Prostate cancer is a significant cause of death in Western countries and is under the strong influence of androgens. The steroid 5alpha-reductase 2 catalyzes the metabolism of testosterone into the more potent androgen dihydrotestosterone in the prostate gland. The enzyme is a target in pharmacological treatment of benign prostatic hyperplasia using specific inhibitors such as finasteride. Makridakis et al. have characterized the V89L and A49T polymorphisms in recombinant expression systems. The L allelic variant has a lower Vmax/Km ratio than the V variant. In the A49T polymorphism, the T variant has an increased Vmax/Km ratio. We performed a population-based case-control study of the impact of the SRD5A2 V89L and A49T polymorphisms on the risk of prostate cancer. We also studied the relation between the genotypes and age at diagnosis, tumor, node, metastasis stage, differentiation grade, prostate specific antigen and heredity. The study included 175 prostate cancer patients and 159 healthy controls that were matched for age. There was an association with SRD5A2 V89L LL genotype and metastases at the time of diagnosis, OR 5.67 (95% CI 1.44-22.30) when adjusted for age, differentiation grade, T-stage and prostate specific antigen. Heterozygous prostate cancer cases that carried the SRD5A2 A49T AT genotype were significantly younger than cases that carried the AA genotype, (mean age 66 years vs 71, P = 0.038). The SRD5A2 V89L and A49T polymorphisms were, however, not associated with altered prostate cancer risk. Further studies of the V89L polymorphism may lead to better understanding of the etiology of prostate cancer metastases.
BACKGROUND: 8-Hydroxydeoxyguanosine (8-oxodG) is the commonly used marker of oxidative stress-derived DNA damage. 8-OxodG formation is regulated by local antioxidant capacity and DNA repair enzyme activity. Earlier studies have reported contradictory data on the function of 8-oxodG as a prognostic factor in different cancer types. METHODS: We assessed pre-operative serum 8-oxodG levels with an enzyme-linked immunosorbent assay in a well-defined series of 173 breast cancer patients. 8-OxodG expression in the nuclei of cancer cells from 150 of these patients was examined by immunohistochemistry. RESULTS: The serum 8-oxodG levels and immunohistochemical 8-oxodG expression were in concordance with each other (P
To report outcomes for 1,111 men treated with iodine-125 brachytherapy (BT) at a single institution.
A total of 1,111 men (median age, 63) were treated with iodine-125 prostate BT for low- or intermediate-risk prostate cancer between March 1999 and November 2008. Median prostate-specific antigen (PSA) level was 5.4 ng/ml (range, 0.9-26.1). T stage was T1c in 66% and T2 in 34% of patients. Gleason score was 6 in 90.1% and 7 or 8 in 9.9% of patients. Neoadjuvant hormonal therapy (2-6 months course) was used in 10.1% of patients and combined external radiotherapy (45 Gy) with BT (110 Gy) in 4.1% (n = 46) of patients. Univariate and multivariate Cox proportional hazards were used to determine predictors of failure.
Median follow-up was 42 months (range, 6-114), but for biochemical freedom from relapse, a minimum PSA test follow-up of 30 months was required (median 54; n = 776). There were 27 failures, yielding an actuarial 7-year disease-free survival rate of 95.2% (96 at risk beyond 84 months). All failures underwent repeat 12-core transrectal ultrasound -guided biopsies, confirming 8 local failures. On multivariate analysis, Gleason score was the only independent predictor of failure (p = 0.001; hazard ratio, 4.8 (1.9-12.4). Median International Prostate Symptom score from 12 to 108 months ranged between 3 and 9. Of the men reporting baseline potency, 82.8% retained satisfactory erectile function beyond 5 years.
Iodine-125 prostate BT is a highly effective treatment option for favorable- and intermediate-risk prostate cancer and is associated with maintenance of good urinary and erectile functions.
PURPOSE: To evaluate long-term overall survival (OS), cancer-specific survival (CSS), clinical progression-free survival (cPFS), and health-related quality of life (HRQoL) following definitive radiotherapy (RT) given to T(1-4p)N(0)M(0) prostate cancer patients provided by a single institution between 1989 and 1996. METHODS AND MATERIALS: We assessed outcome among 203 patients who had completed three-dimensional conformal RT (66 Gy) without hormone treatment and in whom staging by lymphadenectomy had been performed. OS was compared with an age-matched control group from the general population. A cross-sectional, self-report survey of HRQoL was performed among surviving patients. RESULTS: Median observation time was 10 years (range, 1-16 years). Eighty-one percent had high-risk tumors defined as T(3-4) or Gleason score (GS) > or =7B (4+3). Among these, 10-year OS, CSS, and cPFS rates were 52%, 66%, and 39%, respectively. The corresponding fractions in low-risk patients (T(1-2) and GS or =7B.
Estrogens have an important role in the development and progression of breast cancer. 17beta-Hydroxysteroid dehydrogenase type 1 (17HSD1), type 2 (17HSD2), and type 5 (17HSD5) are associated with sex steroid metabolism in normal and cancerous breast tissue. The mRNA expressions of the 17HSD1, 17HSD2, and 17HSD5 enzymes were analyzed in 794 breast carcinoma specimens by using tissue microarrays and normal histologic sections. The results were correlated with the estrogen receptor alpha (ER-alpha) and beta (ER-beta), progesterone receptor, Ki67, and c-erbB-2 expressions analyzed by immunohistochemical techniques and with the Tumor-Node-Metastasis classification, tumor grade, disease-free interval, and survival of the patients. Signals for 17HSD1 mRNA were detected in 16%, 17HSD2 in 25%, and 17HSD5 in 65% of the breast cancer specimens. No association between the 17HSD1, 17HSD2, and 17HSD5 expressions was detected. A significant association was observed between ER-alpha and ER-beta (P = 0.02; odds ratio, 1.96) expressions. There was also a significant inverse association between ER-alpha and 17HSD1 (P = 0.04; odds ratio, 0.53), as well as ER-alpha and 17HSD5 (P = 0.001; odds ratio, 0.35). Patients with tumors expressing 17HSD1 mRNA or protein had significantly shorter overall and disease-free survival than the other patients (P = 0.0010 and 0.0134, log rank). The expression of 17HSD5 was significantly higher in breast tumor specimens than in normal tissue (P = 0.033; odds ratio, 5.56). The group with 17HSD5 overexpression had a worse prognosis than the other patients (P = 0.0146). ER-alpha also associated with survival (P = 0.045). Cox multivariate analyses showed that 17HSD1 mRNA, tumor size, and ER-alpha had independent prognostic significance.
The mRNA expression of 17beta-hydroxysteroid dehydrogenase (17HSD) types 1 and 2 enzymes catalyzing opposite reaction of estrogen metabolism was investigated in colon cancer. Further, the significance of the 17HSD type 2 enzyme as a possible marker of colorectal cancer (CRC) prognosis was studied. In the normal mucosa, 17HSD type 2 mRNA was predominantly expressed in the surface epithelium and in the upper parts of the crypts. In the lamina propria expression was seen in endothelial cells and mononuclear phagocytes. In colorectal tumors, 17HSD type 2 expression was in most cases downregulated. Female patients had significantly more cancers with high 17HSD type 2 mRNA expression (n=11/35; 31%) than male patients (n=3/39; 8%) (P=0.02). We observed a significant impact of 17HSD type 2 mRNA expression on survival in female patients with distal colorectal cancer (n=24), with an overall cumulative 5-year survival rate of 54% in those with low 17HSD type 2 mRNA expression. None of the female patients with high 17HSD type 2 mRNA expression survived (n=11; P=0.0068; log rank 7.32). In male patients, no significant association with survival was observed. Our data provide evidence suggesting that low 17HSD type 2 mRNA expression is an independent marker of favorable prognosis in females with distal colorectal cancer, supporting the presence of gender- and location-related differences in the pathogenesis of colon cancer.
(18)F-fluoride positron emission tomography/computed tomography and bone scintigraphy for diagnosis of bone metastases in newly diagnosed, high-risk prostate cancer patients: study protocol for a multicentre, diagnostic test accuracy study.
For decades, planar bone scintigraphy has been the standard practice for detection of bone metastases in prostate cancer and has been endorsed by recent oncology/urology guidelines. It is a sensitive method with modest specificity. (18)F-fluoride positron emission tomography/computed tomography has shown improved sensitivity and specificity over bone scintigraphy, but because of methodological issues such as retrospective design and verification bias, the existing level of evidence with (18)F-fluoride positron emission tomography/computed tomography is limited. The primary objective is to compare the diagnostic properties of (18)F-fluoride positron emission tomography/computed tomography versus bone scintigraphy on an individual patient basis.
One hundred forty consecutive, high-risk prostate cancer patients will be recruited from several hospitals in Denmark. Sample size was calculated using Hayen's method for diagnostic comparative studies. This study will be conducted in accordance with recommendations of standards for reporting diagnostic accuracy studies. Eligibility criteria comprise the following: 1) biopsy-proven prostate cancer, 2) PSA = 50 ng/ml (equals a prevalence of bone metastasis of ˜ 50% in the study population on bone scintigraphy), 3) patients must be eligible for androgen deprivation therapy, 4) no current or prior cancer (within the past 5 years), 5) ability to comply with imaging procedures, and 6) patients must not receive any investigational drugs. Planar bone scintigraphy and (18)F-fluoride positron emission tomography/computed tomography will be performed within a window of 14 days at baseline. All scans will be repeated after 26 weeks of androgen deprivation therapy, and response of individual lesions will be used for diagnostic classification of the lesions on baseline imaging among responding patients. A response is defined as PSA normalisation or = 80% reduction compared with baseline levels, testosterone below castration levels, no skeletal related events, and no clinical signs of progression. Images are read by blinded nuclear medicine physicians. The protocol is currently recruiting.
To the best of our knowledge, this is one of the largest prospective studies comparing (18)F-fluoride positron emission tomography/computed tomography and bone scintigraphy. It is conducted in full accordance with recommendations for diagnostic accuracy trials. It is intended to provide valid documentation for the use of (18)F-fluoride positron emission tomography/computed tomography for examination of bone metastasis in the staging of prostate cancer.
We evaluated the predictive value of interim positon emission tomography (I-PET) after one course of chemoimmunotherapy in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). One hundred and twelve patients with DLBCL were enrolled. All patients had PET/computed tomography (CT) scans performed after one course of chemotherapy (PET-1). I-PET scans were categorized according to International Harmonization Project criteria (IHP), Deauville 5-point scale (D 5PS) with scores 1-3 considered negative (D 5PS > 3) and D 5PS with scores 1-4 considered negative (D 5PS = 5). Ratios of tumor maximum standardized uptake value (SUVmax) to liver SUVmax were also analyzed. We found no difference in progression-free survival (PFS) between PET-negative and PET-positive patients according to IHP and D 5PS > 3. The 2-year PFS using D 5PS = 5 was 50.9% in the PET-positive group and 84.8% in the PET-negative group (p = 0.002). A tumor/liver SUVmax cut-off of 3.1 to distinguish D 5PS scores of 4 and 5 provided the best prognostic value. PET after one course of chemotherapy was not able to safely discriminate PET-positive and PET-negative patients in different prognostic groups.
To report the initial experience with combined 18F-fluorodeoxyglucose positron emission tomography (FDG PET)/computed tomography (CT) imaging for suspected recurrent papillary differentiated thyroid cancer (DTC) at Sunnybrook Health Sciences Centre (SHSC), Toronto.
Single institution retrospective study.
Consecutive patients from SHSC who underwent FDG PET/CT imaging for suspected recurrent DTC over a period of 2.5 years were identified and their charts reviewed.
Qualitative appraisal of FDG PET/CT imaging in suspected recurrent DTC.
Sixteen patients (14F, 2M) were identified accounting for 17 FDG PET/CT scans. Three scans (18%) in 3 different patients were reported as suspicious for recurrent disease in the neck (1-3 lesions) and were considered "positive". All were subsequently confirmed pathologically (4-13 positive lymph nodes post operatively). Prior conventional imaging was abnormal in two patients. Two patients had an elevated non-stimulated thyroglobulin (TG)
This paper briefly illustrates the basis, rules of application, and present outcome of the current World Health Organization (WHO) classification for neuroendocrine neoplasms. Established in 2010 upon the proposal from the European Neuroendocrine Tumor Society (ENETS), the WHO 2010 fostered some definitional changes (most notably the use of neuroendocrine tumor (NET) instead of carcinoid) and indicated the tools of grading and staging. Specific rules for its application were also defined. The data generated from the use of WHO 2010 classification substantially endorsed its rules and prognostic efficacy. In addition, the application demonstrated some issues, among which are the possible re-definition of the cutoff for grading G1 vs G2, as well as the possible identification of cases with somewhat different clinical behavior within the G3 neuroendocrine cancer class. Overall, since the recent introduction of WHO 2010 grading and staging, it appears wise to keep the current descriptors to avoid unnecessary confusion and to generate comparable data. Homogenous data on large series are ultimately needed to solve such issues.