Inflammatory Atrophy Research Articles

Re: Inflammatory atrophy on prostate needle biopsies: is there topographic relationship to cancer?

INTRODUCTION: Chronic inflammation of longstanding duration has been linked to the development of carcinoma in several organ systems. It is controversial whether there is any relationship of inflammatory atrophy to prostate cancer. It has been suggested that the proliferative epithelium in inflammatory atrophy may progress to high-grade prostatic intraepithelial neoplasia and/or adenocarcinoma. The objective of our study is to compare on needle prostate biopsies of patients showing cancer the topographical relation of inflammatory atrophy and atrophy with no inflammation to adenocarcinoma. MATERIALS AND METHODS: The frequency and extent of the lesions were studied on 172 needle biopsies of patients with prostate cancer. In cores showing both lesions, the foci of atrophy were counted. Clinicopathological features were compared according to presence or absence of inflammation. RESULTS: Considering only cores showing adenocarcinoma, atrophy was seen in 116/172 (67.44%) biopsies; 70/116 (60.34%) biopsies showed atrophy and no inflammation and 46/116 (39.66%) biopsies showed inflammatory atrophy. From a total of 481 cores in 72 biopsies with inflammatory atrophy 184/481 (38.25%) cores showed no atrophy; 166/481 (34.51%) cores showed atrophy and no inflammation; 111/481 (23.08%) cores showed both lesions; and 20/481 (4.16%) showed only inflammatory atrophy. There was no statistically significant difference for the clinicopathological features studied. CONCLUSION: The result of our study seems not to favor the model of prostatic carcinogenesis in which there is a topographical relation of inflammatory atrophy to adenocarcinoma.

Oxidative damage of retinal pigment epithelial cells and age‐related macular degeneration

AbstractDamage to the retinal pigment epithelial (RPE) cells is an early and crucial event in the molecular pathways leading to clinically relevant age‐related macular degeneration (AMD) changes. Oxidative stress, the major environmental risk factor for atrophic AMD, causes RPE injury that results in a chronic inflammatory response, drusen formation, and RPE atrophy. RPE degeneration ultimately leads to a progressive irreversible degeneration of photoreceptors. In vitro studies show that oxidant‐treated RPE cells undergo apoptosis, a possible mechanism by which RPE cells are lost during the early phase of atrophic AMD. The main target of oxidative injury appears to be mitochondria, an organelle known to accumulate genomic damage during aging. Addition of GSH, the most abundant intracellular thiol antioxidant, protects RPE cells from oxidant‐induced apoptosis. Similar protection occurs with dietary enzyme inducers that increase GSH synthesis. In addition, enhancing survival signaling preserves RPE cells under oxidative stress. These results indicate that therapeutic or nutritional intervention to enhance the antioxidant capacity and survival signaling of RPE may provide an effective way to prevent or treat AMD. This review describes major molecular and cellular events leading to RPE death, and presents currently used and new experimental, forthcoming therapeutic strategies. Drug Dev Res 68:213–225, 2007. © 2007 Wiley‐Liss, Inc.

The role of inflammation and infection in the pathogenesis of prostate carcinoma

Prostatitis and prostate carcinoma are both frequent entities of prostatic diseases. Epidemiological studies show significant associations between infection and inflammation and prostatic carcinoma. However, because of various confounding factors the results of these studies are inconclusive. Further findings are therefore needed to confirm the hypothesis that prostatic infection and inflammation might be a cause of prostatic carcinoma. We reviewed selected reports on the role of inflammation and infection in the pathogenesis of prostate carcinoma. Extensive genetic analyses show that several gene products, e.g. 2'-5'-oligoadenylate (2-5 A)-dependent Rnase, macrophage scavenger receptor 1 and Toll-like receptor-4, influence the susceptibility of prostate cells to infectious agents. Proliferative inflammatory atrophy (PIA) could be a connection between prostatitis and prostatic carcinoma. In the transition from PIA to prostatic intraepithelial neoplasia, the function of cellular detoxification is gradually lost by silencing of glutathione-S transferase, a detoxifying enzyme. This cellular feature leads to an increased susceptibility of the prostatic epithelial cells to genomic damage by inflammatory oxidants or nutritional carcinogens. Consecutive somatic genome damage might then arise which modulates the further pathogenesis of prostate carcinoma. Summarising these epidemiological, genetic and cell biological aspects, infectious prostatitis might have a causative role in the complex and multifactorial process of prostate carcinogenesis.

Increased expression of CCAAT/enhancer‐binding protein beta in proliferative inflammatory atrophy of the prostate: Relation with the expression of COX‐2, the androgen receptor, and presence of focal chronic inflammation

Proliferative inflammatory atrophy (PIA) in the prostate has been proposed to be a precursor to prostate cancer. CCAAT/enhancer-binding protein beta (C/EBPbeta) is an important transcription factor involved in cellular proliferation and differentiation. Activation of C/EBPbeta plays a crucial role during the initial stage of cyclo-oxygenase 2 (COX-2) induction by proinflammatory mediators. Overexpression of C/EBPbeta has been reported in several human tumors. Nevertheless, the C/EBPbeta expression and functions in human prostate tissue are basically unknown. C/EBPbeta immunohistochemical staining was performed on 45 benign prostate hyperplasia (BPH) samples. The expression of C/EBPbeta in PIA lesions and normal-appearing acini was analyzed. In addition, by using double-IHC staining, C/EBPbeta expression and the association with chronic inflammatory cell density, co-expression of COX-2 and androgen receptor (AR) were also investigated. C/EBPbeta was occasionally observed in normal-appearing prostate acini (4.9% +/- 6.7%, Mean +/- SD) but was clearly overexpressed in PIA lesions (81.8% +/- 16.4%) (P < 0.0001). Atrophic glands with T-lymphocyte and macrophage inflammation expressed higher level of C/EBPbeta. Furthermore, C/EBPbeta correlated significantly with COX-2 expression. Downregulation of the AR was common in PIA and was also related to the C/EBPbeta overexpression. The data demonstrated that chronic inflammation appeared to play roles in the induction of C/EBPbeta expression in prostate epithelium, which was in turn associated with increased COX-2 expression and AR downregulation. In combining with other molecular alteration in the epithelium of PIA, it is suggested that these cells might be a kind of intermediate cells and involved in the pathogenesis of prostate cancer.

Inflammatory atrophy on prostate needle biopsies: is there topographic relationship to cancer?

Chronic inflammation of longstanding duration has been linked to the development of carcinoma in several organ systems. It is controversial whether there is any relationship of inflammatory atrophy to prostate cancer. It has been suggested that the proliferative epithelium in inflammatory atrophy may progress to high-grade prostatic intraepithelial neoplasia and/or adenocarcinoma. The objective of our study is to compare on needle prostate biopsies of patients showing cancer the topographical relation of inflammatory atrophy and atrophy with no inflammation to adenocarcinoma. The frequency and extent of the lesions were studied on 172 needle biopsies of patients with prostate cancer. In cores showing both lesions, the foci of atrophy were counted. Clinicopathological features were compared according to presence or absence of inflammation. Considering only cores showing adenocarcinoma, atrophy was seen in 116/172 (67.44%) biopsies; 70/116 (60.34%) biopsies showed atrophy and no inflammation and 46/116 (39.66%) biopsies showed inflammatory atrophy. From a total of 481 cores in 72 biopsies with inflammatory atrophy 184/481 (38.25%) cores showed no atrophy; 166/481 (34.51%) cores showed atrophy and no inflammation; 111/481 (23.08%) cores showed both lesions; and 20/481 (4.16%) showed only inflammatory atrophy. There was no statistically significant difference for the clinicopathological features studied. The result of our study seems not to favor the model of prostatic carcinogenesis in which there is a topographical relation of inflammatory atrophy to adenocarcinoma.

TMPRSS2-ERG Fusion Prostate Cancer: An Early Molecular Event Associated With Invasion

Prostate cancer (PCA) is one of the most prevalent cancers and a major leading cause of morbidity and mortality in the Western world. The TMPRSS2-ERG fusion was recently identified as a common recurrent chromosomal aberration in this malignancy. In our study, we interrogated a broad spectrum of benign, precursor, and malignant prostatic lesions to assess the TMPRSS2-ERG fusion status using a multicolor interphase fluorescence in situ hybridization assay. Samples from hospital-based cohorts consisted of 237 clinically localized PCA, 34 hormone naive metastases, 9 hormone refractory metastases, 26 high grade prostatic intraepithelial neoplasia lesions, 15 samples of benign prostatic hyperplasia, 38 of proliferative inflammatory atrophy, and 47 of benign prostatic tissue. The TMPRSS2-ERG fusion was present in 48.5% of clinically localized PCA, 30% of hormone naive metastases, 33% of hormone refractory metastases, and in 19% of high grade prostatic intraepithelial neoplasia lesions in intermingling to cancer foci. Almost all these fusion positive cases show a homogenous distribution of the fusion pattern. In contrast, none of the other samples harbored this genetic aberration. If we consider the high incidence of PCA and the high frequency of this gene fusion, TMPRSS2-ERG is the most common genetic aberration so far described in human malignancies. Furthermore, its clinical application as a biomarker and ancillary diagnostic test is promising given its high specificity.

Commentary II

Although the main criterion for disease progression in multiple sclerosis (MS) remains the clinical evaluation of the patient, recent changes in CNS MRI techniques have also been of value in determining the evolution of the disease. Important insights into inflammatory changes, tissue loss, and atrophy have been obtained with MRI, enabling these additional parameters to be used as measures of disease progression and treatment efficacy. Much effort has been made in several disease states, including MS, to show that particular drugs have the capacity for neuroprotection, that is, the ability to salvage, preserve, or regenerate cells and maintain the integrity and function of the nervous system. Neuroprotection has been difficult to prove in humans, since drugs that reduce the inflammatory phase of MS may limit tissue destruction and allow better healing without actually inducing cell regeneration. Neuroprotection in MS must address the multiple pathologies that contribute to the disease, including the acute inflammatory injury to myelin and axons, the pathophysiologic factors that mediate myelination and remyelination, and protection against death of oligodendrocytes and neurons. Furthermore, the recently recognized protective benefit of immunologic activity, i.e., the ability of immune cells to promote growth, survival, and plasticity of nerve tissue, must be considered with any disease intervention that modulates the immune system. As a result, there are continuing efforts to establish a balance between effective immune system modulation and suppression in order to enable optimal disease control and to balance risks and benefits. In the second half of this supplement, the articles by Hohlfeld et al.,1 Khan,2 Zivadinov,3 and Arnold,4 focus on the difficulties in practice of assessing neuron structural integrity: the newly discovered and …

Prostate cancer prevention

Prostate cancer, a common cause of morbidity and mortality in the developed world, ought to be a preventable disease. This review focuses on prostate cancer prevention in the context of new mechanistic insights into human prostatic carcinogenesis. Evidence is accumulating to implicate infection and inflammation as contributors to prostate cancer development. Inherited prostate cancer susceptibility genes discovered thus far encode participants in host responses to infection. Proliferative inflammatory atrophy, a prostate cancer precursor lesion, ties inflammatory responses to prostatic carcinogenesis. Somatic epigenetic alterations, present in all prostate cancers, appear to arise in the setting of inflammation. Finally, a newly identified somatic genome change, involving a fusion between an androgen-regulated gene, TMPRSS2, and genes encoding members of the ETS family of transcription factors, may provide a clue as to why prostate cancer cells exhibit androgen dependence for growth and survival. The contributions of infection and inflammation to the early development of prostate cancer suggest prevention strategies featuring prevention or eradication of infection, amelioration of inflammation, or attenuation of genome-damaging reactive oxygen and nitrogen species. The acquisition of androgen dependence later during prostate cancer pathogenesis suggests the use of approaches targeting androgen signaling, including inhibitors of 5alpha-reductase.

Development of an in vivo mouse model to study oral submucous fibrosis

Epidemiological data have shown an association of areca nut chewing with oral submucous fibrosis (OSF). Experimental evidence to confirm this has been limited. Fibrosis-promoting activity of areca nut was tested in an animal model. Buccal mucosa of a group of 20 female BALB/c strain mice, 10-12 weeks of age, was treated twice daily 6 days per week with topical application of aqueous areca nut extracts for 300-600 days. A control group (n = 20) was treated with 50 mM NaCl. The influence of areca nut on the oral epithelium and connective tissue was recorded semiquantitatively by light microscopy. The areca nut-treated oral epithelium showed progressive changes in epithelial thickness leading to atrophy, increased cellularity of fibroblasts, fibrosis of connective tissue, focal infiltration of inflammatory cells and muscle atrophy. On killing after 600 days of treatment, the scores on cellularity, inflammation and muscle atrophy were significantly different to the control group (P = 0.03). The study provides further evidence that areca nut contributes to the development of OSF in treated animals. The model has the potential to test synergism of areca nut with other carcinogens and any therapeutic interventions.

Use of Fujinon FICE and High Resolution Magnification Endoscopy to Identify Chemical Gastritis Vs. Helicobacter Pylori Related Gastritis

Background: The Fujinon Company has recently added FICE (Fujinon Intelligent Color Enhancement), to the new processor EPX-4400. This technology allows the combination of spectral images generated from a color image decomposed according to specific wavelengths. The system presets 10 different options that can be freely changed. The combination of FICE with high resolution-magnification in the Fujinon EG 590 ZW gastroscope gives a potential advantage in the evaluation by electronic chromoendoscopy of the characteristics of the gastrointestinal mucosa. Aim: To determine the presence of specific endoscopic patterns for normal mucosa, mucosa with inflammation and the patterns that suggests the presence or absence of Helicobacter pylori (Hp). Methods: This study includes 251 patients who underwent Upper GI endoscopy for dyspeptic symptoms. The results were classified in 3 different patterns: (1) Increased superficial vascular pattern, discrete separation of crypts, “empty” aspect of the crypts (pinhole or “halo” aspect) viewed with FICE (set 4 and 6). (2) Decreased superficial vascular pattern, “filled” aspect of the crypts plus enlargement and increased opacity viewed with FICE (set 4 and 6). (3) Indeterminate pattern were crypt arrangement is irregular and discrete segmentation of mucosa with or without vascular superficial pattern present. Biopsies were taken in all patients for HPFAST and 20% of the cases were correlated with histopathological analysis. The endoscopy was performed with Fujinon gastroscope EG-590 ZW5. The pathologist was not aware of the type of pattern observed on each patient. Results: 251 patients were enrolled (136 males, mean age 49.9, median 51). Hp was present in 93 patients (37.1%). In 132 patients a type 1 pattern was identified, 9% of these patients were Hp. In 87 patients type 2 pattern was recognized, 81% Hp. Thirty-two patients had type 3 pattern, 31% Hp positive. The correlation of histological findings revealed chemical gastropathy as a common finding in type 1 pattern and chronic active gastritis in most patients with type 2 pattern. The type 3 pattern patients had marked inflammatory process and atrophy in some cases. The FICE system was efficient for the easy recognition of the patterns. The most representative observation was performed at the gastric body. Conclusion: Fujinon FICE technology associated with high-resolution magnification endoscopy can help identify mucosal patterns and predict the presence of Hp. This system helps choosing the most representative place to biopsy. Further studies will help clarify the relevance of the details observed in the presence or absence of Hp.

Inflammation in prostate carcinogenesis

About 20% of all human cancers are caused by chronic infection or chronic inflammatory states. Recently, a new hypothesis has been proposed for prostate carcinogenesis. It proposes that exposure to environmental factors such as infectious agents and dietary carcinogens, and hormonal imbalances lead to injury of the prostate and to the development of chronic inflammation and regenerative 'risk factor' lesions, referred to as proliferative inflammatory atrophy (PIA). By developing new experimental animal models coupled with classical epidemiological studies, genetic epidemiological studies and molecular pathological approaches, we should be able to determine whether prostate cancer is driven by inflammation, and if so, to develop new strategies to prevent the disease.

The Fully Human Antibody CNTO1275 Effectively Inhibits Human IL-12 and IL-23 Mediated Th1 and Th17 Cell Function and Provides Clinical Benefit to Patients with Plaque Psoriasis

Whether atrophy is a precursor to high-grade prostatic intraepithelial neoplasia (HGPIN) and cancer is controversial. A virtual slide set comprising 48 prostatectomy cases was used to investigate associations among the amounts and spacing of these entities. Foci of atrophy without inflammation (A), atrophy with inflammation (AI), cancer (by patterns), and HGPIN were digitally annotated. Atrophy’s proximity to cancer and HGPIN was assessed with two measurements: abutment (touching) or nearness (≤2 μm without touching). Area sums per specimen were computed for A, AI, cancer, and HGPIN. Abutment rates of AI and A foci to cancer were 23% versus 21% (p = NS); for nearness, 29% of AI foci were near to cancer versus 12% of A (P = .0001). Abutment or nearness of A and AI to HGPIN were in the 1.4% to 2.4% range. When A, AI, or HGPIN abutted cancer, it was disproportionately to Gleason grade 3 cancer foci even after adjusting for the lesser frequency of higher-grade cancer foci. Area sums of A, AI, or (A + AI) per specimen showed no correlations with those of HGPIN, and mostly negative ones with area sum and with tumor volume of cancer. In conclusion, atrophy with inflammation showed some preferential spatial association to cancer, although area sums of atrophy with or without inflammation correlated negatively with those of cancer. These divergent spatial associations suggest that atrophy and inflammation in biopsy specimens may have clinical relevance. The frequency of inflammatory atrophy (AI) merging with HGPIN was far less than reported previously, weakening the theory that AI gives rise to HGPIN.

Quantitative immunohistochemical detection of the molecular expression patterns in proliferative inflammatory atrophy

The proliferative inflammatory atrophy (PIA) is considered as a possible precursor of prostate intraepithelial neoplasia (PIN) or prostate cancer (PCa). In this study we assessed quantitatively the expression of AMACR, p63, COX-2, GST and iNOS in serial paraffin-embedded tissue sections obtained after radical prostatectomy of PCa patients (n = 30). The applicability of these markers to distinguish PIA, PIN and PCa was evaluated. We also compared the immunohistochemical expression profiles of AMACR, COX-2 and GST in the luminal and basal cells in lesions of PIN arisen in PIA or PIA alone. Two different patterns of COX-2 expression according to the p63 status of the basal cells were found. This observation gives us grounds to hypothesize that the diverse COX-2 patterns resulted from an initial basal cell damage which subsequently propagated to its luminal secretory cells progeny.

Overexpression of Redox-Active Protein Thioredoxin-1 Prevents Development of Chronic Pancreatitis in Mice

Chronic pancreatitis (CP) is considered to result from repetitive pancreatic injury, and sustained production of various proinflammatory cytokines and chemokines are closely involved in its pathogenesis. Monocyte chemoattractant protein 1 (MCP-1), a member of the CC chemokine family, is believed to contribute to the progression of CP through monocyte/macrophage recruitment. This study aimed to clarify the protective role of thioredoxin-1 (TRX-1), a redox-regulating protein with antioxidative activity, in MCP-1 production and pancreatic fibrosis using a CP model in transgenic mice overexpressing TRX-1 (TRX-1-TG mice) and wildtype C57BL/6 mice. Experimental CP was induced by repeated administration of cerulein and lipopolysaccharide for 6 weeks. In TRX-1-TG mice, pancreatic atrophy was ameliorated, and histologically detectable inflammatory cell infiltration, glandular atrophy, and pseudotubular complex formation were suppressed. Overexpression of TRX-1 also attenuated pancreatic fibrosis and suppressed the activation of pancreatic stellate cells. Serum levels of MCP-1 and pancreatic expression of transforming growth factor-beta, platelet-derived growth factor, and MCP-1 were reduced in TRX-1-TG mice compared with levels in wild-type mice. Overexpression of TRX-1 also reduced H(2)O(2)-induced MCP-1 production in isolated pancreatic acinar cells. These results indicate that TRX-1 can potentially attenuate pancreatic fibrosis via the suppression of oxidative stress and MCP-1-mediated chronic inflammation.

The Influence of Chronic Inflammation in Prostatic Carcinogenesis: A 5-Year Followup Study

We investigated an association between chronic prostatic inflammation and prostate carcinogenesis. Initial prostate needle biopsies from 177 patients with clinical parameters suspicious for malignancy were examined. We evaluated them for the presence and extent of chronic inflammation and other pathological findings. Findings in followup biopsies during the next 5 years were reviewed and correlated with the initial results. Two patients subset were identified, including 144 patients with and 33 without chronic inflammation in the initial biopsies. Additional pathological findings in some cases in each group included simple atrophy, high grade prostatic intraepithelial neoplasia, adenocarcinoma and atypical small acinar proliferation. Post-atrophic hyperplasia and proliferative inflammatory atrophy were noted only in patients with chronic inflammation. A significant association between serum prostate specific antigen and the degree of inflammation was observed in needle biopsies. In repeat biopsies within 5 years in patients with chronic inflammation 29 new cancers were diagnosed, representing a new cancer incidence of 20%. Of these cancers 6 occurred in patients in whom initial biopsies showed only chronic inflammation, 15 occurred in patients with initial post-atrophic hyperplasia/proliferative inflammatory atrophy lesions, 7 occurred in patients with initial high grade prostatic intraepithelial neoplasia and chronic inflammation, and 1 occurred in a patient with initial atypical small acinar proliferation and chronic inflammation. High grade prostatic intraepithelial neoplasia was newly discovered in 9 patients in the initial chronic inflammation group, of whom 7 had post-atrophic hyperplasia/proliferative inflammatory atrophy and 2 had simple atrophy and chronic inflammation in the initial biopsies. In contrast, in 33 patients initially showing no inflammation adenocarcinoma was subsequently found in 2 (6%). One of these patients had high grade prostatic intraepithelial neoplasia and the other had atypical small acinar proliferation on initial biopsies. Chronic inflammation may be a significant risk factor for prostatic adenocarcinoma.

Different Types of Atrophy in the Prostate With and Without Adenocarcinoma

ObjectivesThe purpose of this study was to evaluate, according to a classification proposed by a working group, the extent and type of atrophy lesions in radical prostatectomy specimens obtained from patients with prostatic carcinoma and benign prostatic hyperplasia (BPH), and to compare the prevalence and types of atrophy between two investigated groups. MethodsHistologic analysis of 1096 slides from 50 patients with carcinoma and 277 slides from 31 patients with BPH was performed to evaluate, according to the new prostatic atrophy classification, the number of foci and type of atrophic lesions. ResultsAge, Gleason grade, and TNM showed no significant correlation with the number of proliferative atrophy (PA) and proliferative inflammatory atrophy (PIA) foci (p>0.05). PIA was significantly more frequent in prostates with carcinoma (1.63 vs 1.27 atrophic lesions per slide) (p<0.001), whereas PA displayed an increased frequency in BPH (2.28 vs 0.76 atrophic lesions per slide) (p<0.001). ConclusionsWe confirmed that PA and PIA are common findings in prostates with and without carcinoma, but the question of whether inflammation produces tissue damage and PA or whether some other insult induces the tissue damage and atrophy directly, with inflammation occurring secondarily, is still unresolved.

Cyclooxygenase-2 Selective Inhibitors and Prostate Cancer: What Is the Clinical Benefit?

Cyclooxygenase-2 Selective Inhibitors and Prostate Cancer: What Is the Clinical Benefit?

1496: Inflammatory Atrophy in Prostate Needle Biopsies: Relationship to Cancer?

You have accessJournal of UrologyDiscussed Poster, Wednesday, May 24, 2006, 9:00 am - 12:00 pm1 Apr 20061496: Inflammatory Atrophy in Prostate Needle Biopsies: Relationship to Cancer? Ubirajara Ferreira, Athanase Billis, Leandro L. Freitas, Luiz A. Magna, Renato N. Pedro, Wagner E. Matheus, and Nelson R. Netto Ubirajara FerreiraUbirajara Ferreira More articles by this author , Athanase BillisAthanase Billis More articles by this author , Leandro L. FreitasLeandro L. Freitas More articles by this author , Luiz A. MagnaLuiz A. Magna More articles by this author , Renato N. PedroRenato N. Pedro More articles by this author , Wagner E. MatheusWagner E. Matheus More articles by this author , and Nelson R. NettoNelson R. Netto More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)33700-5AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "1496: Inflammatory Atrophy in Prostate Needle Biopsies: Relationship to Cancer?." The Journal of Urology, 175(4S), p. 483 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 175Issue 4SApril 2006Page: 483 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Ubirajara Ferreira More articles by this author Athanase Billis More articles by this author Leandro L. Freitas More articles by this author Luiz A. Magna More articles by this author Renato N. Pedro More articles by this author Wagner E. Matheus More articles by this author Nelson R. Netto More articles by this author Expand All Advertisement PDF DownloadLoading ...

1497: Predictive Value of Proliferative Inflammatory Atrophy (PIA) for Prostate Cancer on Repeat Prostate Biopsy

1497: Predictive Value of Proliferative Inflammatory Atrophy (PIA) for Prostate Cancer on Repeat Prostate Biopsy

P16 Is upregulated in proliferative inflammatory atrophy of the prostate

Proliferative inflammatory atrophy (PIA) of the prostate is a common histological finding that has been postulated to be associated with prostate cancer. We examine PIA lesions for the expression of p16/CDKN2, a cyclin-dependent kinase inhibitor frequently altered in prostate cancer. Within tissues from two independent patient populations ("Test Set" and "Validation Set") undergoing radical prostatectomy, PIA lesions were identified and subjected to immunohistochemical staining for p16. Atrophic epithelial cells and regional normal epithelium were scored for the extent of p16 staining. In the Test Set, staining was also performed for the proliferation marker Ki-67. Double label immunofluorescence was employed to co-localize staining for p16 and Ki-67. p16 expression was elevated in PIA in both data sets compared to normal epithelium (mean percent of cells staining positive in PIA = 11.1%-16.2%; mean percent of cells staining positive in normal = 0.6%-1.3%) (P = 0.0001). As expected from prior studies, the mean Ki-67 index was higher in PIA lesions (mean 8.2% staining positive) versus normal epithelium (mean 1.9% staining positive) (P = 0.0001), and the extent of staining for p16 correlated with Ki-67 (r = 0.7, P < 0.0001). However, co-localization immunofluorescent studies did not demonstrate staining for nuclear p16 and Ki-67 in the same cells. Increased p16 expression accompanies increased cell proliferation in PIA lesions of the prostate. Yet, on the individual cell level, the upregulation of p16 in PIA lesions appears to represent a non-proliferative stress response, possibly to oxidative damage.