Prostatic Neoplasms: Lin K

Lin K, Lipsitz R, Miller T, Janakiraman S, Anonymous00225. · Center for Primary Care, Prevention, and Clinical Partnerships, Agency for Healthcare Research and Quality, Rockville, Maryland 20850, USA. · Ann Intern Med. · Pubmed #18678846 links to  free full text

Abstract: BACKGROUND: Prostate cancer is the most common nonskin cancer in men in the United States, and prostate cancer screening has increased in recent years. In 2002, the U.S. Preventive Services Task Force concluded that evidence was insufficient to recommend for or against screening for prostate cancer with prostate-specific antigen (PSA) testing. PURPOSE: To examine new evidence on benefits and harms of screening asymptomatic men for prostate cancer with PSA. DATA SOURCES: English-language articles identified in PubMed and the Cochrane Library (search dates, January 2002 to July 2007), reference lists of retrieved articles, and expert suggestions. STUDY SELECTION: Randomized, controlled trials and meta-analyses of PSA screening and cross-sectional and cohort studies of screening harms and of the natural history of screening-detected cancer were selected to answer the following questions: Does screening for prostate cancer with PSA, as a single-threshold test or as a function of multiple tests over time, decrease morbidity or mortality? What are the magnitude and nature of harms associated with prostate cancer screening, other than overtreatment? What is the natural history of PSA-detected, nonpalpable, localized prostate cancer? DATA EXTRACTION: Studies were reviewed, abstracted, and rated for quality by using predefined U.S. Preventive Services Task Force criteria. DATA SYNTHESIS: No good-quality randomized, controlled trials of screening for prostate cancer have been completed. In 1 cross-sectional and 2 prospective cohort studies of fair to good quality, false-positive PSA screening results caused psychological adverse effects for up to 1 year after the test. The natural history of PSA-detected prostate cancer is poorly understood. LIMITATIONS: Few eligible studies were identified. Long-term adverse effects of false-positive PSA screening test results are unknown. CONCLUSION: Prostate-specific antigen screening is associated with psychological harms, and its potential benefits remain uncertain.

Forootan SS, Wong YC, Dodson A, Wang X, Lin K, Smith PH, Foster CS, Ke Y. · Molecular Pathology Laboratory, School of Cancer Studies, Faculty of Medicine, University of Liverpool, L69 3GA Liverpool, United Kingdom. · Hum Pathol. · Pubmed #17599389 No free full text.

Abstract: The levels of Id-1 (inhibitor of DNA binding or inhibitor of cell differentiation) expression in a series of prostate cell lines and in an archival set of prostate tissues were examined. Western blot analysis showed that the level of Id-1 expressed in the androgen sensitive cell line LNCaP was 1.2 +/- 0.2 times that detected in the benign cell line PNT-2. The level of Id-1 increased further to 1.8 +/- 0.2 and 2.9 +/- 0.3 in the androgen-insensitive cell lines Du-145 and PC-3, respectively. Immunohistochemical staining with Id-1 antibody performed on 113 cases of prostate tissues showed that among the 7 normal cases, 6 (86%) stained either negative or weakly positive whereas only 1 (14%) stained moderately positive. Among the 36 benign prostatic hyperplasia (BPH) samples, 34 (94%) stained either negative or weakly positive; only 1 (3%) stained moderately and 1 (3%) stained strongly. Of the 70 carcinomas, 8 (11.5%) stained weakly, 34 (48.5%) stained moderately, and 28 (40%) stained strongly positive. The intensity of Id-1 staining in carcinomas was significantly stronger than that detected in the normal prostate and BPH (chi(2) test, P < .001) and it was significantly increased as the increasing malignancy of carcinomas measured by Gleason score (chi(2) test, P < .001). The intensity of Id-1 staining was partially associated with the levels of prostate-specific antigen, but not related to the level of androgen receptor. Kaplan-Meier survival curve analysis showed that, similar to Gleason scores, overexpression of Id-1 was significantly associated with the reduced length of patient survival (log-rank test, P = .01). These results suggest that Id-1 is a useful prognostic marker to predict the outcomes of patients with prostate cancer.

Lin K, Lee SP, Cho JS, Reiter RE, DeMarco JJ, Solberg TD. · Department of Radiation Oncology, University of California, Los Angeles, CA 90095, USA. · Brachytherapy. · Pubmed #17284385 No free full text.

Abstract: PURPOSE: Prostate brachytherapy with suture embedded seeds has emerged as a popular technique to reduce seed migration and to improve dosimetry. Various trials have shown improved dosimetry with seed fixity, whereas others have shown no benefit and possible detriment to suture embedded seeds. In order to contribute to the understanding of whether seed stranding improves dosimetry, we present retrospective data from our institution. METHODS AND MATERIALS: We analyzed 80 patients treated between April 29, 2001 and June 19, 2006, receiving I-125 monotherapy for prostate cancer. Brachytherapy patients at the University of California, Los Angeles (UCLA) were initially treated using a transperineal approach with loose seeds. Subsequent to October 26, 2002, all patients were implanted using suture embedded seeds. Dosimetric quantifiers were calculated based on a CT obtained 1-month postimplantation. RESULTS: Dosimetry of patients treated with stranded seeds showed significant improvement. Specifically, the V100 (volume of the prostate receiving 100% of the prescribed dose) improved from 88% to 92% (p<0.05), and the D90 (maximum dose received by 90% of the prostate) improved from 143 to 155 Gy (p<0.05). CONCLUSIONS: At UCLA, the use of suture embedded seeds resulted in a significant improvement in our dosimetric quantifiers. Based upon other published studies, this improvement in dosimetry may translate into improved patient outcomes.

Bee A, Ke Y, Forootan S, Lin K, Beesley C, Forrest SE, Foster CS. · Department of Molecular Pathology, School of Clinical Laboratory Sciences and Royal Liverpool and Broadgreen NHS Trust, University of Liverpool, Liverpool, United Kingdom. · Clin Cancer Res. · Pubmed #16609016 links to  free full text

Abstract: Microquantity differential display analysis of gene expression profiles between benign (PNT2) and malignant (PC3M) human prostate cell lines identified the gene encoding ribosomal protein L19 (RPL19) to be overexpressed in the malignant cells. Northern blot hybridization analysis done on a wide range of human cell lines and tissues confirmed the level of RPL19 mRNA to be 5-fold higher in malignant cell lines and 8-fold higher in malignant tissues, when compared with their benign counterparts. Analysis of RPL19 mRNA expression by in situ hybridization revealed a significant increase of RPL19 expression in a substantial number of prostate cancers. All of the eight normal prostatic tissues were unstained (100%). Of 32 benign prostatic hyperplasia (BPH) tissues, 15 (46.9%) were unstained, 9 (28.1%) stained weakly, and 8 (25%) stained moderately. Among 87 carcinomas, only 7 (8.1%) were unstained, whereas 22 (25.2%) stained weakly, 21 (24.1%) stained moderately, and 37 (42.61%) stained strongly. The intensity of staining of the malignant specimens was significantly higher than that of normal and BPH specimens (chi(2): n = 127, P < 0.001). Gleason scores of the carcinomas correlated with RPL19 expression (chi(2): n = 87, P < 0.001). Kaplan-Meier survival analysis confirmed increased RPL19 expression to be highly predictive of shorter patient survival (P < 0.05), revealing RPL19 to be a sensitive predictor of prostate cancer progression. Expression of this protein could be a valuable marker in prostate cancer diagnosis and patient management.

Forootan SS, Foster CS, Aachi VR, Adamson J, Smith PH, Lin K, Ke Y. · Molecular Pathology Laboratory, School of Clinical Laboratory Sciences, Faculty of Medicine, University of Liverpool, Liverpool L69 3GA, United Kingdom. · Int J Cancer. · Pubmed #16331611 No free full text.

Abstract: To test the hypothesis that expression of osteopontin (OPN), an integrin-binding glycoprotein, can independently predict the potential aggressiveness of prostate cancer, the status of OPN expression in benign and malignant prostate cancer cell lines and tissues was analysed by Western blot and immunohistochemistry. Amongst the four prostate cell lines analysed, the level of OPN expressed in the benign PNT-2 cells was set at 1, the relative level of OPN expressed in the weakly malignant cell line LNCaP was increased to 1.5. In the highly malignant cell lines Du-145 and PC-3, the level of OPN expression was further increased to 2.9 and 4.4, respectively. An increased expression of OPN was also observed in the prostate tissue samples. When the level of OPN in normal tissue was set at 1, its level in benign prostate hyperplasia (BPH) was similar at 0.99 +/- 0.2, whereas the OPN level in the highly malignant carcinoma tissue was greatly increased by nearly 6-fold to 5.9 +/- 0.3. Amongst the 116 cases examined immunocytochemically, of the 10 normal cases, 3 (30%) were unstained and 7 (70%) stained weakly positive (+). Amongst the 36 BPH samples, 32 (89%) stained weakly positive (+) and 4 (11%) were unstained (-). For the 70 carcinomas analysed, 31 (44%) stained strongly positive (+++), 20 (29%) stained moderately positive (++) and 19 (27%) stained weakly positive (+). These results showed that the level of OPN expressed between the normal and the BPH samples was not significantly different (Fisher's exact test, p = 0.16). However, in comparison to that in the BPH samples, the expression of OPN in the carcinoma tissues was significantly increased (Chi-square test, p < 0.0001). Kaplan-Meier survival analysis showed that the increased level of OPN expression was significantly (n = 70, p = 0.03) associated with reduced survival time of the patients. The OPN expression was increased with the increasing Gleason scores of the carcinomas (Chi-square test, p < 0.001). The results in our study support our hypothesis and suggest that the increased OPN level may be involved in the malignant transformation of prostate epithelial cells and OPN expression level is an important determinant for patient survival.

Lin K, Szabo Z, Chin BB, Civelek AC. · Division of Nuclear Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA. · Clin Nucl Med. · Pubmed #10439178 No free full text.

Abstract: PURPOSE: This study evaluated the role of bone scans in managing newly diagnosed, untreated prostate cancer. METHODS: Two hundred seventy consecutive staging bone scans in patients (mean age, 69 years) with newly diagnosed prostate cancer who had serum prostate-specific antigen (PSA) determinations and biopsies between January 1995 and October 1997 were evaluated retrospectively. RESULTS: The bone scans were positive for metastatic bone disease in 24 patients and negative in 246. Serum PSA levels, the number of positive biopsy cores, the extent of tumor in the prostate gland, and Gleason scores were all significantly correlated with scintigraphic bone metastases (P < 0.0001 for each). Of the 177 patients with PSA levels less than 10 ng/ml, three had bone metastases. Bone metastases were found in 2 of 34 patients with PSA levels of 10.1 to 20 ng/ml, in 3 of 29 patients with PSA values of 20.1 to 50 ng/ml, and in 16 of 30 patients with PSA levels greater than 50.1 ng/ml. Only one patient had a bone metastasis when the prostate cancer involved fewer than 2 biopsy cores (1 of 135) or when disease was confined to one lobe (1 of 131), but the incidence increased significantly when the malignancy involved three or more biopsy cores (20 of 114) or disease was present in both prostate lobes (20 of 118). Four of 160 patients with Gleason scores less than 6 had bone metastases, whereas 20 of 110 patients with Gleason scores greater than 7 had bone metastases. CONCLUSIONS: The likelihood of bone metastases is low in patients with newly diagnosed, untreated prostate cancer when the initial PSA level was less than 10 ng/ml, the number of positive biopsy cores was less than 2, tumor was confined to one lobe, or the Gleason score was less than 6. However, none of these criteria can be used to exclude metastatic bone disease. A baseline bone scan is an important staging procedure and should be obtained to provide maximum data for clinical management of the disease.