DIAGNOSTIC UTILITY OF IMMUNOHISTOCHEMICAL EXPRESSION OF KI!67, P63 AND AMACR IN PROSTATE INTRAEPITHELIAL NEOPLASIA.

OBJECTIVE: The aim: To determine malignant transformation and progression ability of high grade and low grade prostate intraepithelial neoplasia with the help of immunohistochemical method. PATIENTS AND METHODS: Materials and methods: The results of examination of 93 patients with PIN (50 patients with high grade PIN and 43 patients with low grade PIN) were assessed comparatively using immunohistochemical markers. Semiquantitative method was used to evaluate !"-67, #63 and AMACR tissue expression with four grades from "+" to "++++" or from 1 to 4 points: '+' - low reaction, '++' - poor reaction, '+++' - moderate reaction and '++++" - intense reaction. RESULTS: Results: There were statistically significant differences in immunohistochemical expression rates between HGPIN and LGPIN. Patients with HGPIN had higher Ki-67 and AMACR expression rate and lower p63 expression rate than patients with LGPIN. Intense and moderate Ki-67 expression was detected in HGPIN more often, in 24 % and 11 % respectively. Low and moderate AMACR expression was determined in HGPIN more often, in 28 % and 5 % respectively. Low and not evident p63 expression was observed in HGPIN more often, in 36 % and 8 % respectively. CONCLUSION: Conclusions: HGPIN has common morphological peculiarities with prostate adenocarcinoma. Immunohistochemical detection of Ki-67, p63 and AMACR is aimed to differentiate among patients with PIN a group of high malignant transformation risk.

The changes and updates in the fifth edition of the WHO Classification of prostate tumors.

The fifth edition of the WHO classification of prostate tumors provides new insight into prostate cancer pathogenesis supported by molecular data. It discards the terms low-grade PIN and high-grade PIN. The new entity „Treatment-related neuroendocrine prostatic carcinoma“ is introduced. The importance of the diagnosis of intraductal carcinoma is highlighted. The terminology of prostatic basocellular carcinoma is upgraded. Some cancer subtypes are being relocated to different chapters based on new findings. Also, the role of the prostate as an origin of hereditary cancer is stressed. Finally, the new therapeutic approaches are mentioned.

PIN-like ductal carcinoma of the prostate has frequent activating RAS/RAF mutations.

AIMS: Prostatic intraepithelial neoplasia-like (PIN-like) ductal carcinoma is a rare tumour characterised by often cystically dilated glands architecturally resembling high-grade PIN, but lacking basal cells. These tumours are frequently accompanied by grade group 1 acinar cancer and behave relatively indolently. In contrast, conventional ductal adenocarcinoma of the prostate is an aggressive variant comparable to grade group 4 acinar cancer. Here, we used targeted next-generation sequencing to molecularly profile PIN-like ductal carcinoma cases at radical prostatectomy. METHODS AND RESULTS: Five PIN-like ductal carcinoma samples at radical prostatectomy with sufficient tumour tissue available were analysed for genomic alterations by targeted next-generation sequencing using the Johns Hopkins University (JHU) solid tumour panel. DNA was captured using SureSelect for 640 genes and sequenced on the Illumina HiSeq platform. Three of five (60%) of the PIN-like ductal carcinomas showed activating mutations in the RAS/RAF pathways, which are extraordinarily rare in conventional primary prostate carcinoma (<3% of cases), including an activating hot-spot BRAF mutation (p.K601E), an activating hot-spot mutation in HRAS (p.Q61K) and an in-frame activating deletion in BRAF (p.T488_Q493delinsK). An additional two cases lacked BRAF or HRAS mutations, but harboured in-frame insertions of uncertain significance in MAP2K4 and MAP3K6. One case had sufficient acinar tumour for sequencing, and showed a similar molecular profile as the concurrent PIN-like ductal carcinoma, suggesting a clonal relationship between the two components. CONCLUSIONS: PIN-like ductal carcinoma represents a molecularly unique tumour, enriched for potentially targetable oncogenic driver mutations in the RAS/RAF/MAPK pathway. This molecular profile contrasts with that of conventional ductal adenocarcinoma, which is typically enriched for pathogenic mutations in the mismatch repair (MMR) and homologous recombination (HR) DNA repair pathways.

Comparative study of immunohistochemical expression of ERG and MAGI2 in prostatic carcinoma.

Diagnosis of Prostatic adenocarcinoma (PAC) is still a problematic issue. The objective of this study was to evaluate the diagnostic and prognostic value of ERG immunohistochemical (IHC) expression compared to MAGI2. MATERIALS AND METHODS: This study was conducted on 56 cases of PAC and 29 cases of nodular prostatic hyperplasia (NPH). IHC staining for ERG and MAGI2 was applied to archival formalin-fixed paraffin-embedded blocks. Semi-quantitative scoring was compared and correlated with clinicopathologic parameters and the Ki-67 index. RESULTS: Revealed positive ERG in 51.8% of PAC while all NPH cases were negative. On the other hand, MAGI2 was detected in 91.1% of PAC versus 17.2% of NPH. Using ROC curve, the ERG showed 53.6% sensitivity, 100% specificity, 76.5% diagnostic accuracy (DA) and area under the ROC curve 0.768 in comparison to MAGI2 that showed (91.1%, 86.2%, 88.25% and 0.948 respectively). Analysis of the combined use of the two markers revealed 95% sensitivity, 100% specificity, and 94% DA when tested synchronously. Moreover, a statistically significant inverse relationship could be detected between ERG expression and the Gleason grading group (P = 0.01) and Ki-67 index (P < 0.001). In addition, high-grade prostatic intraepithelial neoplasia (HGPIN) adjacent to carcinoma; showed positive expressions in (1/11 cases, 9.11%) for ERG and (6/11 cases, 54%) for MAGI2. CONCLUSION: This study recommends using both ERG and MAGI2 in a cocktail for better diagnostic validity of PAC. Only ERG expression could be a good prognostic indicator.

The impact of metformin use on the risk of prostate cancer after prostate biopsy in patients with high grade intraepithelial neoplasia.

PURPOSE: We report our experience on metformin use in diabetic patients and its impact on prostate cancer (PCa) after a high-grade prostatic intraepithelial neoplasia (HGPIN) diagnosis. MATERIALS AND METHODS: We retrospectively analyzed 551 patients with a diagnosis of HGPIN without PCa in a first prostate biopsy. The cohort of the study consisted of 456 nondiabetic subjects, and 95 diabetic patients. Among the patients with diabetes 44 were treated with metformin, and 51 with other antidiabetic drugs. A transrectal ultrasound prostate biopsy scheme with 22 cores was carried out 4-6 months after the first diagnosis of HGPIN. RESULTS: Among 195 (35.4%) patients with cancer, there were statistically significant differences in terms of PCa detection (p<0.001), Gleason score distribution (p<0.001), and number of positive biopsy cores (pv0.002) between metformin users and non-users. Metformin use was associated with a decreased risk of PCa compared with neveruse (p<0.001). Moreover, increasing duration of metformin assumption (≥2 years) was associated with decreasing incidence of PCa and higher Gleason score ≥7 compared with assumption <2 years. CONCLUSIONS: This preliminary experience suggests that metformin use may have some beneficial effects in patients with diabetes and HGPIN; metformin should not be overlooked in these patients because it is neither new nor expensive.

[Fatty acid synthase in the diagnosis of prostate neoplasms]. / FASN v diagnostike novoobrazovanii predstatel'noi zhelezy.

The differential diagnosis of benign and malignant changes in the prostate presents still definite difficulties; the antibody panel existing for these purposes is imperfect. Fatty acid synthase (FASN) is an androgen-regulated enzyme required for de novo lipogenesis. A number of studies have noted increased expression of the gene encoding this protein in tumors and precancerous lesions of different locations. AIM: Тo estimate the diagnostic value of analyzing the expression of FASN in prostate neoplasias. MATERIAL AND METHODS: Surgical specimens were selected for study from 71 patients with prostate cancer during radical prostatectomy. An immunohistochemical method was used to analyze FASN expression. RESULTS: The expression of FASN was observed to be moderate or intensive in adenocarcinoma and high-grade prostatic intraepithelial neoplasia (hPIN) in all the study samples while 2 cases showed none and weak expression of AMACR. In benign lesions, the expression of this protein was identified only in 3 cases and it was characterized by a low-intensity staining. CONCLUSION: The study has shown that the high frequency of FASN expression in hPIN and cancer and no expression in most structures of benign hyperplasia make it possible to use this protein as an additional marker in the differential diagnosis of prostatic neoplasms.

Mutation Profiling Indicates High Grade Prostatic Intraepithelial Neoplasia as Distant Precursors of Adjacent Invasive Prostatic Adenocarcinoma.

INTRODUCTION: High Grade Prostatic Intraepithelial Neoplasia (HGPIN) is the putative precursor lesion to prostatic adenocarcinoma (PCa), but the precise relationship between HGPIN and PCa remains unclear. METHODS: We performed a molecular case study in which we studied mutation profiles of six tumor-associated HGPIN lesions in a single case of TMPRSS2:ERG fusion positive Gleason score 7 PCa that we had previously mapped for somatic mutations in adjacent Gleason patterns 3 and 4 foci, using microdissection and targeted deep-sequencing. RESULTS: A total of 32 tumor-specific mutated sites were successfully amplified and sequenced, including 25 truncal mutations and 7 mutations that were specific to either the Gleason pattern 3 or pattern 4 foci. All six HGPIN foci shared the same tumor-specific TMPRSS2:ERG fusion breakpoint, establishing that they were all clonally related to the adjacent invasive tumor. Among the 32 gene targets mutated in the invasive tumor, only mutation of the OR2AP1 gene, a truncal mutation, was found in a single focus of HGPIN. The remaining gene targets that were successfully sequenced were wild-type in all other HGPIN foci. DISCUSSION: This study demonstrates the feasibility of targeted mutation profiling of HGPIN lesions, which will be important to understand PCa tumorigenesis. The results in this case, showing a remarkable absence of truncal mutations in HGPIN lesions bearing the tumor-specific ERG fusion, indicate HGPIN lesions may be relatively stable genetically and argue against a stepwise clonal evolution model of HGPIN to PCa. Prostate 76:1227-1236, 2016. © 2016 Wiley Periodicals, Inc.

Pseudohyperplastic prostate carcinoma: histologic patterns and differential diagnosis.

The similarity between some carcinomas and many benign glandular proliferations has been mentioned in the literature for decades. The description of the main histologic features of pseudohyperplastic carcinoma has been very useful in avoiding errors of interpretation, particularly false-negative results. In recent years, we have found some histologic variants of this neoplasm that have not been mentioned previously. In order to classify the different histologic growth patterns and comment on their differential diagnosis, we reviewed the architectural and cytologic features of 34 cases of pseudohyperplastic adenocarcinoma in 2 radical prostatectomies, 4 transurethral resections, and 28 needle biopsies. Growth patterns most commonly observed included nodular, complex, and mixed (nodular and complex) patterns. Other less frequent histologic varieties included adenosis-like pattern, prostatic intraepithelial neoplasia-like pattern, pseudohyperplastic adenocarcinoma with xanthomatous features, and limited pseudohyperplastic adenocarcinoma. Frequent changes in neoplastic glands included papillary infoldings, large/cystic glands, and branching. Criteria associated with malignancy include nuclear enlargement (92%), apparent nucleoli (85%), pink amorphous secretions (78%), and transition to small acinar carcinoma (70%). However, in some biopsies, nuclear atypia was little apparent. Fifteen of the 34 cases were misdiagnosed as benign and 5 as other malignant neoplasms, and included the following diagnoses: hyperplastic nodules (11), prostatic adenosis (2), diffuse adenosis of the peripheral zone (1), benign cystic glands (1), and less frequently other malignant tumors including xanthomatous carcinoma (2), low-grade prostatic adenocarcinoma (2), and atrophic carcinoma (1). It is important to recognize the different growth patterns of this neoplasm in order to avoid an underdiagnosis of malignancy.

[Diagnostic value of estimation of ERG expression in prostate adenocarcinoma and high-grade prostatic intraepithelial neoplasia].

OBJECTIVE: to estimate the diagnostic and prognostic value of analyzing the abnormal overexpression of the chimeric protein ERG, encoded by the chimeric gene TMPRSS2/ERG, in prostatic neoplasias. MATERIAL AND METHODS: A total of 100 prostate adenocarcinoma samples were examined. The presence of tumor and high-grade prostatic intraepithelial neoplasia (hPIN) was verified by immunohistochemical tests using anti-P504S and anti-34ßE12 antibodies in serial sections; RT-PCR was employed to analyze the chimeric transcript TMPRSS2/ERG in 30 prostate adenocarcinoma samples. RESULTS: ERG expression was noted in 46% of the adenocarcinomas and in 21% of hPIN. Eight (8%) patients were observed to have heterogeneous ERG expression: the marked reaction in some tumor portions was concurrent with its complete absence in others. Furthermore, there was ERG expression in all cases of intraductal (noninvasive) carcinoma (the foci of intraductal carcinoma were assessed as atypical cribriform lesions by light microscopy). The prognostic value of ERG expression could not be determined at the current stage of the investigation. CONCLUSION: The relatively low rate of ERG-positive hPIN counts in favor of the limited role of this marker in the differential diagnosis of hPIN. ERG in combination with P504S and 34ßE12 is an informative marker for the differential diagnosis of hPIN with intraductal carcinoma.

Telomerase as a tumor marker in diagnosis of prostatic intraepithelial neoplasia and prostate cancer.

BACKGROUND: Early diagnosis of prostate cancer (CaP) can be addressed by studying prostatic intraepithelial neoplasia (PIN) as precancer (high-grade PIN or HGPIN). This article attempts to analyze the diagnostic role of telomerase as an early marker of carcinogenesis. METHODS: Complex urological patient evaluation and assessment of telomerase activity. RESULTS: Out of 92 patients 44% were diagnosed with CaP, 49% with low-grade PIN (LGPIN) in association with benign prostatic hyperplasia (BPH), and 7% with HGPIN in association with BPH. Active telomerase (AT) in prostate biopsy specimens was detected in 98% of patients with CaP, in 33% of patients with HGPIN, and in 20% of patients with LGPIN. In the event of simultaneous detection of AT and PIN in initial prostate biopsy specimens, further monitoring for 0.5-4.0 years revealed CaP development in 50-56% of cases. Further follow-up of patients with PIN and absent telomerase activity in initial biopsy specimens did not demonstrate the development of CaP. The PSA level was significantly higher in patients with active telomerase in the prostate tissue than in telomerase negative patients. CONCLUSIONS: Telomerase activity in the prostate tissue increases the risk of CaP development in patients with PIN. Detection of telomerase activity in prostate biopsy specimens from patients with PIN enables selection of a group of patients with high risk of CaP development and reduction of the number of prostate biopsies performed in other patients.

Prostate biopsy: results and advantages of the transperineal approach--twenty-year experience of a single center.

PURPOSE: Detection rate for prostate cancer (PCa) and complications following transperineal prostate biopsy (TPBx) were reported. METHODS: From January 1991 to December 2012, 4,000 men underwent TPBx; from 1991 to 2001, the patients underwent biopsy for suspicious DRE or PSA values >4 ng/mL; moreover, from 2002, the indications were abnormal DRE, PSA >10 ng/mL, PSA values between 4.1 and 10, 2.6 and 4 and <2.5 ng/mL with F/T PSA <25, <20 <15 %, respectively. In case of initial biopsy, the number of needles cores increased from 6 (1991-1996) to 12 (1997-2012) and 18 cores (2002-2012); in case of repeat biopsy, since 2005 a saturation biopsy (SPBx) with >24 cores was performed. RESULTS: Overall, PCa, normal parenchyma, HGPIN and ASAP were found in 1,379 (34.5 %), 2,400 (60 %), 175 (4.4 %) and 46 (1.1 %) patients, respectively; in case of initial TPBx, the scheme at 18 showed a greater PCa detection in comparison with scheme at 6-12 cores (p < 0.05). In case of repeat biopsy, a higher detection of microfocus of cancer was found performing a SPBx; moreover, 15 % of cancers were localized in the anterior zone. Incidence of hemospermia and urinary retention were correlated with the number of needle cores resulting equal to 30.4 versus 11.1 % in case of SPBx (p < 0.05); moreover, none developed sepsis. CONCLUSIONS: Transperineal prostate biopsy (TPBx) resets the risk of sepsis; moreover, in case of repeat SPBx, the transperineal approach detects a high number of significant PCa localized in the anterior zone (15 % of the cases).

Low prostate concentration of lycopene is associated with development of prostate cancer in patients with high-grade prostatic intraepithelial neoplasia.

Prostate cancer (PC) is a frequent male malignancy and represents the second most diagnosed cancer in men. Since pre-cancerous lesions, i.e., the high-grade prostatic intraepithelial neoplasia (HGPIN), can be detected years before progression to PC, early diagnosis and chemoprevention are targeted strategies to reduce PC rates. Animal studies have shown that lycopene, a carotenoid contained in tomatoes, is a promising candidate for the chemoprevention of PC. However, its efficacy in humans remains controversial. The present study aimed to investigate the relevance of plasma and prostate concentration of lycopene after a lycopene-enriched diet in patients diagnosed with HGPIN. Thirty-two patients diagnosed with HGPIN were administered a lycopene-enriched diet (20-25 mg/day of lycopene; through 30 g/day of triple concentrated tomato paste) for 6 months. A 6-month follow-up prostate biopsy assessed progression to PC. Patients were classified into three groups according to the histopathological features of the 6-month follow-up biopsy results: prostatitis; HGPIN and PC. PSA and plasma lycopene levels were measured before and after the dietary lycopene supplementation. Prostatic lycopene concentration was only assessed after the supplementation diet. Only prostatic lycopene concentration showed significant differences between the three groups (p = 0.03). Prostatic lycopene concentration below a 1 ng/mg threshold was associated with PC at 6-month follow-up biopsy (p = 0.003). We observed no overall benefits from a 6-month lycopene supplementation, as the rate of HGPIN progression to PC in our population (9/32, 28%) was similar to rates reported in the literature. Baseline PSA levels also showed no significant changes after a lycopene-enriched diet. Our findings point to prostatic lycopene concentration as a promising biomarker of PC. Further prospective longitudinal studies are needed to assess the prognostic role of prostatic lycopene in PC.

Therapeutic effects of finasteride: inhibition of disease progression and serum prostate-specific antigen reduction in patients with prostatic intraepithelial neoplasia.

The objective of this study was to evaluate the impact of finasteride on the progression of prostate intraepithelial neoplasia and levels of prostate-specific antigen (PSA) in patients. A total of 120 patients with high-grade prostatic intraepithelial neoplasia were included in this study from January 2013 to January 2018. All patients underwent prostate biopsies. Among them, 60 patients were assigned to the observation group and received a daily dosage of 5 mg finasteride for 60 months, while the remaining 60 patients were assigned to the control group and did not receive finasteride. PSA levels were measured every six months, and imaging scans were conducted throughout the five-year study period. Additional biopsies were performed if PSA levels exceeded 10 ng/mL or imaging suggested the presence of prostate cancer. Statistical analysis was applied to the collected data. In total, 25 cases of prostate cancer were identified in this study. Of these cases, 7 patients belonged to the observation group, whereas the remaining 18 patients were from the control group. The observation group exhibited significantly lower levels of total serum PSA (p < 0.001) and Gleason scores (p < 0.001) compared to the control group. Our study, which involved 120 participants, demonstrated that finasteride effectively reduces serum PSA levels and mitigates the severity of prostate cancer. These findings suggest that finasteride holds potential as a treatment option for patients with -high-grade prostatic intraepithelial neoplasia.

Alpha methylacyl-CoA racemase (AMACR) in prostate adenocarcinomas from Japanese patients: is AMACR a "race"-dependent marker?

BACKGROUND: Alpha methylacyl-CoA racemase (AMACR) is a useful diagnostic marker for prostate adenocarcinoma. However, its usefulness has not been fully validated in Japanese patients. The aim of this study was to evaluate the diagnostic utility of AMACR in prostate needle biopsy examination in Japanese patients. METHODS: A total of 119 prospective consecutive prostate needle biopsy specimens (680 cores) obtained from Japanese patients were examined. Sixty patients had adenocarcinoma (adenocarcinoma, 160 cores; benign, 204 cores), 14 patients had high-grade prostatic intraepithelial neoplasia (HGPIN; 19 cores), and 45 patients did not have any neoplastic lesions (297 cores). AMACR expression was scored semi-quantitatively as 0 (no expression), 1+ (partial and/or weak expression), or 2+ (strong, circumferential expression). The number of positively stained glands was counted. RESULTS: 2+ AMACR expression was observed in 70.1% of adenocarcinoma cases and in 52.6% of HGPIN cases. Of the adenocarcinoma cases showing 2+ AMACR expression, 34.8% demonstrated a heterogeneous expression pattern, with 1-75% of AMACR-positive glands. Three hundred eighty-five of the benign glands with an adenocarcinoma component showed 2+ AMACR expression (35 cases, 94 cores). 2+ AMACR expression was observed in 67 non-neoplastic benign glands (9 cases, 19 cores). CONCLUSIONS: The sensitivity and specificity of AMACR for the diagnosis of prostate adenocarcinoma and benign glands in Japanese patients are lower than those previously reported in Western countries. Pathologists should be cautious while interpreting AMACR expression pattern in Japanese patients.

Use of PCA3 in detecting prostate cancer in initial and repeat prostate biopsy patients.

BACKGROUND: The PCA3 urinary assay has shown promise in predicting the presence of prostate cancer. We evaluated the value of this test in patients undergoing initial and repeat prostate biopsy. METHODS: PCA3 and PSA levels were obtained from 456 men with no known personal history of prostate cancer prior to prostate biopsy. Two hundred eighty-nine men underwent an initial prostate biopsy and 167 underwent a repeat prostate biopsy. PCA3 and PSA levels were compared to the prostate biopsy results. RESULTS: PCA3 score was shown to be independent of prostate volume (P = 0.162) and PSA level (P = 0.959). PCA3 scores were significantly higher in patients with cancer on prostate biopsy compared to patients with negative biopsy results (P < 0.0001). In logistic regression, PCA3 showed a significantly higher AUC than PSA (0.726 vs. 0.512, P = 0.0001). This difference persisted when examining the initial biopsy subgroup, with PCA3 out-performing PSA (AUC 0.772 vs. AUC = 0.552, P < 0.0001), but not in the repeat biopsy subgroup (AUC = 0.605 vs. AUC = 0.500, P = 0.2488). CONCLUSIONS: PCA3 was found to be a better predictor of prostate cancer than PSA in the total population as well as the initial biopsy population, but was not superior to PSA in the repeat biopsy population. Prostate 73: 48-53, 2013. © 2012 Wiley Periodicals, Inc.

Cytoplasmic PTEN protein loss distinguishes intraductal carcinoma of the prostate from high-grade prostatic intraepithelial neoplasia.

Intraductal carcinoma of the prostate is a marker of aggressive disease. However, intraductal carcinoma exists on a morphologic continuum with high-grade prostatic intraepithelial neoplasia (PIN) and distinguishing intraductal carcinoma from PIN is a common diagnostic dilemma with significant clinical implications. We evaluated whether immunostains for PTEN and ERG can sensitively identify intraductal carcinoma and accurately distinguish it from high-grade PIN. A combined immunostain for PTEN, ERG, p63 and CK903 was developed and validated. Radical prostatectomy specimens with lesions meeting criteria for intraductal carcinoma (n=45), intraductal cribriform proliferations falling short of intraductal carcinoma (n=15), and PIN lesions (n=39) were retrospectively identified and assessed for PTEN and ERG. Cytoplasmic PTEN loss was identified in 84% (38/45) of the intraductal carcinoma and 100% (15/15) of intraductal cribriform proliferation cases. In contrast, cytoplasmic PTEN loss was never observed in PIN (0/39; P<0.0001). Of the 53 cases of intraductal carcinoma or intraductal cribriform proliferation with cytoplasmic PTEN loss, it was homogeneously lost in 42 cases (79%). Weak, focal nuclear positivity for PTEN was retained in 31 of these 42 cases (74%). ERG expression was identified in 58% (26/45) of intraductal carcinoma and 67% (10/15) of intraductal cribriform proliferations compared with 13% (5/39) of PIN. Concordance between the PTEN/ERG status of the intraductal carcinoma lesions and the concurrent invasive carcinoma was high (>95% and P<0.0001 for each), and substantially less for PIN and the concurrent invasive tumor (83% for PTEN and 67% for ERG; P=NS for each). Cytoplasmic PTEN loss occurs in the majority of intraductal carcinoma and intraductal cribriform proliferation cases. Cytoplasmic PTEN loss was never observed in PIN (100% specificity). Our study identifies PTEN loss as a potentially useful marker to distinguish intraductal carcinoma from PIN and provides a plausible molecular explanation for why intraductal carcinoma is associated with poor prognosis.

Clinical applications of novel ERG immunohistochemistry in prostate cancer diagnosis and management.

TMPRSS2:ERG gene fusions, the most common molecular subtype of ETS family gene fusions occur in ~50% of prostate carcinomas (PCas) and ~20% of high-grade prostatic intraepithelial neoplasia (HGPIN) intermingled with adjacent PCa demonstrating identical gene fusions. ERG gene fusions have not yet been demonstrated in isolated benign prostate tissue, isolated high-grade prostatic intraepithelial neoplasia, or benign cancer mimics. Taken together, ERG gene fusions are the most prostate cancer-specific biomarker yet identified and define a specific molecular subtype of PCa with important clinical and biological implications. ERG gene fusions result in the overexpression of a chimeric fusion transcript that encodes a truncated ERG protein product. Recently, N-terminal epitope-targeted mouse (9FY) and C-terminal-targeted rabbit monoclonal (EPR 3864) ERG antibodies are commercially available and are increasingly utilized as a surrogate for TMPRSS2:ERG gene fusions. Until recently, because of lack of availability of reliable ERG antibody, the most commonly utilized methods for studying ERG aberrations in PCa specimens included fluorescence in situ hybridization or reverse transcriptase polymerase chain reaction. The knowledge gleaned from these studies has significantly improved our understanding of molecular biology of ERG gene fusions. With availability of highly specific anti-ERG monoclonal antibodies, there are now unprecedented opportunities to explore and validate clinical applications of ERG antibody in routine pathology practice, which has just started. This review provides a brief background of molecular biology of ERG gene fusions in PCa and focuses on characterizing the current state of ERG oncoprotein and determining the role of ERG immunohistochemistry in the diagnosis and biological stratification of prostate cancer.

Needle biopsy findings in prostatic adenocarcinoma: experience at a tertiary care center in a developing country.

The objectives of this study are to report the findings in prostatic needle biopsies positive for cancer seen in our practice with regard to the frequency of cancer detected at various sites, the cancer volume, Gleason grade, presence of perineural invasion, and others; to correlate cancer volume with Gleason grade, perineural invasion, and serum prostate-specific antigen (PSA) levels; and to correlate Gleason grade with serum PSA levels. The study was conducted at The Section of Histopathology, Department of Pathology and Microbiology, Aga Khan University Hospital, Karachi, Pakistan. All consecutive needle biopsies received from January 1, 2011 to June 30, 2012, which were positive for prostatic adenocarcinoma, were included in the study. Statistical analysis was carried out using SPSS 19.0 software package (SPSS Hong Kong Headquarters, Quarry Bay, Hong Kong). A total of 97 needle biopsies positive for carcinoma in this period were included. Prostate-specific antigen levels were available in 60.8% cases and ranged from 5.0 to 1747 ng/mL. Tumor was bilaterally present in 54.6% cases. Tumor positivity in right apex, mid, and base was 52.6%, 54.6%, and 51.5%, respectively. Tumor positivity in left apex, mid, and base was 55.7%, 63.9%, and 59.8%, respectively. Average tumor volume in right apex, mid, and base was 51.2%, 50.6%, and 49.9%, respectively. Average tumor volume in left apex, mid, and base was 49.8%, 49.1%, and 51.6%, respectively. Gleason score was 6 in 52.6% cases and 7 in 28.9% cases. Perineural invasion was positive in 46.4% cases. High-grade prostatic intraepithelial neoplasia was seen in 4 (4.1%) of 97 cases. On statistical analysis, no significant correlation was found between tumor volume and serum PSA levels. However, significant correlation was found between tumor volume and Gleason grade and between tumor volume and presence of perineural invasion. No significant correlation was found between Gleason grade and serum PSA level. To our knowledge, these are the first reported findings in prostatic needle biopsies from Pakistan. Most prostatic carcinomas in our country are still diagnosed on transurethral resection specimens, and needle biopsies are quite uncommon. Findings in needle biopsies will help in predicting adverse prognostic factors on radical prostatectomies and in planning surgery accordingly.

[Benign mimickers of the prostate cancer. Diagnostic challenges]. / Lésions bénignes mimant le cancer de la prostate. Challenges diagnostiques.

The diagnosis of prostate cancer (PCa), especially limited adenocarcinoma on needle biopsy, is often challenging. Before making diagnosis of PCa, it is prudent for the pathologist to consider different benign patterns that may lead to a false positive interpretation. Histoanatomic structures such as seminal vesicles, Cowper's glands and paraganglia along with hyperplasia, atrophy with its different patterns and adenosis may generate difficulties in differential diagnosis. Furthermore, inflammatory processes and post-treatment changes may cause problems. The above entities can in some instances simulate low-grade and less commonly high grade PCa. Knowledge of these patterns and application of appropriate immunohistochemistry will lead the pathologist to a correct diagnosis.

Diagnosis of limited adenocarcinoma of the prostate.

This article provides an overview of the diagnosis of limited prostate cancer on needle biopsy. A few of the more common mimickers of prostate cancer, such as adenosis, partial atrophy, and high-grade prostatic intraepithelial neoplasia, are also covered. A systematic approach to diagnosing prostate cancer by evaluating architectural, nuclear, intraluminal and ancillary features is presented. The use of immunohistochemistry, including its pitfalls and limitations, is described and illustrated. By the use of a systematic diagnostic approach as outlined in this article, the threshold for diagnosing limited carcinoma of the prostate can be decreased. If a pathologist is not comfortable in diagnosing carcinoma in a particular small focus, this review will help them to recognize these foci as atypical and suspicious for carcinoma, so that further workup might lead to a more definitive diagnosis. Some of the more common situations leading to an atypical diagnosis have also been presented to help prevent the overdiagnosis of prostatic malignancy.