Biomedical subjects

D G Bostwick

Publications and source records attributed to D G Bostwick.

At least 217 records · Page 12Linked to original sources

PubMed1996

Florid cystitis glandularis of intestinal type with mucin extravasation: a mimic of adenocarcinoma.

Six florid examples of cystitis glandularis of intestinal type associated with focal mucin extravasation into the stroma are reported. Several of the cases caused major diagnostic difficulty with regard to their distinction from adenocarcinoma. Five patients had masses that simulated a bladder neoplasm. Patients ranged from 27 to 65 (average 46) years of age and complained of hematuria or irritative symptoms. Four patients were treated only by transurethral resection. One patient underwent partial cystectomy because of an erroneous diagnosis of adenocarcinoma and another total cystectomy because of a neurogenic bladder. Microscopic examination showed numerous glands lined by intestinal type epithelium, conforming to the appearance of the intestinal variant of cystitis glandularis. All cases had at least a minor component of typical cystitis glandularis, and it was prominent in four cases. All six cases had foci of basophilic mucin in the stroma, and this was prominent in four cases. Rounded aggregates of mucin were occasionally surrounded by compressed connective tissue cells, simulating mucinous cysts. In favour of a benign interpretation were the absence of epithelial cells in the extravasated mucin, the lack of atypicality of the cells lining the intestinal type glands in all but one case, a generally orderly distribution of the glands, and their lack of infiltration of the muscularis propria, although they abutted the latter in several cases. Follow-up from 2 to 14 years is available for three of the cases and has been uneventful, the longest follow-up being in the case diagnosed as adenocarcinoma. These cases illustrate the extent to which cystitis glandularis may mimic a neoplasm on gross evaluation and the propensity of mucin extravasation to cause diagnostic difficulty, a finding documented only rarely previously.

Adenocarcinoma↗

PubMed1996

Progression of prostatic intraepithelial neoplasia to early invasive adenocarcinoma.

OBJECTIVE: High-grade prostatic intraepithelial neoplasia is the most likely precursor of adenocarcinoma. This report describes the diagnostic criteria for prostatic intraepithelial neoplasia, its clinical significance, and the evidence suggesting that it progresses to prostatic adenocarcinoma. METHODS: We reviewed the published evidence linking prostatic intraepithelial neoplasia and prostate cancer. RESULTS: Prostatic intraepithelial neoplasia 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. Most studies suggest that, if untreated, prostatic intraepithelial neoplasia will progress to early carcinoma, although only indirect evidence exists to support this hypothesis. Androgen deprivation therapy decreases the prevalence and extent of prostatic intraepithelial neoplasia, suggesting that this form of treatment may play a role in chemoprevention. Prostatic intraepithelial neoplasia does not appear to elevate serum PSA concentration. It is associated with progressive abnormalities of phenotype and genotype which are intermediate between normal prostatic epithelium and cancer, indicating impairment of cell differentiation and regulatory control with advancing stages of prostatic carcinogenesis. CONCLUSION: Virtually all data indicate that high-grade prostatic intraepithelial is premalignant, accounting for most if not all cases of prostate cancer.

Adenocarcinoma↗

PubMed1996

Potential markers of aggressiveness in prostatic intraepithelial neoplasia detected by fluorescence in situ hybridization.

OBJECTIVE: High-grade prostatic intraepithelial neoplasia (PIN) represents the most likely precursor of prostatic adenocarcinoma. In this review, we discuss the utility of different techniques of interphase fluorescence in situ hybridization (FISH) in evaluating the genetic association between PIN and adenocarcinoma. METHODS AND RESULTS: Although the proportion of PIN and prostatic carcinoma foci that have chromosomal anomalies is similar, foci of carcinoma often have more alterations. This supports the hypothesis that PIN is a precursor of carcinoma. In some prostates, however, PIN foci have more alterations than matched carcinoma foci, suggesting that PIN foci can sometimes undergo more extensive chromosome evolution than carcinoma foci. Gain of chromosome 8 is the most common numerical alteration in prostatic carcinoma and PIN foci, and is associated with increasing cancer stage and grade. Thus, genes on chromosome 8 may play a role in the initiation and progression of prostatic carcinoma. One primary tumor focus usually shares chromosomal anomalies with associated lymph node metastases, implying that only one primary lesion acquires genetic alterations that allow it to escape the prostate. CONCLUSIONS: PIN and prostatic carcinoma have similar genetic changes. This supports the hypothesis that PIN is often a precursor of carcinoma. Genes on chromosome 8 may play a role in both initiation and progression of prostatic carcinoma.

Adenocarcinoma↗

PubMed1996

Prospective analysis of the incidence of ipsilateral adrenal metastasis in localized renal cell carcinoma.

PURPOSE: The incidence of ipsilateral adrenal metastasis in renal cell carcinoma was evaluated in a prospective fashion to understand more fully the natural history of this disease. MATERIALS AND METHODS: During a 15-month period 128 radical nephrectomies were performed for stages T1 to T3bN0M0 renal cell carcinoma at our institution. Of these specimens 100 adrenal glands were of sufficient integrity to allow for thin sectioning. RESULTS: Among the 100 adrenal glands 4 adrenal lesions were discovered (2 metastatic renal cell carcinomas and 2 benign adrenal lesions). All 4 lesions were identified preoperatively by computerized tomography or magnetic resonance imaging. CONCLUSIONS: Our prospective investigation demonstrates that the rate of ipsilateral adrenal metastasis from renal cell carcinoma is approximately 2%, and suggests that when the ipsilateral adrenal gland is well visualized and of normal integrity on preoperative magnetic resonance imaging or computerized tomography adrenal sparing nephrectomy may be considered a viable treatment option.

Adrenal Gland Neoplasms↗

PubMed1996

Prediction of capsular perforation and seminal vesicle invasion in prostate cancer.

PURPOSE: Capsular perforation and seminal vesicle invasion are unfavorable prognostic factors in prostate cancer. Accurate preoperative prediction of these factors would be clinically useful for planning treatment, especially in patients being considered for radiation therapy, nerve sparing radical prostatectomy and watchful waiting. However, current methods are imprecise at predicting the presence and extent of these factors. We determined which combination of commonly available preoperative variables provides the best prediction of capsular perforation and seminal vesicle invasion of patients with clinically localized prostate cancer. MATERIALS AND METHODS: We reviewed the preoperative medical records and biopsy findings from 314 patients with clinical stages T1cN0M0 to T2cN0M0 cancer who underwent radical retropubic prostatectomy and bilateral pelvic lymphadenectomy between September 1991 and June 1993. Radical prostatectomy specimens were embedded and evaluated by whole mount sections. RESULTS: Capsular perforation was observed in 104 patients (33.1%) and seminal vesicle invasion was noted in 46(14.6%). Preoperative variables predictive of capsular perforation and seminal vesicle invasion on univariate analysis were serum prostate specific antigen (PSA) concentration, clinical, stage, Gleason primary and secondary patterns, Gleason score, nuclear grade, perineural invasion and percent cancer in the biopsy specimens. On multivariate analysis, independent prognostic factors for capsular perforation and seminal vesicle invasion were PSA, Gleason score and percent cancer in the biopsy specimens. CONCLUSIONS: The combination of serum PSA concentration, Gleason score and percent cancer in the biopsy specimens provides the best prediction of capsular perforation and seminal vesicle invasion. Models based on this combination of factors may be clinically use to stratify patients for nonoperative treatment.

Adenocarcinoma↗

PubMed1996

Analysis of risk factors for progression in patients with pathologically confined prostate cancers after radical retropubic prostatectomy.

PURPOSE: Up to 26% of patients with pathologically organ confined prostate cancer will experience clinical progression after radical prostatectomy. We attempted to identify patients at greatest risk for future clinical failure despite a favorable pathological outcome. MATERIALS AND METHODS: The study group included 904 patients treated with bilateral pelvic lymphadenectomy and radical retropubic prostatectomy for disease confined to the prostate gland. Preoperative serum prostate specific antigen (PSA), clinical stage, pathological grade and stage, and deoxyribonucleic acid (DNA) ploidy were evaluated by multivariate analysis to determine relative value in predicting treatment failure. A prognostic scoring system was created using the regression coefficients from the Cox multivariate model to classify patients further according to risk of progression. RESULTS: Preoperative PSA concentration, clinical stage, grade and DNA ploidy were significant univariate predictors of progression (p < 0.0001), whereas pathological stage was not (p = 0.2). Multivariate analysis identified pathological grade (p < 0.0001), preoperative serum PSA concentration (p = 0.0006) and DNA ploidy (p = 0.0089) as independent predictors of progression. The prognostic scoring system separated the patients into 5 distinct groups. Patients with the lowest score had a 92% progression-free survival rate at 5 years, compared to only 39% of those with the highest scores. CONCLUSIONS: Patients believed to be at higher risk for cancer progression despite having organ confined disease might be targeted for adjuvant therapy and closer surveillance, while those at low risk may be followed less often.

Adult↗

PubMed1996

Fluorescence in situ hybridization analysis of renal oncocytoma reveals frequent loss of chromosomes Y and 1.

PURPOSE: Cytogenetic studies of a small number of renal oncocytomas have indicated that loss of chromosomes 1 and Y may be involved in the pathogenesis of this tumor. To evaluate these observations further we selected paraffin embedded renal oncocytoma specimens from 20 male and 10 female patients for fluorescence in situ hybridization analysis. MATERIALS AND METHODS: Isolated nuclei were prepared from paraffin embedded specimens, and fluorescence in situ hybridization was performed with enumeration probes for chromosomes 1, 12, X and Y. RESULTS: Tumors from 10 male (50%) and 4 female (40%) patients demonstrated chromosomal alterations. Loss of chromosome Y was observed in specimens from all 10 male patients, and loss of chromosome 1 or gain of chromosome 12 was noted in 5 and 2 of these specimens, respectively. Of the 4 female patients with chromosomal abnormalities 2 had loss of chromosome 1, 1 had gain of chromosome 1 and 1 had gain of chromosome 12. CONCLUSIONS: Our results confirm that loss of chromosomes Y and 1 is common in renal oncocytoma, and that the alterations are probably involved in the pathogenesis of this tumor.

Adenoma, Oxyphilic↗

PubMed1996

Interobserver variability in the diagnosis of high-grade prostatic intraepithelial neoplasia and adenocarcinoma.

High-grade prostatic intraepithelial neoplasia (PIN) is a strong predictor of carcinoma when identified in small-needle biopsy specimens. However, the diagnostic variability of PIN is unknown. Eight pathologists reviewed 321 prostatic biopsy specimens to assess the variability of the diagnosis of high-grade PIN and carcinoma. All of the specimens were classified as negative, high-grade PIN, suspicious for high-grade PIN, carcinoma, or suspicious for carcinoma, more than one diagnosis was permitted, except for negative. We compared diagnoses made by two observers by pairing them for negative versus high-grade PIN, negative versus carcinoma, high-grade PIN versus carcinoma, and all diagnostic categories together. Mean kappa coefficient values for 28 interobserver combinations were 0.451, 0.845, 0.669, and 0.482, respectively, for each of the four comparison combinations considered. Our results indicate a high level of agreement, "almost perfect" (kappa = 0.81-1.0) for carcinoma, "moderate" (kappa = 0.41-0.60) for high-grade PIN, and "substantial" (kappa = 0.61-0.81) for high-grade PIN versus carcinoma. We found that variability was related to the level of interest in prostatic pathology, the conditions of the study, the subjective application of diagnostic criteria, and the influence of peers and clinical colleagues.

Adenocarcinoma↗

PubMed1996

Pigment in prostatic epithelium and adenocarcinoma: a potential source of diagnostic confusion with seminal vesicular epithelium.

Granular cytoplasmic pigment is frequently observed in prostatic epithelium, and may cause confusion with ejaculatory ductal and seminal vesicular epithelium. We evaluated the distribution and histochemical and immunohistochemical phenotype of pigment in nine serially sectioned, whole-mounted prostatectomy specimens with carcinoma. Golden yellow-brown pigment was found in prostatic glandular epithelium in eight cases (89%) of nine, varying from inconspicuous and focal to extensive and diffuse. It was usually located in the basal portion of the secretory (lumenal) cell layer, but was also observed throughout the cytoplasm, and rarely seen in basal cells. Stromal pigment was observed in seven cases (78%) of nine and was patchy and inconspicuous. Epithelial pigment was observed throughout the prostate (transition zone, 67%; central zone, 56%; peripheral zone, 89%; and periurethral glands, 56%). Focal pigment was observed in high-grade prostatic intraepithelial neoplasia in seven cases (78%) of nine and one case (11%) of nine cases of adenocarcinoma. The epithelial pigment was histochemically similar to lipofuscin pigment (Fontana-Masson positive, bleached by permanganate reaction, Prussian blue negative, and Ziehl-Neelsen positive); S100 protein immunohistochemical stains were negative. Our results indicate that pigment is frequently present in the prostatic epithelium of all zones, at least focally, and has histochemical similarities to pigment in the seminal vesicular epithelium. Awareness of prostatic epithelial pigment is important, and the differential diagnosis of pigmented epithelium in scant specimens such as those obtained from needle biopsies includes normal and neoplastic prostatic epithelium, seminal vesicle epithelium, and ejaculatory duct epithelium.

Adenocarcinoma↗

PubMed1996

Comparison of fluorescence in situ hybridization analysis of isolated nuclei and routine histological sections from paraffin-embedded prostatic adenocarcinoma specimens.

Fluorescence in situ hybridization (FISH) is a powerful tool for quantitative analysis of chromosomes and genes and can be applied in a variety of specimens, including cell cultures, isolated nuclei from fresh and fixed tissues, and histological tissue sections. However, the results of FISH analysis of isolated nuclei in prostate cancer have not been previously compared with those from histological sections from the paraffin-embedded tissue blocks. To compare these methods, we studied isolated nuclei derived from 50-microns sections and adjacent 5-microns tissue sections from 10 cases of benign nodular hyperplasia of the prostate and 16 cases of prostatic carcinoma. FISH analysis employed centromere-specific probes for chromosomes 7, 8, 11, and 12. In benign tissue, the percentage of nuclei with three or more signals for chromosomes 7, 8, 11, and 12 was less than 3% for both isolated nuclei and tissue sections. However, the percentage of nuclei with no and one signals was less than 8% for isolated nuclei and more than 24% for tissue sections. In prostatic carcinoma, numeric chromosomal anomalies were found in 75% of cases by both FISH methods. However, isolated nuclei had more chromosomal tetrasomy than tissue sections (mean, 9.2 to 11.0% versus 5.1 to 5.6%, respectively). Conversely, intratumor heterogeneity of chromosomal anomalies was identified in 5 cases by FISH analysis of tissue sections but not in isolated nuclei. Cancer ploidy analysis by FISH correlated well with ploidy analysis by flow cytometry, although FISH was more sensitive for aneuploidy. We conclude that FISH analysis of isolated nuclei and histological tissue sections from paraffin blocks are reliable methods for detection of chromosomal anomalies in archival tissue of prostate cancer, although each method has advantages and disadvantages.

Adenocarcinoma↗

PubMed1996

cis-trans lycopene isomers, carotenoids, and retinol in the human prostate.

An evaluation of the Health Professionals Follow-Up Study has detected a lower prostate cancer risk associated with the greater consumption of tomatoes and related food products. Tomatoes are the primary dietary source of lycopene, a non-provitamin A carotenoid with potent antioxidant activity. Our goal was to define the concentrations of lycopene, other carotenoids, and retinol in paired benign and malignant prostate tissue from 25 men, ages 53 to 74, undergoing prostatectomy for localized prostate cancer. The concentrations of specific carotenoids in the benign and malignant prostate tissue from the same subject are highly correlated. Lycopene and all-trans beta-carotene are the predominant carotenoids observed, with means +/- SE of 0.80 +/- 0.08 nmol/g and 0.54 +/- 0.09, respectively. Lycopene concentrations range from 0 to 2.58 nmol/g, and all-trans beta-carotene concentrations range from 0.09 to 1.70 nmol/g. The 9-cis beta-carotene isomer, alpha-carotene, lutein, alpha-cryptoxanthin, zeaxanthin, and beta-cryptoxanthin are consistently detectable in prostate tissue. No significant correlations between the concentration of lycopene and the concentrations of any other carotenoid are observed. In contrast, strong correlations between prostate beta-carotene and alpha-carotene are noted (correlation coefficient, 0.88; P < 0.0001), as are correlations between several other carotenoid pairs, which reflects their similar dietary origins. Mean vitamin A concentration in the prostate is 1.52 nmol/g, with a range of 0.71 to 3.30 nmol/g. We further evaluated tomato-based food products, serum, and prostate tissue for the presence of geometric lycopene isomers using high-performance liquid chromatography with a polymeric C30 reversed phase column. All-trans lycopene accounts for 79 to 91% and cis lycopene isomers for 9 to 21% of total lycopene in tomatoes, tomato paste, and tomato soup. Lycopene concentrations in the serum of men range between 0.60 and 1.9 nmol/ml, with 27 to 42% all-trans lycopene and 58 to 73% cis-isomers distributed among 12 to 13 peaks, depending upon their chromatographic resolution. In striking contrast with foods, all-trans lycopene accounts for only 12 to 21% and cis isomers for 79 to 88% of total lycopene in benign or malignant prostate tissues. cis Isomers of lycopene within the prostate are distributed among 14 to 18 peaks. We conclude that a diverse array of carotenoids are found in the human prostate with significant intra-individual variation. The presence of lycopene in the prostate at concentrations that are biologically active in laboratory studies supports the hypothesis that lycopene may have direct effects within the prostate and contribute to the reduced prostate cancer risk associated with the reduced prostate cancer risk associated with the consumption of tomato-based foods. The future identification and characterization of geometric lycopene isomers may lead to the development of novel agents for chemoprevention studies.

Aged↗

PubMed1996

Prostatic intraepithelial neoplasia (PIN) and other prostatic lesions as risk factors and surrogate endpoints for cancer chemoprevention trials.

The most efficient strategy for chemoprevention clinical trials are short-term studies which focus on surrogate endpoint biomarkers (SEBs) in high-risk target populations. High-grade prostatic intraepithelial neoplasia (PIN) is the most likely precursor of prostate cancer, and is found in a significant number of routine contemporary needle biopsies without cancer. The frequency and extent of PIN are decreased with androgen deprivation therapy, suggesting that it is a suitable endpoint biomarker for modulation. Potential SEBs for screening chemopreventive agents for prostate cancer in short-term Phase II trials include (1) histologic premalignant lesions, such as high-grade PIN; (2) biochemical markers, including prostate-specific antigen (PSA) serum concentration; and (3) morphometric markers, including nuclear texture, shape, and roundness; size and number of nucleoli; and number of apoptotic bodies; (4) proliferation markers, including MIB-1 and PCNA; (5) genetic markers, including nuclear DNA content (ploidy), oncogene c-erbB-2 (HER-2/neu) expression, fluorescence in situ hybridization for chromosome 8; and PSA-producing cells in the blood detected by reverse transcriptase polymerase chain reaction; and (6) differentiation markers, such as microvessel density as a determinant of angiogenesis. Each of these endpoint biomarkers is measured easily and accurately in serum or in tissue specimens such as formalin-fixed, paraffin-embedded needle biopsies, and may be modifiable by intervention. The clinical utility of these biomarkers as modulatable endpoints in prostate cancer chemoprevention needs to be demonstrated in future clinical trials.

Biomarkers↗

PubMed1995

Chromosomal anomalies in prostatic intraepithelial neoplasia and carcinoma detected by fluorescence in situ hybridization.

The pathogenetic relationship between high-grade prostatic intraepithelial neoplasia (PIN), prostatic carcinoma, and metastases is poorly understood. We used fluorescence in situ hybridization (FISH) with centromere-specific probes for chromosomes 7, 8, 10, 12, and Y to evaluate numeric chromosomal anomalies in PIN (68 foci), localized prostatic carcinoma (78 foci), and lymph node metastases (8 foci) in 40 whole-mount radical prostatectomy and pelvic lymphadenectomy specimens. Chromosomal anomalies were found in 50, 51, and 100% of the foci of PIN, carcinoma, and metastases, respectively. The mean numbers of abnormal chromosomes per focus were 0.66 in PIN, 1.09 in carcinoma, and 3.75 in metastases. The most frequent anomaly in PIN was a gain of chromosome 8 (32% of foci), followed by gains of chromosomes 10 (13%), 7 (10%), 12 (4%), and Y (4%). The most frequent anomalies in foci of carcinoma were gains of chromosomes 7 and 8 (28% and 30% of foci, respectively), followed by gains of chromosomes 10 (23%), 12 (9%), and Y (9%). There was a positive correlation of the gain of chromosome 8 with the pathological stage and Gleason score (both P < 0.05). Usually, carcinoma foci contained more anomalies than paired PIN foci, but five prostates contained one or more foci of PIN with more anomalies than carcinoma. Among the cases with metastases, usually one or more foci of the primary tumor shared chromosomal anomalies with the matched metastases. Our results indicate that PIN and prostatic carcinoma foci have similar proportions of chromosomal anomalies, but foci of carcinoma usually have more alterations. This observation supports the hypothesis that PIN is often a precursor of carcinoma, although there are some carcinoma foci that have few or no apparent chromosomal alterations, whereas concurrent PIN foci have multiple alterations. A gain of chromosome 8 was the most common numerical alteration and was associated with increasing cancer stage and grade, suggesting that it may play a role in the initiation and progression of prostatic carcinoma. Usually, one or more foci of the primary tumor shared chromosomal anomalies with associated lymph node metastases, suggesting that, often, just a single focus of carcinoma gives rise to metastases.

Aged↗

PubMed1995

Leiomyosarcoma of the prostate. Report of 23 cases.

BACKGROUND: Leiomyosarcoma of the prostate is a rare neoplasm that accounts for less than 0.1% of prostate malignancies. Previous reports of this neoplasm consisted of single case studies or small series, often combined with cases of rhabdomyosarcoma. The relationship of prognosis with histologic and immunohistochemical findings has not, to the authors' knowledge, been described in a large series of cases, and the efficacy of various treatments is uncertain. METHODS: The authors undertook a clinicopathologic study of all cases of prostate leiomyosarcoma observed at their institution from 1929 to 1994. Twenty-three cases were retrieved from the files of the Department of Pathology, Mayo Clinic (Rochester, MN), and clinical follow-up was available for 14. Immunohistochemical studies, including actin, desmin, S-100 protein, keratin, and vimentin were performed for 18 cases. RESULTS: Patients ranged in age from 41 to 78 years, with a mean of 61 years. Presenting symptoms included urinary obstruction (100%), perineal pain (25%), burning on ejaculation (7%), and weight loss (7%). The neoplasms ranged from 3.3 to 21 cm (mean, 9 cm) in greatest dimension and were often associated with necrosis. Seven tumors were Grade 2, 10 Grade 3 and 6 Grade 4 (Broders' grading system; scale, 1-4). Mitotic figure counts varied from 2 to 24 per 10 high power fields. Fifteen of 15 (100%) cases were immunoreactive for vimentin, 10 of 16 (63%) were immunoreactive for actin, and 3 of 15 (20%) were weakly reactive for desmin. Keratin expression was observed in 4 of 15 cases (27%), and S-100 protein was negative in all cases. Treatment varied, and usually included a combination of radiation therapy, chemotherapy, and radical prostatectomy or cystoprostatecomy. Follow-up ranged from 2 to 72 months, with a mean of 19 months. Ten patients died from tumor 3 to 72 months (mean, 22 months) after diagnosis. Four patients were alive, including three with residual tumor and one without evidence of tumor at 2, 4, 30, and 4.5 months, respectively. Local recurrence occurred in 10 of 11 patients, including 5 who had gross residual tumor present after surgery. Metastases developed up to 40 months after surgery (mean, 10.3 months), and most frequently involved the lungs. CONCLUSIONS: These findings indicate that prostate leiomyosarcoma has a varied histologic appearance ranging from spindled cell neoplasm reminiscent of smooth muscle to pleomorphic sarcoma. Epithelioid features may be present. Most tumors are immunoreactive with antibodies to vimentin and actin, and reactivity with antikeratin antibodies does not exclude the diagnosis of leiomyosarcoma. Prostate leiomyosarcoma has a poor prognosis, although the length of survival is variable. Radical surgery was the treatment of choice in the current series, but complete excision was difficult in most cases and did not result in cure.

Adult↗

PubMed1995

Carcinosarcoma of the prostate. Report of 21 cases.

BACKGROUND: Carcinosarcoma of the prostate is an unusual malignancy characterized by adenocarcinoma intimately admixed with sarcoma. METHODS: The authors reviewed the clinical and pathologic findings of 21 cases of carcinosarcoma of the prostate from the files of the Mayo Clinic. RESULTS: Patient age ranged from 50 to 89 years (mean, 68 years). Ten patients (48%) had a previous diagnosis of prostatic acinar adenocarcinoma 2-73 months (mean, 33 months) before the diagnosis of carcinosarcoma, 8 of whom had received androgen deprivation therapy and/or radiation therapy in the interim. The Gleason score of adenocarcinoma ranged from 7 to 10 (mean, 9; median, 9). The sarcomas consisted of osteosarcoma (13), leiomyosarcoma (5), fibrosarcoma (1), malignant fibrous histiocytoma (1), and rhabdomyosarcoma (1), and the grade of the sarcoma component ranged from 2 to 4 (mean, 4; median, 4). Adenocarcinoma was the dominant histologic pattern in 7 cases and sarcoma in 14. Immunohistochemical staining revealed cytoplasmic reactivity for prostate specific antigen or keratin in 16 of 16 cases in the adenocarcinoma component. The sarcoma component was positive for vimentin in 16 of 16 cases, actin in 8 of 16 (focal in 2), S-100 protein in 2 of 16, and desmin in 1 of 16. At the time of diagnosis of carcinosarcoma, 11 patients had metastases, including 4 with metastatic adenocarcinoma before the diagnosis of carcinosarcoma. Treatment varied, and nonsurgical therapy was ineffective. Sites of metastases included lung (10 cases), bone (7), brain (4), liver (1), and peritoneum (1). Follow-up ranged from 1 to 107 months after the diagnosis of carcinosarcoma (mean, 34 months; median, 10 months). Mean time to tumor progression was 23 months (range, 1-96 months; median, 18 months). Eighteen patients died of carcinosarcoma from 2 to 107 months (mean, 34 months; median, 9.5 months) after diagnosis. Five-year survival was 41%, and 7-year survival was 14%. Progression and survival were not affected by histologic pattern. CONCLUSIONS: Carcinosarcoma of the prostate is an aggressive malignancy, regardless of histologic type.

Aged↗

PubMed1995

Frequent loss of heterozygosity at 7q31.1 in primary prostate cancer is associated with tumor aggressiveness and progression.

Cytogenetic analyses have demonstrated that chromosome region 7q22-32 is commonly altered in prostate adenocarcinomas. In addition, in recent fluorescence in situ hybridization studies, we have observed that aneusomy of chromosome 7 is frequent in prostate cancer and is associated with higher tumor grade, advanced pathological stage, and early prostate cancer death. These findings suggest that genetic alterations of chromosome 7 play a significant role in the development of prostate cancer. To better define the chromosome 7 alterations, PCR analysis of 21 microsatellite loci was performed on 54 paired prostate cancer and control DNAs. Overall, chromosome 7 allelic imbalance was identified in 16 of 54 cases (30%). Allelic imbalances of loci mapped to 7q were observed in 15 of the 16 cases. The allelic imbalances were classified as losses in 15 tumors (28%) and as gains in 1 (2%) by comparative multiplex PCR analysis. The most common site of allelic loss included loci D7S523 and D7S486 at 7q31.1. A comparison with clinicopathological features of the tested tumors revealed that the allelic loss of 7q31.1 correlated with higher tumor grade (P = 0.012) and lymph node metastasis (P = 0.017). These results indicate that 7q31 may be the site of a putative suppressor gene(s) important for the pathogenesis of prostate carcinoma, and that the genetic alterations at 7q31.1 may participate in tumor progression and metastasis.

Alleles↗

PubMed1995

Allelic loss on chromosome 8p12-21 in microdissected prostatic intraepithelial neoplasia.

The development and progression of human prostate cancer is associated with genetic abnormalities in tumor cells. Inactivation of tumor suppressor genes due to allelic loss is thought to be an important mechanism of gene alteration in prostatic neoplasms. In this study we examined allelic loss on chromosome 8p12-21 in microdissected samples of normal prostatic epithelium, high grade prostatic intraepithelial neoplasia (PIN), and invasive prostate carcinoma from the same patients. Tissue microdissection under direct microscopic visualization procures pure populations of cells of interest, including small lesions such as PIN. Among 30 patients with concomitant cancer and PIN, we found loss of heterozygosity on chromosome 8p12-21 in 63% (34 of 54) of foci of PIN examined and 90.6% (29 of 32) of tumors, suggesting that abnormalities on chromosome 8p12-21 may be important in the early stages of prostatic carcinoma development. Several cases in which multiple foci of PIN from the same patient were sampled showed different patterns of allelic loss. Fifty-five % (16 of 29) of the prostate carcinomas contained a potential precursor PIN focus based on allelic loss pattern. Our results are consistent with the hypothesis that PIN arises multifocally within the prostate gland, and that a subset of these lesions progress to become carcinoma.

Alleles↗

PubMed1995

Allelic imbalance in gastric cancer: an affected site on chromosome arm 3p.

In order to detect regions of DNA containing tumor suppressor genes involved in the development of gastric cancer, we performed an allelotype study on 78 gastric adenocarcinomas from a population composed largely of Texan Hispanics and Anglos, two ethnic groups that have a ratio of incidence rates of gastric cancer of approximately 2:1. In total, 42 microsatellite markers were employed, which detected at least one site per arm of each autosome in the human genome. These included several markers linked to known tumor suppressor genes (TP53, APC, DCC, RB1, and BRCA1). Sites showing quantitative allelic imbalance (AI) greater than 30% were located on 3p (36%), 11q (31%), 12q (38%), 13q (33%), 17p near TP53 (74%), and 17q near BRCAI (32%). Among the 22% of cases showing microsatellite instability (MI), a subset (4 of 17) showed instability at 59% or more of sites tested. No ethnic bias was detected in cases showing MI or in cases with AI at sites with rates of AI above 30%. Tumors of the intestinal subtype were significantly more likely than diffuse tumors to show AI at DI3S170 (P = 0.01). A deletion map of chromosome arm 3p was prepared for tumors with AI at D3S1478. These data indicate that a tumor suppressor gene on chromosome arm 3p is involved in the development of a subset of gastric cancers.

Adenocarcinoma↗