary tract symptom severity and peak urinary flow rates than total prostatic volume. We determine whether prostatic central zone volume and central zone index volume correlate better with these measures than total prostate volume in an age stratified, community based random sample of healthy white men.

Materials And Methods: A cohort of 474 men were randomly selected from the 2,115 community dwelling men, 40 to 79 years old, who participated in the Olmsted County study of urinary symptoms and health status among men.

Steam heat with an EDTA buffer and protease digestion optimizes immunohistochemical expression of basal cell-specific antikeratin 34betaE12 to discriminate cancer in prostatic epithelium.

In select cases of prostatic carcinoma, antikeratin 34betaE12 immunohistochemical analysis is diagnostically useful for specific labeling of basal cells. This antibody, however, is prone to variability in staining, and the optimal conditions were not, to our knowledge, previously defined. We combined steam heat with EDTA buffer (steam-EDTA) and protease digestion (steam-EDTA + protease) to optimize epitope retrieval of antikeratin 34betaE12 in 42 cases of prostatic cancer.

Subepithelial pelvic hematoma of the kidney clinically mimicking cancer: report of six cases and review of the literature.

Objectives: Renal pelvic subepithelial hematoma is a rare but significant clinical mimic of neoplasm. Investigation and treatment of this diagnostic problem are uncertain.

Methods: We add 6 patients with this entity to the 15 previously published cases.

Overexpression of ornithine decarboxylase in prostate cancer and prostatic fluid in humans.

Prostate cancer (PCA), the most commonly diagnosed cancer in males in the United States, is the second leading cause of cancer-related deaths of males in this country. Because of the poor success rate in the treatment of PCA, an intervention at an early stage may reduce the progression of small carcinoma to large metastatic lesion, thereby reducing PCA-related deaths. Concerted efforts are needed to establish mechanism-based approaches to develop: (a) the markers for early detection of the disease as well as toward monitoring the efficacy of treatment(s); and (b) novel chemopreventive strategies against PCA.

Cystic renal cell carcinoma is cured by resection: a study of 24 cases with long-term followup.

Purpose: The true incidence and biological behavior of cystic renal cell carcinoma are not known. To our knowledge we present the largest series of patients with cystic renal cell carcinoma with long-term followup.

Materials And Methods: We reviewed the Mayo Clinic surgical pathology files of renal cell cancer cases with a cystic component resected from 1969 to 1997, and arbitrarily chose 75% tumor involvement by cysts as a cutoff for inclusion in the study.

Minimal criteria for the diagnosis of prostate cancer on needle biopsy.

Increased clinical screening of men at risk for prostate cancer, and the realization of the benefits of performing multiple biopsies per prostate, have facilitated early detection of malignancy, while presenting the pathologist with a growing array of diagnostic findings. Interpretation of these findings requires discussion of the minimal criteria required for the diagnosis of cancer on needle biopsy within a wide spectrum of related histologic findings. This spectrum includes small acinar proliferations suspicious for but not diagnostic of cancer, benign mimics of cancer, the preinvasive entity of high-grade prostatic intraepithelial neoplasia, and various treatment effects.

Cancer volume of lymph node metastasis predicts progression in prostate cancer.

Clinical outcome is variable in prostate cancer patients with regional lymph node metastasis. We studied 269 patients who had regional lymph node metastasis at the time of radical retropubic prostatectomy and bilateral pelvic lymphadenectomy at the Mayo Clinic between January 1987 and December 1992. Two hundred fifty-three (94%) patients received androgen deprivation therapy within 90 days of radical prostatectomy.

Current evaluation of the tissue localization and diagnostic utility of prostate specific membrane antigen.

Background: Current statistics indicate that prostate carcinoma is the most common form of cancer diagnosed in American men, resulting in the second highest cancer death rate. Early diagnosis and accurate staging are imperative given that there is little effective treatment for metastatic disease, especially after androgen deprivation therapy fails. Identification of new biochemical markers for disease progression will provide important tools for diagnosis and monitoring.

Prostate cancer microvessels: a novel method for three-dimensional reconstruction and analysis.

Background: Studies of prostate cancer microvessels to date have relied on routine two-dimensional images from histologic tissue sections, and there have been no previous reports of three-dimensional (3D) reconstruction and analysis of prostatic microvessels in benign or malignant specimens. Knowledge about the 3D architecture of microvessels would be useful for determining the utility and limitations of two-dimensional (2D) measures, as well as for determining the usefulness of 3D measures to predict pathologic stage and patient outcome in prostate cancer. However, the ability to study microvessels in 3D must first be demonstrated.

Predictors of survival for prostate carcinoma patients treated with salvage radical prostatectomy after radiation therapy.

Background: Salvage radical prostatectomy is a treatment option for patients with recurrent cancer following radiation therapy. This study was conducted to identify predictors of survival for patients treated with salvage radical prostatectomy.

Methods: The authors studied 86 prostate carcinoma patients who underwent salvage radical prostatectomy for locally persistent or recurrent prostate carcinoma at Mayo Clinic between 1967 and 1996.