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Formalin fixation preserves tissue morphology at the expense of macromolecule integrity. Freshly frozen samples are the golden standard for DNA and RNA analyses but require laborious deep-freezing and frozen sectioning for morphological studies. Alternative tissue stabilisation methods are therefore needed. We analysed the preservation of nucleic acids, immunohistochemical staining properties and tissue morphology in paraffinembedded clinical tissue samples fixed with Z7, RCL2, PAXgene, Allprotect and RNAlater. Formalin-fixed and deep-frozen samples were used as controls. Immunohistochemical analyses showed good preservation of antigenicity in all except Allprotect and RNAlater-fixed samples. RNA quality, based on RNA integrity number value by Bioanalyzer, was comparable with freshly frozen samples only in PAXgene-fixed samples. According to quantitative reverse transcriptionpolymerase chain reaction (qRT-PCR) analyses, RNA from PAXgene samples yielded results similar to freshly frozen samples. No difference between fixatives was seen in DNA analyses (PCR and real-time PCR). In conclusion, PAXgene seems to be superior to other molecular fixatives and formaldehyde. [ABSTRACT FROM AUTHOR]

Study Type - Aetiology (cohort) Level of Evidence 2b OBJECTIVE • To describe clinical and histopathological characteristics of Finnish familial prostate cancer (PCa) through a detailed analysis of cases in families. PATIENTS AND METHODS • In total, 202 Finnish families with 617 histopathologically confirmed PCa cases of confirmed genealogy were collected. • Complete clinical data, including age and prostate-specific antigen (PSA) at diagnosis, stage, grade and primary treatment, were gathered. The mean (range) number of affected men per family was 3 (2-8). • All the available diagnostic biopsy samples ( n= 323) were collected and regraded by the same uropathologist. • A population-based cohort of 3011 hospital district Pirkanmaa PCa patients was used as a control group. RESULTS • The mean (range) year of diagnosis of PCa was 1993 (1962-2006) and the mean (range) age at diagnosis was 68 (43-98 years). • The median (range) primary PSA level was 12.0 (0.8-11 000) ng/mL. After regrading, the Gleason score was ≤6 in 38%, 7 in 37% and ≥8 in 25% of men. • The subset of familial PCa men diagnosed after 1995 had higher PSA levels ( P= 9.9 × 10−6) and an earlier age of onset ( P= 1.7 × 10−6) than men in the control group, although there were no differences in cancer-specific survival. CONCLUSIONS • We observed an earlier age of onset and higher PSA in familial PCa. • However, differences between sporadic and familial or hereditary PCa cannot be truly solved until genetic testing of high-risk genes in addition to family history is used to define PCa families. • We also emphasize that, when histological samples are collected over a longer study period, reanalysis of the samples by the same experienced uropathologist should be considered. What's known on the subject? and What does the study add? Previous hospital- or population-based cross-sectional studies comparing the clinical and histopathological features of hereditary, familial and sporadic PCa either reported weak trends or no differences in features measured except the age of onset. In present study we observed higher PSA and earlier age of onset in the subset of 257 familial PCa menin Finnish PCa families. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the performance of human papillomavirus (HPV)‐based screening in the framework of an organised cervical cancer screening programme. Methods: A total of 46 708 women aged 35‐60 years invited to the regional cervical cancer screening programme from 1 January 2012, to 31 December 2014, were enrolled. Overall, 17 770 women were screened by the Abbot RealTime hrHPV test with cytology triage and 15 605 were screened by conventional (Papanicolaou, Pap) cytology. In both groups, women with at least low‐grade squamous intraepithelial lesions were referred directly for colposcopy, whereas HPV‐positive women with borderline or normal cytology were invited to intensified screening in the following year. In the Pap group, the indication for intensified follow‐up was borderline cytology. Results: The attendance rate was similar in the HPV and Pap groups (72% and 71%, respectively). Overall, 6.0% of women in the HPV group vs 6.4% in the Pap group were referred to intensified follow‐up (relative risk 0.94, 95% confidence interval [CI]: 0.87‐1.03). At the index screening years, the relative sensitivity of the HPV test with cytology triage vs conventional screening was 1.64 (95% CI: 1.05‐2.55) for CIN2+ and 2.06 (95% CI: 1.17‐3.41) for CIN3+. The specificity of the hrHPV test with cytology triage for CIN2+ and CIN3+ was equal to that of the Pap screening (99.2% vs 99.2% for CIN2+ and 99.1% vs 99.1% for CIN3+). Conclusions: Due to its high sensitivity and specificity, primary hrHPV testing with cytology triage seems to be acceptable for cervical cancer screening in an organised setting. In routine cervical cancer screening program, primary hrHPV test with cytology triage finds more high‐grade squamous intraepithelial lesions than conventional cytology. [ABSTRACT FROM AUTHOR]

Objective: The effects of blood cholesterol levels on prostate cancer (PCa) prognosis are unclear. This study explored the associations between blood cholesterol levels and PCa clinical characteristics, including Gleason score and tumor, node, metastasis stage, as well as risk of PCa recurrence and death after radical prostatectomy. The association between statin-induced cholesterol decline and PCa prognosis was also studied. Materials and methods: The study cohort consisted of 1314 PCa patients who underwent radical prostatectomy as primary management at the Tampere University Hospital between 1995 and 2009. The follow-up continued until the end of 2016. Results: No associations between cholesterol and PCa severity were found. High-density lipoprotein (HDL) > 1 mmol/l and low-density lipoprotein (LDL) > 3 mmol/l were associated with reduced risk of all-cause death in time-dependent analysis. However, the risk association was short term as neither HDL or LDL measured 3 years earlier had an effect on PCa prognosis. Modest statin-induced cholesterol decline lowered the risk of PCa recurrence. Hazard ratios (95% confidence intervals) by modest total cholesterol and LDL declines were 0.24 (0.09-0.60) and 0.31 (0.11-0.88), respectively. Conclusions: The findings do not support cholesterol as a risk factor for PCa severity or prognosis after prostatectomy. Cholesterol decline by statin treatment was associated with improved recurrence-free survival compared to statin users whose cholesterol did not decline, which supports the importance of controlling for compliance with statin use when estimating the effects of statins in PCa. [ABSTRACT FROM AUTHOR]

Melanoma is a highly metastatic tumour originating from neural crest-derived melanocytes. The aim of this study was to analyse the expression of neuron navigator 3 (NAV3) in relation to membrane type-1 matrix metalloproteinase MMP14, a major regulator of invasion, in 40 primary melanomas, 15 benign naevi and 2 melanoma cell lines. NAV3 copy number changes were found in 18/27 (67%) primary melanomas, so that deletions dominated (16/27 of samples, 59%). NAV3 protein was found to be localized at the leading edge of migrating melanoma cells in vitro. Silencing of NAV3 reduced both melanoma cell migration in 2-dimensional conditions, as well as sprouting in 3-dimensional collagen I. NAV3 protein expression correlated with MMP14 in 26/37 (70%) primary melanomas. NAV3 and MMP14 were co-expressed in all tumours with Breslow thickness <1 mm, in 11/23 of mid-thickness tumours (1–5 mm), but in only 1/6 samples of thick (>5 mm) melanomas. Altogether, NAV3 number changes are frequent in melanomas, and NAV3 and MMP14, while expressed in all thin melanomas, are often downregulated in thicker tumours, suggesting that the lack of both NAV3 and MMP14 favours melanoma progression. [ABSTRACT FROM AUTHOR]

Introduction: In randomized studies, testing for high-risk (HR) human papillomavirus (hrHPV) has been more sensitive than conventional cytology in detecting cervical intraepithelial neoplasia (CIN). The aim of this study was to evaluate the performance of HPV testing in the setting of an organized routine screening program.Material and Methods: Since 2012, 35- to 60-year-old women living in the city of Tampere have been screened with the Abbott RealTime hrHPV test. HPV-negative women are referred to the next screening round in five years. HPV-positive women are triaged with conventional cytology, and women with at least low-grade squamous intraepithelial lesion (LSIL+ ) are referred to colposcopy. The remaining HPV-positive women are referred for re-testing after 12 months, and then all HPV-positive women are referred to colposcopy. The data from the last cohort with cytological screening (screened in 2011) is presented for comparison.Results: A total 5637 (70%) women attended the first round of HPV screening, and 369 were HPV-positive. Of them, 54 women LSIL+ were referred to colposcopy, resulting in 16 CIN2+ lesions found. Of the remaining HPV-positive women, 66% were still positive one year later, and were referred to colposcopy, with 18 additional CIN2+ lesions found. The attendance rate to the last round of cytological screening was 71% (5814 women). Sixty-four women with LSIL+ cytology were referred to colposcopy, and 11 CIN2+ lesions were found. Of the 777 women with borderline cytology and scheduled for reflex screening in the following year, 109 (19%) had ASC-US+ , and 57 underwent colposcopy, resulting in six additional CIN2+ lesions found. The total detection rate of CIN2+ was significantly higher in the HPV-screened cohort (6.0/1000 vs. 2.9/1000, p = 0.015). However, the total colposcopy rate was 4% vs. 2%, respectively (p < 0.001).Conclusion: Human papillomavirus testing also seems to be more sensitive than cytology in detecting CIN2+ lesions in the setting of a routine organized screening program, besides in the context of randomized trials. The problem of an increased colposcopy rate needs to be addressed in the future. [ABSTRACT FROM AUTHOR]

To evaluate the risk of false HPV‐negative results and possible related morphological abnormalities in HPV primary cervical cancer screening. Out of 53,661 HPV‐negative cases, 5469 (10.2%) randomly selected cytology slides were evaluated as a part of the quality assurance protocol. The Bethesda category negative for intraepithelial lesion or malignancy (NILM) in the HPV‐negative cases given was present in 95.4%. Due to cytology other than NILM, 0.4% of cases were referred to colposcopy and 4.2% to the follow‐up in one year. In the follow‐up HPV negativity and NILM cytology was present in 88.3% of attended women. Cases other than HPV negative and NILM were referred to colposcopy. One biopsy‐proven histological HSIL was found in the first round and one in follow‐up screening. More comprehensive genotyping of HSIL cases revealed genotypes 69 and 11. Only two HPV test negative cases with histological HSIL were revealed forming 0.04% of quality control group. In both cases, HPV genotype not included in screening tests was found. According to the results, the primary HPV test with cytology triage is an efficient and specific method for cervical cancer screening despite of the fact that some non‐high‐risk genotypes are missed. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the feasibility of a population‐based screening trial using prostate‐specific antigen (PSA), a kallikrein panel and multiparametric magnetic resonance imaging (MRI) aimed at minimizing overdiagnosis, while retaining mortality benefit. Patients and Methods: Feasibility of the screening algorithm was evaluated in terms of participation, screening test results and cancer detection. A random sample of 400 men aged 65 years was identified from the population registry and invited for screening with three stepwise tests (PSA, kallikrein panel and MRI). Men with PSA levels ≥3 ng/mL were further tested with the kallikrein panel, and those with positive findings (risk >7.5%) were referred for prostate MRI. Men with positive MRI (Prostate Imaging Reporting and Data System [PI‐RADS] score 3–5) had targeted biopsies only. Men with negative MRI, but PSA density ≥0.15 underwent systematic biopsies. Results: Of the 399 men invited, 158 (40%) participated and 27 had PSA levels ≥3 ng/mL (7% of the invited and 17% of the participants). Of these, 22 had a positive kallikrein panel (6% of the invited and 81% of the PSA‐positive men). Finally, 10 men (3% of the invited and 45% of 4Kscore [kallikrein panel]‐positive) had a suspicious MRI finding (PI‐RADS score ≥3) and five were diagnosed with a clinically significant prostate cancer (Gleason Grade Group [GG] ≥2) at fusion biopsy (3% of the participants), with two GG 1 cases (1%). Additional testing (kallikrein panel and MRI) after PSA reduced biopsies by 56%. Conclusion: The findings constitute proof of principle for our screening protocol, as we achieved a substantial detection rate for clinically significant cancer with few clinically insignificant cases. Participation, however, was suboptimal. [ABSTRACT FROM AUTHOR]

Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Gleason score is a strong prognostic factor, but its reproducibility is not optimal. Our data show that multipte perineural invasion and Ki-67 index are signs of early biochemical progression in patients treated with hormonal therapy. OBJECTIVE • To evaluate the prognostic value of histopathological variables and immunostainings of biomarkers enhancer of zeste homologue 2 (EZH2), Ki-67 and minichromosome maintenance protein 7 (MCM7) from core biopsies of hormonally treated patients with prostate cancer. PATIENTS AND METHODS • Biopsies of 247 primarily endocrine-treated patients were analysed for histopathological characteristics and Gleason scores (GS) according to the revised guidelines of International Society of Urologic Pathology (ISUP) consensus conference 2005. • Immunohistochemical stainings were analysed with the aid of digital image analysis. • The prognostic value of the histopathological variables and the biomarkers was analysed with univariate and multivariate Cox regression analysis, with biochemical recurrence as an endpoint. RESULTS • Biomarkers EZH2 (relative risk [RR] 2.0, 95% confidence interval 1.2-3.3), Ki-67 (3.4, 2.1-5.5) and MCM7 (2.4, 1.5-3.9) were significantly associated with progression-free survival in a univariate analysis. • Ki-67 immunostaining index detected high-risk patients with GS of 7 (9.1, 8.0-10.3). • In a multivariate analysis with non-conventional GS groups 5-7 (3 + 4), 7(4 + 3)-8, and 9-10, the independent prognostic markers were pretreatment GS (2.2, 1.5-3.2), prostate-specific antigen (PSA) level (2.1, 1.1-4.2), perineural invasion (PNI) (1.6, 1.2-2.2), and clinical T-stage (cT) (1.9, 1.0-3.7). • Combination of the independent markers (PSA level >20 ng/mL or GS >3 + 4 or PNI >3 or cT >2) yielded best risk stratification (RR 11.6, 10.4-12.7). CONCLUSIONs • GS remains one of the most important prognostic factors in prostate cancer. However, the refined guidelines by ISUP 2005 might have shifted the threshold between low-grade and high-grade cancers from GS 6 vs 7 to GS 3 + 4 vs 4 + 3. • PNI is an independent prognostic marker superior to cT. • Ki-67 is the most useful biomarker in detecting patients with GS = 7 at high risk for progression. [ABSTRACT FROM AUTHOR]

Introduction: Since 2012, cervical cancer screening has been conducted with a primary high-risk human papillomavirus (hrHPV) test and conventional cytology triage in the city of Tampere, Finland. The women who were screened with the hrHPV test in 2012 were invited to participate in the second screening round in 2017. The aim of the present report was to compare the number of colposcopy referrals and the number of histological high-grade squamous intraepithelial lesion (HSIL)+ (cervical intraepithelial neoplasia [CIN2+]) lesions between the first and second screening rounds of women of a specific age group who were screened twice with the hrHPV test.Material and Methods: The primary hrHPV test used was the RealTime hrHPV PCR assay by Abbott. Women with a positive hrHPV test and cytology triage equal to or worse than low-grade squamous intraepithelial lesion or atypical glandular cells, favor neoplasia, were directly referred to colposcopy, whereas hrHPV-positive women with a negative or equivocal cytology triage were re-screened after approximately 12-16 months. hrHPV-negative women were scheduled for re-screening after 5 years. The present report focuses on the cohort of women who were screened twice with the hrHPV test, who were 35-55 years old in 2012, and 40-60 years old in 2017.Results: In all, 8076 women were invited for HPV screening in 2012 and 8331 women were invited for the second round 5 years later, with attendance rates of 70% and 71%, respectively. Of the women who were screened in 2012, 4571 (69%) belonged to the 35- to 55-year age cohort. In 2017, 4807 (73%) of the women aged 40-60 years participated in the screening. In this cohort, 185 (4.0%) colposcopies were performed in the first screening round, compared with 139 (2.9%) in the second round, and the colposcopy rate was 29% smaller in the second round (P = .002). The number of histological HSIL+ cases was 38 (0.8%) during the first screening round and 29 (0.6%) during the second round (P = .220).Conclusions: In the setting of routine organized cervical cancer screening, the initially high colposcopy rate associated with primary HPV screening seems to level off at the second screening round in women who were screened twice with an hrHPV test. [ABSTRACT FROM AUTHOR]

Background: The European Randomized Study of Screening for Prostate Cancer has shown a 20% reduction in prostate cancer (PC) mortality by prostate‐specific antigen–based screening. In addition, screening has been shown to reduce the risk of advanced PC. The objective of the current study was to analyze the impact of screening participation on the incidence of PC by risk group. Methods: The participants in the screening arm of the Finnish trial (31,867 men) were classified according to screening attendance in a time‐dependent fashion. Initially, all men in the screening arm were regarded as nonattenders until the first screening attendance; they then remained in the once‐screened group until the second screen and similarly for the possible third round. The control arm formed the reference group. Follow‐up started at randomization and ended at the time of diagnosis of PC, emigration, or the end of 2015. PC cases were divided into risk groups according to European Association of Urology definitions. Results: The incidence of low‐risk PC increased with the number of screens, whereas no clear relation with participation was noted in the intermediate‐risk and high‐risk cases. For patients with advanced PC, attending screening at least twice was associated with a lower risk. Conclusions: Screening reduces the risk of advanced PC after only 2 screening cycles. A single screen demonstrated no benefit in terms of PC incidence. Repeated screening is necessary to achieve screening advantages. Attending at least 2 rounds of prostate‐specific antigen–based screening is associated with a reduced incidence of advanced prostate cancer. This benefit should be weighed against an excess of low‐risk cancer, which increases with each screen. [ABSTRACT FROM AUTHOR]

Background: The long‐term health‐related quality of life (HRQOL) impacts of PCa screening have not been adequately evaluated. We aimed to compare the generic and disease‐specific health‐related quality of life (HRQOL) among men with prostate cancer in the screening arm with the control arm of the PSA‐based prostate cancer screening trial in up to 15 years of follow‐up. Materials and methods: This study was conducted within population‐based Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC). During 1996‐1999 80,458 men were randomized to the serum prostate‐specific antigen (PSA) screening arm (SA, N = 32 000) and the control arm (CA, N = 48 458). Men in the screening arm were screened at 4‐year intervals until 2007. HRQOL questionnaires were delivered to newly diagnosed prostate cancer patients in the screening and control arm 1996‐2006 (N = 5128) at the time of diagnosis (baseline), at 3‐month, 12‐month and 5, 10, and 15‐year follow‐up. Validated UCLA Prostate Cancer Index (UCLA‐PCI) and RAND 36‐Item Health Survey were used for HRQOL assessment. The data were analyzed with a random effects model for repeated measures. Results: At baseline, men with prostate cancer in the screening arm reported better Sexual Function, as well as less Sexual and Urinary Bother. Long‐term follow‐up revealed slightly higher HRQOL scores in the screening arm in prostate cancer specific measures at 10‐year post diagnosis, but the differences were statistically significant only in Urinary Bother (UCLA‐PCI score 77.9; 95% CI 75.2 to 80.5 vs. 70.9; 95% CI 66.8 to 74.9 P =.005). The generic HRQOL scores were comparable between the trial arms. The overall differences in disease‐specific or generic HRQOL scores by trial arm did not vary during the follow‐up. Conclusion: No major differences were observed in HRQOL in men with prostate cancer between the prostate cancer screening and control arms during five to 15‐year follow‐up. [ABSTRACT FROM AUTHOR]

In prostate cancer (PCa), lower education level is associated with less screening, more advanced stage at diagnosis and worse survival. The aim of this study was to estimate the association between education level and treatment modality and subsequently survival. The 9255 men diagnosed with PCa in the Finnish Randomized Study of Screening for Prostate Cancer were included. Cancer stage, comorbidity, education level and primary treatment modality were extracted from the patient records, the Finnish Cancer Registry, Statistics Finland and the National Institute of Health and Welfare, and these covariates were used in logistic regression (treatment selection) and Cox regression (survival analysis). In high-risk cancers, men with tertiary education were more likely to be treated with radical prostatectomy (odds ratio [OR] = 1.76; 95% confidence interval [CI] = 1.27–2.44) than men with primary education. Men with secondary (OR = 0.57; 95% CI = 0.38–0.84) or tertiary (OR = 0.42; 95% CI = 0.29–0.60) education were managed less frequently with mere hormonal therapy. In locally advanced cases, tertiary education was associated with more curatively aimed therapies and less hormonal therapy (OR for radical prostatectomy = 2.34; 95% CI = 1.49–3.66; OR for radiotherapy = 1.42; 95% CI = 1.09–1.85; OR for hormonal therapy = 0.45; 95% CI = 0.33–0.60). The hazard ratio for PCa death was lower in men with secondary (0.81; 95% CI = 0.69–0.95) and tertiary (0.75; 95% CI = 0.65–0.87) education than in the patients with primary education. When controlled for the cancer risk group, comorbidity and patient's age, low education level is independently associated with less curatively aimed treatment in men with high-risk or locally advanced PCa and subsequently worse prognosis. • In prostate cancer, the lower education level is associated with worse survival. • The primary treatment modality and education level were analysed in 9255 men. • Cancer stage, the patient's age and comorbidity burden were included in analysis. • Men with a higher education level are treated with more radical intention. • Less curatively aimed therapy is likely to influence worse cancer survival. [ABSTRACT FROM AUTHOR]

In contrast to earlier studies which have used modelling to perform cost-effectiveness analysis, this study links data from a randomised controlled trial with register data from nationwide registries to reveal new evidence on costs, effectiveness, and cost-effectiveness of organised mass prostate-cancer screening based on prostate-specific antigen (PSA) testing. Cost-effectiveness analyses were conducted with individual-level data on health-care costs from comprehensive registers and register data on real-world effectiveness from the two arms of the Finnish Randomised Study of Screening for Prostate Cancer (FinRSPC), following 80,149 men from 1996 through 2015. The study examines cost-effectiveness in terms of overall mortality and, in addition, in terms of diagnosed men's mortality from prostate cancer and mortality with but not from prostate cancer. Neither arm of the FinRSPC was clearly more cost-effective in analysis in terms of overall mortality. Organised screening in the FinRSPC could be considered cost-effective in terms of deaths from prostate cancer: averting just over one death per 1000 men screened. However, even with an estimated incremental cost-effectiveness ratio of below 20,000€ per death avoided, this result should not be considered in isolation. This is because mass screening in this trial also resulted in increases in death with, but not from, prostate cancer: with over five additional deaths per 1000 men screened. Analysis of real-world data from the FinRSPC reveals new evidence of the comparative effectiveness of PSA-based screening after 20 years of follow-up, suggesting the possibility of higher mortality, as well as higher healthcare costs, for screening-arm men who have been diagnosed with prostate cancer but who do not die from it. These findings should be corroborated or contradicted by similar analyses using data from other trials, in order to reveal if more diagnosed men have also died in the screening arms of other trials of mass screening for prostate cancer. [ABSTRACT FROM AUTHOR]

Since 2012, testing high‐risk (HR)HPV has been used as the primary screening test for women ≥35 years attending the organized cervical cancer screening program in the city of Tampere. We evaluated the contribution of HPV16/18 genotyping. Data from 2012 and 2013, and the follow‐up samples in 2013 and 2014, respectively, were analyzed. Abbott RealTime High‐Risk HPV test detecting 14 HRHPV genotypes combined with concurrent genotyping for HPV16 and HPV18 was used. HPV was positive in 794 samples out of 11 346 HPV tested women (7%). HPV16/18 was represented in 22% of HPV‐positive cases. Negative cervical cytology (NILM) was reported in 51% of HPV‐positive samples. HPV16/18 genotype was accompanied with 50% of HSIL/ASC‐H cases. The predominance of HPV16/18 in higher grade lesions was even more evident in cervical biopsies as 57% of CIN3 cases were associated with HPV16/18, and only 20% of carcinomas were associated with nonspecified high‐risk (NSHR) genotypes. In agreement with previous studies HPV16/18 genotypes caused higher grade cytological and histological changes/pathologies than NSHR genotypes in primary screening. Nevertheless, the majority of HRHPV genotypes detected in the screened population were nonHPV16/18, and especially within persistent infections, precancerous lesions were found also among women with NSHR genotypes. [ABSTRACT FROM AUTHOR]

Abstract We tested whether intervention with atorvastatin affects the prostate beneficially compared with placebo in men with prostate cancer in a randomized clinical trial. A total of 160 statin-naïve prostate cancer patients scheduled for radical prostatectomy were randomized to use 80 mg atorvastatin or placebo daily from recruitment to surgery for a median of 27 d. Blinding was maintained throughout the trial. In total, 158 men completed the follow-up, with 96% compliance. Overall, atorvastatin did not significantly lower tumor proliferation index Ki-67 or serum prostate-specific antigen (PSA) compared with placebo. In subgroup analyses, after a minimum of 28 d of atorvastatin use, Ki-67 was 14.1% lower compared with placebo (p = 0.056). Among high-grade cases (International Society of Urological Pathology Gleason grade 3 or higher), atorvastatin lowered PSA compared with placebo: median change –0.6 ng/ml; p = 0.024. Intraprostatic inflammation did not differ between the study arms (p = 0.8). Despite a negative overall result showing no effect of statins on Ki67 or PSA overall, in post hoc exploratory analyses, there appeared to be benefit after a minimum duration of 28 d. Further studies are needed to verify this. Patient summary Cholesterol-lowering atorvastatin does not lower prostate cancer proliferation rate compared with placebo overall, but exploratory analyses suggest a benefit in longer exposure. Take Home Message Atorvastatin at a dose of 80mg/d does not significantly change prostate cancer Ki-67 or prostate-specific antigen (PSA) overall compared with placebo in a randomized trial. However, a minimum intervention duration of 28 d lowers Ki-67 by 14%. Among high-grade cases, atorvastatin lowers PSA compared with placebo, [ABSTRACT FROM AUTHOR]

Prostate cancer (PC) screening remains controversial. We investigated whether screening reduces the difference in prostate cancer risk by socioeconomic status (SES). In 1996-2011, a total of 72,139 men from the Finnish Randomized Study of Screening for Prostate Cancer were analyzed. Outcome measures were PC incidence, mortality, and participation in screening. SES indicators were educational level, income, and home ownership status (data obtained from the Statistics Finland registry). The mean duration of follow-up was 12.7 years. Higher SES was associated with a higher incidence of low- to moderate-risk PC but with a lower risk of advanced PC. Higher education was associated with significantly lower PC mortality in both control and screening arms (risk ratio = 0.48-0.69; P < 0.05). Higher income was also associated with lower PC mortality but only in the control arm (risk ratio = 0.45-0.73; P < 0.05). There were no significant differences in SES gradient by arm (Pinteraction = 0.33 and Pinteraction = 0.47 for primary vs. secondary education and primary vs. tertiary education, respectively; Pinteraction = 0.65 and Pinteraction = 0.09 for low vs. intermediate income and low vs. high income, respectively; and Pinteraction = 0.27 among home ownership status strata). Substantial gradients by SES in PC incidence and mortality were observed in the control arm. Higher SES was associated with overdiagnosis of low-risk PC and, conversely, lower risk of incurable PC and lower PC mortality. Special attention should be directed toward recruiting men with low SES to participate in population-based cancer screening. [ABSTRACT FROM AUTHOR]

Background The multicenter European Randomized Study of Screening for Prostate Cancer has shown a 21% reduction in prostate cancer (PC) mortality by prostate-specific antigen-based screening, with substantial overdiagnosis. In the present study, we analyzed the incidence of PC after screening in relation to the number of screening rounds attended in the Finnish section of the trial. Objective To evaluate the possible reduction in PC incidence following completed screening cycles in relation to the number of screening rounds attended. Design, setting, and participants The participants in the screening arm of the Finnish screening trial (29 298 men) were divided into subgroups of men who had participated at one, two, or three screening rounds. A reference group was formed of the 43 151 men in the control arm by selecting age-matched controls for each subgroup of the screening participants. PC cases diagnosed after screening were identified from the Finnish Cancer Registry until the end of 2011. Follow-up of the screened men started 12 mo (365 d) after the last screening attendance and a similar date was assigned to the men in the control arm. Results and limitations A total of 1514 new PCs cases (cumulative incidence 5.2%) were diagnosed among the screened men after the last screening attendance. In the reference group formed from the control arm, 2683 cases (6.2%) occurred. The hazard ratio (HR) for PC among nonparticipants in the screening arm was 0.89 (95% confidence interval [CI] 0.79–0.99) compared with their controls. Among participants, the HR in those who participated once was 1.39 (95% CI 1.22–1.57), among men who participated twice the HR was 0.97 (95% CI 0.86–1.10), and among men screened three times the HR was 0.57 (95% CI 0.49–0.68). A limitation of the study was that the comparison by attendance is not based on randomization. Conclusions The postscreening PC incidence is reduced after attending three screening rounds, but not after only one or two rounds. Thus, the increased cancer detection at screening is compensated by a subsequent risk reduction only after repeated screening cycles. Patient summary The results of the study indicate that at least three prostate-specific antigen-based screening cycles are needed to reduce subsequent prostate cancer incidence. [ABSTRACT FROM AUTHOR]

Background: Individually submitted prostatic needle biopsies are recommended by most guidelines because of their potential advantage in terms of core quality. However, unspecified bilateral biopsies are commonly submitted in many centers. The length of the core is the key quality indicator of prostate biopsies. Because there are few recent publications comparing the quality of 12 site-designated biopsies versus pooled biopsies, we compared the lengths of the biopsies obtained by both methods. Methods: The material was obtained from 471 consecutive subjects who underwent prostatic needle biopsy in the Tampere University Hospital district between January and June 2013. Biopsies from 344 subjects fulfilled the inclusion criteria. The total number of cores obtained was 4047. The core lengths were measured on microscope slides. Extraprostatic tissue was subtracted from the core length. Results: The aggregate lengths observed were 129.5 ± 21.8 mm (mean ± SD) for site-designated cores and 136.9 ± 26.4 mm for pooled cores (p = 0.09). The length of the core was 10.8 ± 1.8 mm for site-designated cores and 11.4 ± 2.2 mm for pooled cores (p = 0.87). The median length for pooled cores was 11 mm (range 5 mm - 18 mm). For individual site-designated cores, the median length was 11 mm (range 7 mm -15 mm). The core length was not correlated with the number of cores embedded into one paraffin block (r = 0.015). There was no significant difference in cancer detection rate (p = 0.62). Conclusions: Our results suggest that unspecified bilateral biopsies do not automatically lead to reduced core length. We conclude that carefully embedded multiple (three to nine) cores per block may yield cores of equal quality in a more cost-efficient way and that current guidelines favoring individually submitted cores may be too strict. [ABSTRACT FROM AUTHOR]

Background: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) usually presents in middle aged men and shows an indolent clinical behavior. However, up to 30% of the patients present a secondary transformation into aggressive diffuse large B cell lymphoma (DLBCL). The aim of the present study was to characterize morphology and immunophenotype of this kind of DLBCL in detail and compare it with conventional DLBCL. Methods: Morphology and immunophenotype of 33 cases of NLPHL with simultaneous or sequential transformation into DLBCL were investigated. These cases were compared with 41 de novo DLBCL in Finnish men. Results: The majority of cases exhibited different immunophenotypes in the NLPHL and the DLBCL components. The immunophenotype of the DLBCL secondary to NLPHL was heterogeneous. However, BCL6, EMA, CD75 and J-chain were usually expressed in both components (≥73% positive). Overall, the NLPHL component was more frequently positive for EMA, CD75 and J-chain than the DLBCL component. In contrast, B cell markers, CD10 and BCL2, were more frequently expressed and were expressed at higher levels in the DLBCL component than in the NLPHL component. In the independent series of de novo DLBCL 4 cases could be identified with a growth pattern and immunophenotype that suggested that they had arisen secondarily from NLPHL. Conclusions: The morphology and immunophenotype of DLBCL arisen from NLPHL is heterogeneous. Further characterization of the particular molecular features of this subgroup is warranted to be able to better identify these cases among conventional DLBCL. [ABSTRACT FROM AUTHOR]

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) usually presents in middle aged men and shows an indolent clinical behavior. However, up to 30% of the patients present a secondary transformation into aggressive diffuse large B cell lymphoma (DLBCL). The aim of the present study was to characterize morphology and immunophenotype of this kind of DLBCL in detail and compare it with conventional DLBCL. Methods Morphology and immunophenotype of 33 cases of NLPHL with simultaneous or sequential transformation into DLBCL were investigated. These cases were compared with 41 de novo DLBCL in Finnish men. Results The majority of cases exhibited different immunophenotypes in the NLPHL and the DLBCL components. The immunophenotype of the DLBCL secondary to NLPHL was heterogeneous. However, BCL6, EMA, CD75 and J-chain were usually expressed in both components (≥73% positive). Overall, the NLPHL component was more frequently positive for EMA, CD75 and J-chain than the DLBCL component. In contrast, B cell markers, CD10 and BCL2, were more frequently expressed and were expressed at higher levels in the DLBCL component than in the NLPHL component. In the independent series of de novo DLBCL 4 cases could be identified with a growth pattern and immunophenotype that suggested that they had arisen secondarily from NLPHL. Conclusions The morphology and immunophenotype of DLBCL arisen from NLPHL is heterogeneous. Further characterization of the particular molecular features of this subgroup is warranted to be able to better identify these cases among conventional DLBCL. [ABSTRACT FROM AUTHOR]

Objective • To evaluate imaging methods and prognoses between small renal cell carcinomas (RCCs) and larger tumours according to the era of diagnostics. Patients and Methods • In all, 784 consecutive patients diagnosed with RCC between 1964 and 1997 at the Pirkanmaa Hospital District in Finland were included. • Patients were divided into two groups: tumours of ≤3.0 and >3.0 cm in diameter. • Prognosis was analysed according to the era of diagnostics: (i) pre-computed tomography (CT) and pre-ultrasound (US), (ii) US era and (iii) CT era. Results • Small tumours became more common: in the pre-CT and pre-US era, only 4.4% of tumours were small; however, in the CT era 16% were small tumours. • More diagnostic methods were used in studying small tumours. • CT proved to be the most reliable method, although it was actually better at diagnosing large tumours. • Relapses occurred less frequently among patients with small tumours; more than half of the tumours that developed distant metastases (16.0%) already evinced them at the time of diagnosis. There were no relapses after 14 years of follow-up among small tumours, whereas large tumours relapsed within that time. RCC was the cause of death in 14.9% of patients with small tumours vs 50.7% with large tumours. • The best prognosis was among patients with small tumours diagnosed with CT. Conclusion • Among patients with small tumours, prognosis has improved along with better diagnostics, although some showed relapse during a surveillance period of up to 14 years. [ABSTRACT FROM AUTHOR]

Objective To assess whether histological signs of inflammation are associated with an increased risk of subsequent prostate cancer ( PCa) in men with elevated serum prostate-specific antigen ( PSA) concentrations and benign initial biopsy., Materials and Methods Study subjects were men aged 54-67 years with an elevated PSA (≥4 ng/mL or 3-4 ng/mL and free to total PSA ratio ≤0.16 or positive digital rectal examination), but a benign biopsy result within the Finnish population-based randomised screening trial for PCa, which started in 1996., A total of 293 prostate biopsies without PCa or suspicion of malignancy from the first screening round in the Tampere centre were re-evaluated by a uropathologist to assess histological inflammation., Results of the subsequent screening rounds were obtained from the trial database and PCa diagnoses made outside the screening were obtained from the Finnish Cancer Registry., The median length of follow-up was 10.5 years., Cox regression analysis was used to assess PCa risk after the initial benign biopsy., Results Histological inflammation was found in 66% of the biopsies., Subjects with inflammation at the biopsy had a slightly lower PCa risk in the second screening round (18 vs 27%, rate ratio 0.69, 95% confidence interval [ CI] 0.35-1.34) relative to men without inflammation. In further follow-up, the PCa risk remained nonsignificantly lower (hazard ratio [ HR] 0.71, CI 0.46-1.10; P = 0.13). The risk was not appreciably affected by adjustment for age, PSA, prostate volume and family history of PCa ( HR 0.67, CI 0.42-1.07; P = 0.092)., Conclusions Histological inflammation in a prostate biopsy among men with an initial false-positive screening test was not associated with an increased risk of subsequent PCa, but instead with a decreased risk which was of borderline significance., Inflammation in prostate biopsy is not a useful risk indicator in PCa screening. [ABSTRACT FROM AUTHOR]

Background Prostate cancer (PC) screening with prostate-specific antigen (PSA) has been shown to decrease PC mortality by the European Randomized Study of Screening for Prostate Cancer (ERSPC). We evaluated mortality results in the Finnish Prostate Cancer Screening Trial, the largest component of ERSPC. The primary endpoint was PC-specific mortality. Methods A total of 80 144 men were identified from the population registry and randomized to either a screening arm (SA) or a control arm (CA). Men in the SA were invited to serum PSA determination up to three times with a 4-year interval between each scan and referred to biopsy if the PSA concentration was greater than or equal to 4.0rig/ mL or 3.0 to 3.99ng/mL with a free/total PSA ratio less than or equal to 16%. Men in the CA received usual care. The analysis covers follow-up to 12 years from randomization for all men. Hazard ratios (HRs) were estimated for incidence and mortality using Cox proportional hazard model. All statistical tests were two-sided. Results PC incidence was 8.8 per 1000 person-years in the SA and 6.6 in the CA (HR = 1.34, 95% confidence interval [CI] = 1.27 to 1.40). The incidence of advanced PC was lower in the SA vs CA arm (1.2 vs 1.6, respectively; HR = 0.73, 95% CI = 0.64 to 0.82; P< .001). For PC mortality, no statistically significant difference was observed between the SA and CA (HR = 0.85, 95% CI = 0.69 to 1.04) (with intention-to-screen analysis).To avoid one PC death, we needed to invite 1199 men to screening and to detect 25 PCs. We observed no difference in all-cause mortality between trial arms. Conclusions At 12 years, a relatively conservative screening protocol produced a small, non-statistically significant PC-specific mortality reduction in the Finnish trial, at the cost of moderate overdiagnosis. [ABSTRACT FROM AUTHOR]

The human CYP19A1 gene is expressed in various tissues by the use of tissue-specific promoters, whereas the rodent cyp19a1 gene is expressed mainly in the gonads and brain. We generated a transgenic mouse model containing a >100-kb 5' region of human CYP19A1 gene connected to a luciferase reporter gene. The luciferase activity in mouse tissues mimicked the CYP19A1 gene expression pattern in humans. Interestingly, the reporter gene activity was 16 and 160 times higher in the urinary bladder and seminal vesicles, respectively, as compared with the activity in the testis. Accordingly, CYP19A1 gene and P450arom protein expression was detected in those human tissues. Moreover, the data revealed that the expression of CYP19A1 gene is driven by promoters PII, I.4, and I.3 in the seminal vesicles, and by promoters PII and I.4 in the urinary bladder. Furthermore, the reporter gene expression in the seminal vesicles was androgen dependent: Castration decreased the expression ~20 times, and testosterone treatment restored it to the level of an intact mouse. This reporter mouse model facilitates studies of tissue-specific regulation of the human CYP19A1 gene, and our data provide evidence for seminal vesicles as important sites for estrogen production in males. [ABSTRACT FROM AUTHOR]

Abstract: Background: Population-based screening for prostate cancer (PCa) has used serum prostate-specific antigen (PSA) since the early 1990s. However, the efficacy could be affected by screening interval, age ranges of screening, attendance, and contamination of the control group in randomised controlled trials. Objective: Assess the impact of the above-mentioned factors on screening efficacy. Design, setting, and participants: Parameters pertaining to the natural history of PCa and sensitivity were estimated using data from the Finnish quadrennial screening program starting at 55 yr of age and terminating at 71 yr of age and comprising 80 458 men (32 000 in the screening arm and 48 458 in the control arm). We performed Markov decision analyses for different screening policies with a simulated 25-yr follow-up. Intervention: PSA screening. Measurements: The impact of different interscreening intervals and target age ranges on advanced PCa (stage III or worse) and PCa mortality was assessed. Results and limitations: With 65% attendance and 20% contamination, as in the Finnish trial, screening would result in an 11.1% (95% confidence interval [CI], 9.1–13.3%) reduction in advanced cancers and a 7.3% (95% CI, 5.3–9.7%) reduction in PCa death, with corresponding absolute risk difference of 2.6% (95% CI, 1.9–3.5%) and 1.8% (95% CI, 1.4–2.2%), respectively. Numbers needed to screen were 385 to prevent one case of advanced PCa and 556 to prevent one PCa death at 25 yr. Those figures remained similar from 12 yr onwards. Reduction in advanced PCa increased to 40% with annual screening and to 24% with biennial screening. When the age at screening initiation was increased by 5 yr, the benefit was reduced by 9% with annual screening and by 3% with biennial screening. Conclusions: We predicted the impact of basic screening characteristics on the benefit of the program. The screening interval (1–4 yr) had a greater impact on mortality reduction than did the age at start of screening (55–65 yr). Clinical trial registration: International Standard Randomised Controlled Trial Number (ISRCTN): ISRCTN49127736. [Copyright &y& Elsevier]

Expression of fibroblast growth factor 8 (FGF-8) is commonly increased in prostate cancer. Experimental studies have provided evidence that it plays a role in prostate tumorigenesis and tumor progression. To study how increased FGF-8 affects the prostate, we generated and analyzed transgenic (TG) mice expressing FGF-8b under the probasin promoter that targets expression to prostate epithelium. Prostates of the TG mice showed an increased size and changes in stromal and epithelialmorphology progressing fromatypia and prostatic intraepithelial neoplasia (mouse PIN, mPIN) lesions to tumors with highly variable phenotype bearing features of adenocarcinoma, carcinosarcoma, and sarcoma. The development of mPIN lesions was preceded by formation of activated stroma containing increased proportion of fibroblastic cells, rich vasculature, and inflammation. The association between advancing stromal and epithelial alterations was statistically significant. Microarray analysis and validation with quantitative polymerase chain reaction revealed that expression of osteopontin and connective tissue growth factor was markedly upregulated in TG mouse prostates compared with wild type prostates. Androgen receptor staining was decreased in transformed epithelium and in hypercellular stroma but strongly increased in the sarcoma-like lesions. In conclusion, our data demonstrate that disruption of FGF signaling pathways by increased epithelial production of FGF-8b leads to strongly activated and atypical stroma, which precedes development of mPIN lesions and prostate cancer with mixed features of adenocarcinoma and sarcoma in the prostates of TG mice. The results suggest that increased FGF-8 in human prostate may also contribute to prostate tumorigenesis by stromal activation. [ABSTRACT FROM AUTHOR]

Objective. The long-term survival of renal cell cancer (RCC) patients is not reported in the recent literature. This study evaluated the significance of known clinical prognostic factors and long-term survival in a large centrally treated Finnish RCC population. Material and methods. In 948 patients diagnosed between 1964 and 1997 the relative overall survival (OS) was calculated up to 25 years by Bayesian analysis and the life-table method. The effect of gender, age, cancer stage, TNM (tumour, node, metastasis) class, Fuhrman's grade, symptoms and year of diagnosis was studied. Results. Women and patients aged 40–49 years had better survival. Stage, TNM class and grade proved relevant for prognosis. The relative 5-year overall survival was 88%, 63%, 65% and 15% in stages I–IV, respectively. Asymptomatic patients had better survival, their median survival being 8.1 years as against 9.1 years in patients with local symptoms and only 1.7 years in patients with systemic symptoms. The year of diagnosis was not significant in prognosis. Conclusions. The most important explanatory factors were stage, age and clinical presentation of the tumour. RCC patients showed diminishing overall survival in the follow-up, with no plateau; almost 57% of patients developed local recurrence or distant metastases even after a very long disease-free interval. [ABSTRACT FROM AUTHOR]

Abstract: Background: Prostate-specific antigen (PSA) based screening for prostate cancer (PCa) has been shown to reduce prostate specific mortality by 20% in an intention to screen (ITS) analysis in a randomised trial (European Randomised Study of Screening for Prostate Cancer [ERSPC]). This effect may be diluted by nonattendance in men randomised to the screening arm and contamination in men randomised to the control arm. Objective: To assess the magnitude of the PCa-specific mortality reduction after adjustment for nonattendance and contamination. Design, setting, and participants: We analysed the occurrence of PCa deaths during an average follow-up of 9 yr in 162 243 men 55–69 yr of age randomised in seven participating centres of the ERSPC. Centres were also grouped according to the type of randomisation (ie, before or after informed written consent). Intervention: Nonattendance was defined as nonattending the initial screening round in ERSPC. The estimate of contamination was based on PSA use in controls in ERSPC Rotterdam. Measurements: Relative risks (RRs) with 95% confidence intervals (CIs) were compared between an ITS analysis and analyses adjusting for nonattendance and contamination using a statistical method developed for this purpose. Results and limitations: In the ITS analysis, the RR of PCa death in men allocated to the intervention arm relative to the control arm was 0.80 (95% CI, 0.68–0.96). Adjustment for nonattendance resulted in a RR of 0.73 (95% CI, 0.58–0.93), and additional adjustment for contamination using two different estimates led to estimated reductions of 0.69 (95% CI, 0.51–0.92) to 0.71 (95% CI, 0.55–0.93), respectively. Contamination data were obtained through extrapolation of single-centre data. No heterogeneity was found between the groups of centres. Conclusions: PSA screening reduces the risk of dying of PCa by up to 31% in men actually screened. This benefit should be weighed against a degree of overdiagnosis and overtreatment inherent in PCa screening. [Copyright &y& Elsevier]

Simple Summary: A prognostic index for predicting survival of localized prostate cancer (PCa) up to 15 and 20 years was developed. The prognostic index performed well for predicting PCa survival among screened and non-screened men. The performance of the prediction model was superior to the European Association of Urology (EAU) risk groups as well as a modified cancer of prostate risk assessment (CAPRA) risk score. We further constructed a simplified risk score in an unscreened population, using the three most relevant predictors. The simplified risk score was applied to predict PCa survival at 10 years from diagnosis to provide more accurate risk estimation as the basis for decision making. We developed and validated a prognostic index to predict survival from prostate cancer (PCa) based on the Finnish randomized screening trial (FinRSPC). Men diagnosed with localized PCa (N = 7042) were included. European Association of Urology risk groups were defined. The follow-up was divided into three periods (0–3, 3–9 and 9–20 years) for development and two corresponding validation periods (3–6 and 9–15 years). A multivariable complementary log–log regression model was used to calculate the full prognostic index. Predicted cause-specific survival at 10 years from diagnosis was calculated for the control arm using a simplified risk score at diagnosis. The full prognostic index discriminates well men with PCa with different survival. The area under the curve (AUC) was 0.83 for both the 3–6 year and 9–15 year validation periods. In the simplified risk score, patients with a low risk score at diagnosis had the most favorable survival, while the outcome was poorest for the patients with high risk scores. The prognostic index was able to distinguish well between men with higher and lower survival, and the simplified risk score can be used as a basis for decision making. [ABSTRACT FROM AUTHOR]

Introduction. The aim of the study was to evaluate the performance of HPV-based screening as compared to conventional cytology in the framework of routine cervical cancer screening. Materials and method. 46,708 women, aged 35-60 years old, participated in the regional cervical cancer screening program of the city of Tampere and its surroundings in 2012-2014. The screening method used in Tampere was Abbot RealTime HPV test with cytology triage, while in the surroundings, conventional cytology was used. All women with LSIL or worse cytology were referred to colposcopy, while women with either borderline cytology or hrHPV+ and normal or borderline cytology were invited to a reflex screening in the following year. All other women were referred to the next screening round after five years. Results. The attendance rate was similar in both goups (72% and 71%). The detection rates of CIN 2+ and 3+ were greater in the HPV than in the PAP group during the index screening years (2012-2014), or 3.2/1000 and 2.3/100 versus 1.9/1000 and 1.1/1000, and in the reflex re-screening years (2013-2015), 4.4/1000 and 2.4/100 versus 1.2/1000 versus 0.6/100, respectively, with the total outcomes of 7.5/1000 and 4.7/1000 versus 3.1/1000 and 1.7/1000, respectively (p<0.0001). Due to a high persistence rate of HPV infection, the total colposcopy rate was higher in the HPV than in the PAP group, or 43.8/1000 and 18.4/1000 (p<0.0001), respectively. Conclusion. Primary hrHPV testing with cytology triage is more sensitive than conventional cytology in the routine screening of precursors for cervical cancer. However, HPV testing is associated with greater colposcopy rate in the reflex screening round. [ABSTRACT FROM AUTHOR]

Background: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) usually presents in middle aged men and shows an indolent clinical behavior. However, up to 30% of the patients present a secondary transformation into aggressive diffuse large B cell lymphoma (DLBCL). The aim of the present study was to characterize morphology and immunophenotype of this kind of DLBCL in detail and compare it with conventional DLBCL.Methods: Morphology and immunophenotype of 33 cases of NLPHL with simultaneous or sequential transformation into DLBCL were investigated. These cases were compared with 41 de novo DLBCL in Finnish men.Results: The majority of cases exhibited different immunophenotypes in the NLPHL and the DLBCL components. The immunophenotype of the DLBCL secondary to NLPHL was heterogeneous. However, BCL6, EMA, CD75 and J-chain were usually expressed in both components (≥73% positive). Overall, the NLPHL component was more frequently positive for EMA, CD75 and J-chain than the DLBCL component. In contrast, B cell markers, CD10 and BCL2, were more frequently expressed and were expressed at higher levels in the DLBCL component than in the NLPHL component. In the independent series of de novo DLBCL 4 cases could be identified with a growth pattern and immunophenotype that suggested that they had arisen secondarily from NLPHL.Conclusions: The morphology and immunophenotype of DLBCL arisen from NLPHL is heterogeneous. Further characterization of the particular molecular features of this subgroup is warranted to be able to better identify these cases among conventional DLBCL. [ABSTRACT FROM AUTHOR]