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Clinical significance of proliferative inflammatory atrophy finding in prostatic biopsies

Proliferative inflammatory atrophy (PIA) has been involved in prostatic carcinogenesis. However, little is known about the clinical significance of a PIA finding in prostatic biopsies (PBs). The aim of this study is to determine the incidence of prostate inflammatory atrophy (PIA) in prostate biopsies (PBs), its association to high‐grade prostatic intraepithelial neoplasia (HGPIN), prostate cancer (PCa), and tumor aggressiveness.

Significado clínico de la atrofia proliferativa inflamatoria en la biopsia prostática

INTRODUCTION Proliferative inflammatory atrophy (PIA) is a frequently observed lesion in prostate biopsies and some authors have postulated its involvement in prostate carcinogenesis. However, the mechanisms that would permit its neoplastic transformation and the clinical significance of its finding in a prostate biopsy is currently not well known. OBJECTIVE To analyze the characteristics of the PIA lesion, its possible role in prostate carcinogenesis and its relation with the tumor aggressiveness. MATERIAL AND METHOD A systematic review was made of the literature in PubMed with the terms «proliferative inflammatory atrophy» or «PIA» and «prostate.» The most important findings are summarized in accordance with the study objective. RESULTS PIA seems to be involved in prostate carcinogenesis. This hypothesis is based on its frequent association to cancer lesions (CaP) and on some genetic alterations that are common to the high grade prostatic intraepithelial neoplasia (HGPIN) and to the CaP, fundamentally deficit in GSTP1 expression and overexpression of AGR2. Currently, there are no epidemiological studies that evaluate the incidence of PIA or its association with HGPIN and CaP. Only one study, carried out by our group, has determined the global incidence of PIA in 30% of the prostate biopsies, a lower association to CaP than the HGPIN lesion and an association between PIA and tumors of lower and insignificant grade. CONCLUSIONS PIA shares genetic alterations with HGPIN and CaP. Currently, there is no epidemiologic evidence to consider that the PIA is associated to a greater incidence of CaP and the genetic and epidemiological data available suggest its association to not very aggressive tumors.

Clinical Significance of Proliferative Inflammatory Atrophy in Negative Prostatic Biopsies: Pia in Negative Prostatic Biopsies

To analyze the association between prostatic proliferative inflammatory atrophy finding in negative prostate biopsies and future detection of prostate cancer (PCa) and its aggressiveness in men subjected to repeat biopsies, due to persistent suspicion of PCa.

MP85-16 STUDY OF ALTERED RATIOS OF PROTEIN KINASE CK2 CATALYTIC SUBUNITS AND REGULATORY SUBUNIT (CK2BETA) IN RENAL CELL CARCINOMA. RELATION WITH EPITELIAL-TO-MESENCHYMAL TRANSITION MARKERS (IL-6/STAT3)

INTRODUCTION AND OBJECTIVES: Epitelial-to-mesenchymal transition (EMT) is a well characterised process linked to tumour progression and metastasis in a number of carcinomas. EMT enables carcinoma cells to lose cell to cell contacts and endows them with stem cell-like properties to invade and initiate metastasis. Recent reports have identified EMT as potentially playing a significant role in RCC disease recurrence, invasion and metastasis. Several signalling pathways like HIF/2 and IL-6/STAT, are well known inducers of the EMT phenotype. Protein kinase CK2 is a constitutively active serine/threonine kinase consisting of two catalytic subunits (CK2alpha/alpha’) and two regulatory subunits (CK2Beta) and is present in the nucleus and cytoplasm of all eukaryotic cells. The imbalance of CK2 catalytic and regularory subunits, due to underexpression of CK2Beta subunit, has been correlated with the expression of EMT markers. In clear cell renal cell carcinoma (ccRCC), the alterations in the ratios between CK2 subunits during the neoplasic process seems to participate at different stages of tumour progression METHODS: We analyzed the expression and distribution of CK2 subunits in samples of clear cell renal carcinomas (ccRCC) and renal healthy tissue from the same patients by immunohistochemistry on TMAs and Western-blot in a total of 98 patients. Tumour registry data and patient outcome were retrospectivelly collected and correlates with clinicopathological data (F€ urhman grade, pT stage and Risk group) and with IL-6/STAT inmunoexpression RESULTS: We observed an increase of CK2 in tumors. Regarding the subcellular distribution in normal tissue CK2alpha is predominantly cytoplasmic whereas tumors markedly increased in the core, with only a slight decrease in the cytoplasm, indicating nuclear overexpression CK2alpha tumors. CK2Beta changes are more discreet and its nuclear accumulation in tumors could be due to translocation from the cytoplasm, which is a marked decrease. Using 786-O cells, derived ccRCC pVHL deficient, and 786-O cells stably transfected with an expression vector pVHL, we have observed that the presence of VHL not decrease but it increases CK2alpha levels by altering the ratio between CK2alpha/CK2Beta. It was observed higher survival in the subset patients with underexpression of CK2sBeta although log-rank was not significant (0,301). The combination of overexpression of STAT3 and underexpression ok CK2Beta seems to provide a higher survival hazard ratio of 4,252 (95% IC, 1,182-18.413) CONCLUSIONS: The results indicate CK2alpha overexpression in clear cell renal cell carcinoma by a mechanism that does not appear due to inactivation of VHL. In patients with underexpression of IL-6/STAT3, CK2Beta was no able to discriminate any behaviour, but the patients defined as poor prognostic when STAT3 was overexpressed has similar survival than those that had underexpression of STAT3. The combination of overexpression of STAT3 and underexpression of CK2Beta provided a higher survival rate

MP54-09 MANAGEMENT OF SMALL RENAL MASSES USING CONTRAST-ENHANCED ULTRA SOUND PERCUTANEOUS RADIOFREQUENCY ABLATION: FUNCTIONAL RESULTS, EARLY ONCOLOGICAL OUTCOMES AND COMPLICATIONS ACCORDING THE R.E.N.A.L NEPHROMETRY SCORE

underwent PN, in 33.3% of which a MIT was adopted. Majority of RNs for T1 tumours were performed using a MIT (90.3%). Of the laparoscopic PNs, 30.5% were robot-assisted. No significant difference in intra operative complications was found between the RN and PN groups (4% vs 4.3% respectively; p1⁄40.79). However PN accounted for a higher postoperative complications rate (RN 11.3% vs PN 17.6%; p1⁄40.0002). Operative time between RN and PN was comparable (141min vs 145min; p1⁄40.25). Blood loss was less in the RN group (mean for RN 165mL vs PN 323mL; p<0.0001), however, transfusion rates were similar (3.2% vs 2.6% respectively; p1⁄40.47). RN was associated with a shorter length of stay (median 4 days vs 5 days; p1⁄40.0004). Comparison between robot-assisted and laparoscopic PN showed no significant differences in operation time, blood loss, warm-ischaemia time or complications. CONCLUSIONS: PN was the modality of choice for treatment of T1a tumours whereas RN was preferred for T1b tumours. MIT have been widely adopted for RN but not for PN. The age and WHO performance status would have influenced decision making. Despite the advances in surgical technique, a substantial risk of postoperative complications remains with PN.

MP41-07 PROLIFERATIVE INFLAMMATORY ATROPHY IS ASSOCIATED TO LESS AGGRESSIVE AND INSIGNIFICANT TUMORS IN RADICAL PROSTATECTOMY SPECIMENS

INTRODUCTION AND OBJECTIVES: Proliferative inflammatory atrophy (PIA) has been proposed to be involved in prostate carcinogenesis by suggesting that it may rise to prostatic carcinoma (PCa) either directly or indirectly by first developing into high grade prostatic intraepithelial neoplasm (HGPIN). We have studied the PIA genetic signature 2 and more recently we have learned that PIA incidence in prostatic biopsies is around 30%, and it is associated to lower PCa detection and less aggressive tumors . The objectives of this study were to assess the incidence of PIA lesion in radical prostatectomy (RP) specimens and to confirm the hypothesis that PIA is associated to less aggressive tumors. METHODS: A retrospective study conducted in 200 consecutive patients subjected to RP was done. A single pathologist identified PIA in all specimens and this finding was related with: age, serum PSA, prostate volume, Gleason score, pathologic stage, percentage of tumor in the gland, maximal length of index tumor, perineural invasion, multifocality, bilaterality, insignificant cancer, positive margins, and HGPIN. Mann-Witney U test and Chi-square Pearson test were used to compare data. RESULTS: PIA was present in 64 specimens (32%). Age, serum PSA and prostate volume were similar in patients with and without PIA. Respectively, high Gleason grade was present in 34.4% and 49.3%, p1⁄40.033; non-organ confine disease in 10.9% and 16.9%, p1⁄40.187; perineural invasion in 59.4 and 74.3%, p1⁄40.025; multifocal tumors in 59.4% and 74.3%, p1⁄40.001; bilateral tumors in 46.9% and 70.5%, p1⁄40.005; insignificant tumors in 17.2% and 6.6%, p1⁄40.022; HGPIN in 92.2% and 90.4%, p1⁄40.456. CONCLUSIONS: This study confirms that the incidence of PIA in RP specimens was similar to the one observed previously in prostatic biopsies (32% versus 30%). PIA was not associated to HGPIN. PIA was associated to many pathologic characteristics of less aggressive tumors. Of great clinical interest could be the finding that PIA is associated to unilaterial, unifocal, low grade, and insignificant tumors. 1 De Marzo et al. Am J Pathol 1999; 155: 1985-92. 2 Morote et al. Annual EAU Congress 2012; P-848. 3 Morote el al. Annual AUA Meeting 2013; P-2226.