Dipeptidyl peptidase 9 (DPP9) in human skin cells.

BACKGROUND: Dipeptidyl peptidase 9 (DPP9) is a relatively new member of the DPPIV family of prolyl dipeptidases which is ubiquitously expressed. Its role in regulation of immune responses and proliferation of epithelial carcinoma cells was reported. There is no data on possible role of DPP9 expressed in skin epithelial cells (keratinocytes) and in dermal fibroblasts. MATERIALS AND METHODS: Transcriptional and protein expression of DPP9 and DPPIV was examined in fibroblasts and keratinocytes isolated from normal human skin. Localization of DPP9 and its sub-localization in Golgi were determined by immunocytochemistry staining. DPPIV-like enzyme activity was determined in cell lysates and in isolated cell fractions containing membranes (M), cytosol (C) and content of organelles/endosomes/vesicles (V). Relative contribution of DPPIV and DPP8/9 enzyme activity in these fractions was determined by using selective inhibitors: sitagliptin (selective for DPPIV) and 1G244 (selective for DPP9 and a highly homologous DPP8). Possible roles of DPP8/9 via its enzyme activity were analysed by assessment of survival and proliferative capacity of fibroblasts and HaCaT cells of keratinocyte origin in the presence of the inhibitors. Possible role of DPP9 in cell migration and/or adhesion was analysed in fibroblasts and HaCaT cells after DPP9 gene silencing. RESULTS: Fibroblasts and keratinocytes exerted comparable level of DPP9 both at transcriptional and protein level. Fibroblasts strongly expressed DPPIV, whereas in keratinocytes DPPIV expression was low. DPP9 expression was found in cytosol and in perinuclear area of some fibroblasts, or in scattered pattern of keratinocytes, as well as in nuclei of some cells. Only low level of DPP9 sub-localization within Golgi was observed in fibroblasts and keratinocytes. DPPIV-like enzyme activity was about 5 times higher in lysates of fibroblasts than of HaCaT cells. In fibroblasts DPPIV-like enzyme activity was mainly (65%) found in the fraction containing cell membranes (M) and was predominantly (86.9%) due to DPPIV. In contrast, in HaCaT cells the DPPIV-like enzyme activity was mainly (84.2%) found in cytosol (C) and was predominantly (95.6%) due to DPP8/9. Survival and the proliferative capacity were significantly diminished in the presence of 10µM 1G244, both in fibroblasts and in HaCaT cells, suggesting possible role of DPP8/9 enzyme activity in regulation of survival and proliferation of these cells. DPP9 gene silencing resulted in decreased adhesion of fibroblasts, as well as in decreased migration of fibroblasts and HaCaT cells. Accumulation of DPP9 on the edges of plasma membranes of fibroblasts and keratinocytes adhering to surface supports the idea of possible role of DPP9 in cell adhesion. CONCLUSIONS: This is the first study showing protein expression, sub-localization and possible biological roles of DPP9 expressed in isolated human skin cells. The data may be relevant for development of new drugs against skin diseases by targeting DPP9 expressed in the skin cells.

Distribution of organic anion transporters NaDC3 and OAT1-3 along the human nephron.

The initial step in renal secretion of organic anions (OAs) is mediated by transporters in the basolateral membrane (BLM). Contributors to this process are primary active Na(+)-K(+)-ATPase (EC 3.6.3.9), secondary active Na(+)-dicarboxylate cotransporter 3 (NaDC3/SLC13A3), and tertiary active OA transporters (OATs) OAT1/SLC22A6, OAT2/SLC22A7, and OAT3/SLC22A8. In human kidneys, we analyzed the localization of these transporters by immunochemical methods in tissue cryosections and isolated membranes. The specificity of antibodies was validated with human embryonic kidney-293 cells stably transfected with functional OATs. Na(+)-K(+)-ATPase was immunolocalized to the BLM along the entire human nephron. NaDC3-related immunostaining was detected in the BLM of proximal tubules and in the BLM and/or luminal membrane of principal cells in connecting segments and collecting ducts. The thin and thick ascending limbs, macula densa, and distal tubules exhibited no reactivity with the anti-NaDC3 antibody. OAT1-OAT3-related immunostaining in human kidneys was detected only in the BLM of cortical proximal tubules; all three OATs were stained more intensely in S1/S2 segments compared with S3 segment in medullary rays, whereas the S3 segment in the outer stripe remained unstained. Expression of NaDC3, OAT1, OAT2, and OAT3 proteins exhibited considerable interindividual variability in both male and female kidneys, and sex differences in their expression could not be detected. Our experiments provide a side-by-side comparison of basolateral transporters cooperating in renal OA secretion in the human kidney.

Localizations of Na(+)-D-glucose cotransporters SGLT1 and SGLT2 in human kidney and of SGLT1 in human small intestine, liver, lung, and heart.

Novel affinity-purified antibodies against human SGLT1 (hSGLT1) and SGLT2 (hSGLT2) were used to localize hSGLT2 in human kidney and hSGLT1 in human kidney, small intestine, liver, lung, and heart. The renal locations of both transporters largely resembled those in rats and mice; hSGLT2 and SGLT1 were localized to the brush border membrane (BBM) of proximal tubule S1/S2 and S3 segments, respectively. Different to rodents, the renal expression of hSGLT1 was absent in thick ascending limb of Henle (TALH) and macula densa, and the expression of both hSGLTs was sex-independent. In small intestinal enterocytes, hSGLT1 was localized to the BBM and subapical vesicles. Performing double labeling with glucagon-like peptide 1 (GLP-1) or glucose-dependent insulinotropic peptide (GIP), hSGLT1 was localized to GLP-1-secreting L cells and GIP-secreting K cells as has been shown in mice. In liver, hSGLT1 was localized to biliary duct cells as has been shown in rats. In lung, hSGLT1 was localized to alveolar epithelial type 2 cells and to bronchiolar Clara cells. Expression of hSGLT1 in Clara cells was verified by double labeling with the Clara cell secretory protein CC10. Double labeling of human heart with aquaporin 1 immunolocalized the hSGLT1 protein in heart capillaries rather than in previously assumed myocyte sarcolemma. The newly identified locations of hSGLT1 implicate several extra renal functions of this transporter, such as fluid absorption in the lung, energy supply to Clara cells, regulation of enteroendocrine cells secretion, and release of glucose from heart capillaries. These functions may be blocked by reversible SGLT1 inhibitors which are under development.

Superoxide dismutase and cytochrome P450 isoenzymes might be associated with higher risk of renal cell carcinoma in male patients.

Literature data support the hypothesis that oxidative stress and the accompanying antioxidant defense might play an important role in renal cell carcinoma (RCC) growth and progression. It is also known that the incidence of renal tumors is two times higher in men than in women. Thus, the aim of this study was to determine whether the oxidant/antioxidant profile of renal cell carcinoma tissue, adjacent to tumor tissue and nontumor tissue was different in male and female patients. Significantly higher lipid peroxidation (LPO) in renal cell carcinoma tissue compared to nontumor tissue was demonstrated only in male patients. Besides, gender-related difference in copper zinc superoxide dismutase (CuZnSOD) and manganese superoxide dismutase (MnSOD) in nontumor and renal cell carcinoma tissue was obtained at the level of transcription, translation and activity of these antioxidant isoenzymes. Morever, we demonstrated that the gene expression of 3 CYPs out of 7 was altered; CYP2D6 mRNA was decreased in both sexes while gender-related suppression of mRNA for CYP2E1 (women) and CYP2C19 (men) was observed. Taken together, these parameters might be potentially responsible for higher risk of renal cell carcinoma in men than in women.

[Urothelial carcinoma with an inverted growth pattern: a report of 4 cases]. / Urotelni karcinom invertiranog nacina rasta--prikaz 4 bolesnika.

AIM: Urothelial (transitional cell) tumors account for about 90% of all bladder tumors. Their presentation varies from benign lesions that rarely recur to highly malignant tumors. Inverted (endophytic) growth pattern in urothelial carcinoma is particulary hard to distinguish from inverted papilloma. Morphologic criteria alone are not enough and immunohistochemical assesments must also be done, especially in cases of small size biopsy material or transurethral resections. The aim of this study was to accentuate the importance and ways of differentiation of this variable forms as their treatment and prognosis differ. PATIENTS AND METHODS: In the period from 01.01.2008. to 30.06.2009. at Department of Pathology, University Hospital "Sestre milosrdnice" four patients were diagnosed with low-grade urothelial carcinoma with an inverted growth pattern. Routine histology and additional immunohistochemistry to p53, Ki-67 and CK 7 and 20 was performed. RESULTS: There were three male patients aging 37, 61 and 69 years and one female aged 46 (mean 53.3 years). Three patients presented with painless hematuria while the last patient had microhaematuria as an Incidental finding. Histologically, tumors formed nests of atypical urothelial cells. Very few or no mitotic figures were observed. Invasion of lamina propria was present in three specimens. Immunohistochemically, positive staining to p53 and CK 20 was observed in all four cases and staining to CK 7 in two. Staining to CK 20 was positive in 80%-100% of tumor cells while the number of p53 positive cells was between 20% and 40% in all four cases. Proliferative activity was assesed using Ki-67 antibody. The percentage of positively stained tumor cells, assesed in hot spots under high magnification (400x), was 5%, 7%, 8% and 12% (mean 8%). CONCLUSION: Urothelial carcinoma with inverted growth pattern and inverted papilloma have similar morphologic features but their biological behaviour, treatment and prognosis are different. In order to avoid the urothelial carcinoma to be misdiagnosed as a benign papilloma, we find it very important to make additional investigations beside conventional histology. Immunohistochemical staining for CK 20, p53 and Ki-67, which is positive in most carcinomas, can help us make the right diagnosis.

Posttraumatic high-flow priapism: case report, current management options and literature review.

A rare case of posttraumatic high-flow priapism is presented. A 20-year-old man underwent diagnostic procedure with color Doppler sonography and angiography. On color Doppler sonography and selective and supraselective angiographic images, arteriocavernosal fistula and pseudoaneurysm were detected in the proximal part of the right cavernous body. Complete detumescence of the penis was achieved by selective embolization with microcoil. No recurrence was observed and postoperative erectile function was incompletely restored. The clinical, diagnostic and therapeutic peculiarities of this rare condition are presented, along with review of the literature on the topic.

Seminal vesicle cyst with ectopic ureteral insertion and ipsilateral renal dysplasia--an unexpected diagnosis.

An extremely rare case of seminal vesicle cyst associated with ipsilateral renal dysplasia and ectopic ureter is presented. A 36-year-old patient underwent nephroureterovesiculectomy. Considering the clinical and imaging profile of the patient, a diagnosis of ureterocele with megaureter was initially suspected, but intraoperative findings and definitive pathological analysis of the specimen revealed right renal dysplasia with ectopic ureter opening into seminal vesicle cyst. The clinical and therapeutic peculiarities of this rare condition are presented and the literature on this topic is reviewed.

[Clinicopathological characteristics of micropapillary variant of urinary bladder carcinoma]. / Klinicko-patoloska obiljezja mikropapilarne varijante urotelnog karcinoma mokracnog mjehura.

Micropapillary urothelial carcinoma (MUC) is a rare variant of urinary bladder carcinoma associated with highly aggressive behaviour. The aim of this study was to analyse clinicopathological features of MUC particularly a relationship between pathological stage at presentation and proportion of micropapillary component (MPC) in 10 patients with MUC. In the examined period (January 1st 2004 - June 30th, 2007) there were 610 patients with urinary bladder cancer (M:F = 456:154), while 10 (1.6%) of them were patients with MUC. All MUC were invasive at the time of diagnosis. Stage distribution at presentation was 4 T1(40%) and 6 T2 (60%) and the percentage of MPC correlated with pathological stage: 3 of 4 (75%) tumors staged T1 had less than 10% of MPC and 5 of 6 (83,3%) tumors staged T2 had more than 50% of MPC. MUC is an aggressive tumor, often in advanced stage of disease at the time of diagnosis, in which the pathological stage is related to the proportion of MPC.

The incidence of hyperechoic prostate cancer in transrectal ultrasound-guided biopsy specimens.

OBJECTIVES: To estimate the incidence of transrectal ultrasound (TRUS) hyperechoic lesions and of hyperechoic prostate cancer in TRUS-guided biopsy specimens. METHODS: We prospectively studied 200 patients with total prostate-specific antigen values less than 20 ng/mL and/or positive results on digital rectal examination who had undergone TRUS-guided prostate biopsy. Each patient underwent laterally directed systemic six-core biopsy plus cores from abnormal TRUS lesions and rectally palpable lesions. Six to 10 biopsy cores were obtained from each patient. RESULTS: Hyperechoic lesions were found in 19 patients (9.5%), hypoechoic in 83 (41.5%), and isoechoic in 98 (49.0%). Prostate cancer was diagnosed in 33.0% of study patients. Isoechoic findings on TRUS were recorded in 31.8% of patients diagnosed with prostate cancer, whereas 60.6% of cancers had hypoechoic and 7.6% hyperechoic lesions. There was no significant difference in the mean Gleason score between isoechoic cancers (mean 5.4) and hypoechoic cancers (mean 5.6). However, hyperechoic cancers had a mean Gleason score of 7.0, which was higher when compared with isoechoic and hypoechoic cancers. CONCLUSIONS: Biopsy of hyperechoic lesions was positive for prostate cancer in a higher percentage of patients than previously reported in the literature, and Gleason score of these cancers was higher when compared with isoechoic and hypoechoic cancers.

Serum tPSA, cPSA, related density parameters and chromogranin A as predictors of positive margins after radical prostatectomy.

Serum levels of total prostate specific antigen (t-PSA) and PSA complexed to antichymotrypsin (PSA-ACT), as well as their corresponding density parameters were measured in prostate cancer (PC) candidates for radical prostatectomy. In these patients blood Chromogranin A (CgA) values were also recorded. The PSA-ACT recordings in presurgically characterized organ-confined disease were assumed to predict post-surgical staging better than t-PSA. If this proved correct the novel approach might contribute to the positive predictive value of Partin nomograms. In this prospective study 50 patients with clinically localized PC underwent staging pelvic lymphadenectomy and radical prostatectomy. The numerical values of the tPSA and PSA-ACT parameters were presurgically measured. The PSA and PSA-ACT densities (PSAD and ACTD) of the whole prostate were calculated by using transurethral ultrasound (TRUS) data. These preoperative results together with the CgA values were correlated with post-surgical pathological staging data. The relationships between serum tPSA, PSA-ACT, PSAD, ACTD, CgA and the final stage of prostatectomy specimens derived from the pathological data were analyzed. This preliminary study was performed on a relatively small number of patients who were characterized by a serum PSA <20 and a Gleason score (GS) < or =7. Nevertheless, the application of the logistic regression model showed both t-PSA and PSA-ACT to be superior to their density derivatives in predicting postsurgical pathological stage in PC patients who initially seemed to have localized prostate cancer. An elevation in serum CgA level, although rather infrequent at the early stages of PC is principally found in patients with higher Gleason score PC and was mostly associated with extracapsular tumor spread. Our results do not justify the substitution of PSA-ACT for t-PSA data in the Partin nomogram approach.

[Bilateral renal cell carcinoma and concomitant urothelial carcinoma of the renal pelvis and ureter: case report]. / Obostrani karcinom bubreznih stanica i istodobni urotelni karcinom nakapnice i mokracovoda: prikaz bolesnika.

We report a patient with ipsilateral synchronous renal cell carcinoma and urothelial carcinoma of the left renal pelvis and ureter. The patient underwent nephrectomy 9 years earlier due to renal cell cancer of the right kidney. Only 25 cases of ipsilateral synchronous renal cell carcinoma and urothelial carcinoma have been reported in the literature. The median age at diagnosis was 65 years, hematuria was the most common presentation and 24% of patients had metastases at first examination. Approximately one fourth of the patients had a history of cigarette smoking. There is no proof about higher histopathological grade of malignancy or specific histological pattern of these tumors when they occur synchronously. In the literature there is no report on the synchronous occurrence of renal cell carcinoma and urothelial carcinoma of both the renal pelvis and ipsilateral ureter.

Evolution of the clinical presentation and outcomes after radical prostatectomy for patients with clinically localized prostate cancer--changing trends over a ten year period.

We demonstrate the evolution of the clinical presentation and outcomes for patients with clinically localized prostate cancer (PC) treated with radical retropubic prostatectomy (RRP) at our department, emphasizing epidemiologic significance of changes during the 10-year period. We assessed the annual trends for changes in patients age, preoperative prostate specific antigen (PSA), preoperative versus postoperative stages and Gleason grades, organ confined status and surgical margin status. A total of 488 RRPs were performed from January 1996 to December 2005 with the annual frequency increased from 8 to 129 (1512.5%). Mean patient age increased from 61.5 to 66.12 years in 2005, with the percentage of men aged more than 70 years increased from 12.5 to 26.5%, respectively. The detection of PC based solely on pathological PSA levels (as indication for prostate biopsy) rose impressively from 25.5 to 70% and the rates of postoperative organ-confined disease also increased significantly from 25 to 74.7%. Mean preoperative PSA decreased from 16.7 to 9.89 ng/mL. On the contrary, there was an increase in percentage of patients with preoperative PSA values ranging from 4 to 10 ng/mL (from 20 to 65.4%). Positive surgical margin rate decreased from 49.4 to 25% and percent of patients receiving neoadjuvant therapy decreased from 78.5 to 5.4%. Proportion of patients who were undergraded decreased from 75.1 to 31.7%. The rates of understaging have remained relatively stable over the years. During the study period, PC was increasingly detected by prostate biopsy on the basis of a pathological PSA level only and shifted significantly to more organ-confined stages with more favourable outcomes for pathological variables due to a more accurate assessment of clinical stage prior to surgery, reduced use of neoadjuvant therapy and improved surgical technique. Our data also argue strongly that routine PSA testing should be expanded and not restricted.

Radical prostatectomy in a patient with osteogenesis imperfecta: a possible surgical trap.

An exceedingly rare case of a patient with osteogenesis imperfecta and prostate cancer is reported. The patient underwent radical prostatectomy, which had to be stopped due to the extremely narrow space for surgical manipulation. The clinical, diagnostic and operative peculiarities of the case are presented and the relevant literature reviewed.

Systemic stress responses in patients undergoing surgery for benign prostatic hyperplasia.

OBJECTIVE: To determine differences in systemic stress responses in patients undergoing three different types of surgery for benign prostatic hyperplasia (BPH), evaluated by measuring levels of stress variables, i.e. cortisol; acute-phase reactants, i.e. C-reactive protein (CRP) and fibrinogen; and antioxidants, i.e. total antioxidant status (TAS) and superoxide dismutase (SOD). PATIENTS AND METHODS: The study included 80 patients who fulfilled the inclusion criteria for surgery for BPH. Based on an ultrasonographic estimate of the prostate volume before surgery, all patients were allocated to one of three groups; group 1, prostate < or = 30 g and treated with transurethral incision of the prostate (TUIP); group 2, prostate 30-80 g, treated with transurethral resection of the prostate (TURP); and group 3, prostate >80 g, treated with a suprapubic transvesical prostatectomy (TP). Blood samples were taken from each patient on the day before and the day after surgery, and the acute-phase reactants and antioxidants measured; cortisol concentrations were also measured in 24-h urine samples the day before and 3 days after surgery. RESULTS: There were significantly higher levels of cortisol, CRP and TAS, and significantly lower levels of fibrinogen and SOD in all study groups after surgery than before. Surgery and associated conditions, e.g. excitement, fear, blood loss, etc., lead to traumatic and oxidative stress, followed by a strong systemic stress response during and after surgery. Low fibrinogen levels after surgery had a different pattern from the other acute-phase reactants, as a result of increased fibrinolytic activity after TURP and TP. CONCLUSION: The extent of the systemic stress response correlated fairly well with the degree of tissue damage, which differed in the three groups. Suprapubic TP caused the most tissue trauma and triggered the strongest systemic stress response. This response was moderate after TURP, while TUIP (a minor intervention) caused the least stress. Specific changes in stress markers could be used to improve surgery for BPH. Whether there is a benefit of antioxidant therapy during surgery for BPH should be evaluated in further studies.

Giant testicular mixed germ cell tumor. a case report.

OBJECTIVE: We report a case that we believe to be the largest example of a testicular mixed germ cell tumor with a clearly defined histology pattern. CLINICAL PRESENTATION AND INTERVENTIONS: A 21-year-old patient consulted a urologist concerning a giant testicular mass. At the time of presentation the tumor measured 29 x 20 x 16 cm, with a weight of 4,850 g. Serum alpha-fetoprotein was over 15,000 ng/ml, while beta-human chorionic gonadotropin was normal. Chest X-ray and CT revealed multiple bilateral metastases. Histopathology revealed a mixed germ cell tumor containing 80% of yolk sack tumor, 10% of teratoma and 10% of embryonal carcinoma. Orchiectomy and chemotherapy were successful in the treatment of primary tumor and bilateral lung metastases. CONCLUSION: This tumor grew to extraordinary dimensions because of the patient's failure, due to fear, lack of knowledge and embarrassment, to seek medical help and to health professionals' negligence when performing regular check-ups.

Tumors in kidney fusion anomalies--report of five cases and review of the literature.

OBJECTIVE: Fusion anomalies of the kidney are rarely encountered and the association of malignant tumors with such conditions is exceedingly rare. Association of tumors with horseshoe kidney is also uncommon, with fewer than 200 cases having been reported in the literature, and the association of tumors with crossed-fused ectopia is even rarer, with only four cases having been reported so far. MATERIAL AND METHODS: During the past decade five patients with fusion anomalies have been treated for tumors in our clinic, four of whom had horseshoe kidney and one of whom had crossed-fused left-to-right ectopia. The clinical, diagnostic and operative peculiarities of each case are presented and the recent literature on this topic is reviewed. RESULTS: Two patients were diagnosed with renal cell carcinoma, two had transitional cell carcinoma and one had oncocytoma. CONCLUSIONS: The commonest tumor reported in kidney fusion anomalies is renal cell carcinoma, although its reported incidence is no higher than that in the normal population. In the case of transitional cell carcinomas, diagnosis is usually made at an advanced stage. The value of thorough urologic and radiological investigations is stressed. Angiography, whether classical or in combination with multi-slice CT, is considered essential in order to confirm renal anomalies and the tumor situation and to plan the surgical approach. In our experience, radical nephrectomy with isthmus division via a transperitoneal approach is the treatment of choice.

[Guidelines for antimicrobial treatment and prophylaxis of urinary tract infections]. / Smjernice antimikrobnog lijecenja i profilakse infekcija mokracnog sustava.

Recommendations for antimicrobial treatment and prophylaxis of urinary tract infections (UTI) have been made according to the results of investigation of resistance of the most frequent causative agents of UTI to antimicrobial drugs. This investigation has been conducted for the past seven years by the Committee for monitoring bacterial resistance to antibiotics in the Republic of Croatia, with consensus of eight professional societies of the Croatian Medical Association. Uncomplicated cystitis is treated 1, 3, or 7 days, complicated 7 days, pyelonephritis 10-14 days, and complicated UTI 7 to 14 days, rarely longer. For the treatment of cystitis fluorokinolons, nitrofurantoin, betalactam antibiotics, and in the fields of lower resistance trimethoprim/sulfamethoxazol are being used. Single treatment with fluorokinolons is administered to otherwise healthy young women with normal urinary tract in whom cystitis symptoms have been present for less than 7 days. Empiric antimicrobial treatment of pyelonephritis, recurrent and all complicated UTI must be reviewed after urine culture finding is obtained. In the treatment of bacterial prostatitis and febrile UTI in males, the drug of first choice is ciprofloxacin. Asymptomatic bacteriuria (AB) is treated in pregnant women, newborns, preschool children with urinary tract abnormalities, before invasive urologic and gynecologic procedures, in kidney transplant recipients, and in the first days of short term urinary bladder catheterization. Recommendations for the treatment of AB in patients with diabetes mellitus have been controversial in the past two years. Antimicrobial prophylaxis is administered mostly one hour prior to the diagnostic or therapeutic invasive urological procedure, using selected antimicrobial agents.

Periacinar retraction clefting in the prostatic needle core biopsies: an important diagnostic criterion or a simple artifact?

The diagnosis of prostatic adenocarcinoma in needle core biopsy is based on major and supportive criteria. One of the supportive criteria is the presence of retraction clefting around neoplastic glands. We analyzed a series of 137 prostatic cancer cases diagnosed by needle core biopsy to determine the frequency, extent and criteria for periacinar retraction clefting. Clefting was analyzed on ten neoplastic and ten normal glands in three different high power fields. One-third or more glands with clefts affecting more than 50% of circumference were significantly more common in tumors (51.8%) than in benign glands (8%) (P<0.0001). A stricter criterion that designated as positive the cases with at least 50% of neoplastic glands (15 of 30) with clefts that affected more than 50% of circumference revealed clefts in only 15.3% of the malignant cases but none in benign cases (0%) (P<0.0001). Regardless of their extension, 15 or more glands with clefts were also more prominent in malignant cases (86.9%) than in benign cases (20.4%) (P<0.0001). We conclude that periacinar retraction clefting represents a reliable criterion for diagnosis of the prostatic adenocarcinoma, especially in cases with clefts affecting more than 50% of circumference in at least 50% of suspicious glands.