High-grade Prostate Carcinoma Research Articles

Prostate volume predicts high grade prostate cancer both in digital rectal examination negative (ct1c) and positive (≥ct2) patients.

We aimed to assess the relationship between prostate volume (PV) and high grade prostate carcinoma (HGPCa) in patients with benign and suspicious digital rectal examination (DRE) in our prostate biopsy cohort. Between 2009-2012, 759 consecutive initial transrectal systematic 12 cores prostate biopsies were included. PVs were calculated with transrectal ultrasound. Only prostate adenocarcinomas (PCa) were included into the study. For standardization, patients with missing data, and who have been exposed to any form of hormonal or radiation therapy were excluded. Patients were categorized with DRE (negative or positive) and Gleason sum [<7: low grade PCa(LGPCa), ≥7: HGPCa]. Median PV was significantly lower in patients with HGPCa. There was a significantly increased risk of HGPCa with PV according to all groups in univariate logistic regression (LR). The significant relationship continued in multivariate LR with PSA and age. From the ROC curve analyses, again a significantly statistical concordance was found between the detection of HGPCa and PV (AUC:0.63, p<0.001), as well as between HGPCa and tPSA (AUC:0.73, p<0.001). tPSA and PV were also significantly concordant with HGPCa both in DRE negative and positive patients. There is a significant relationship between HGPCa and decreasing PV. The continued significant relationship both in DRE negative and positive patients reinforces this relation.

High-Grade Prostatic Intraepithelial Neoplasia and Intraductal Carcinoma With Intraluminal Small Cell Features

High-Grade Prostatic Intraepithelial Neoplasia and Intraductal Carcinoma With Intraluminal Small Cell Features

Prostate ductal adenocarcinoma metastatic to the brain: case reports and pitfalls in immunohistochemical interpretation

Prostate cancer is the most common cancer in Australian men and pure ductal adenocarcinoma of the prostate (DAP) constitutes 1 % of the cases. While DAP was initially thought to behave more indolently than acinar-type prostatic adenocarcinoma, it is now regarded as more aggressive, with a greater propensity to metastasise. There is however a paucity of literature relating to brain metastasis by the tumour. We report two cases of metastatic DAP to the brain which showed some positivity for CK7 and CK20 while negative and/or only focally positive for PSA and PSAP. The case reports also highlight a potential diagnostic pitfall in immunohistochemical interpretation of high grade prostate carcinomas with these four traditional antibodies. Pure prostate ductal adenocarcinoma, which by definition is Gleason score 4 + 4 = 8, may easily be overlooked in the differential diagnosis of metastatic brain tumours with cribriform, papillary, solid and/or complex glandular architecture if the immunohistochemistry is also misinterpreted.

Incidence and clinicopathological characteristics of intraductal carcinoma detected in prostate biopsies: a prospective cohort study

Intraductal carcinoma of the prostate (IDC-P) is a distinct clinicopathological entity and is associated with aggressive, high-grade and high-volume prostate carcinoma (PCa). The incidence, clinicopathological characteristics and prognostic significance of IDC-P have not been reported in prostate biopsies (PBx) that surgical pathologists encounter in their daily practice. In 1176 prospectively collected PBx, 33 IDC-P cases were identified (2.8%). The mean age of patients with IDC-P was 65 (range 46-79) years and mean serum prostate-specific antigen was 16.2 (range 0.4-105.6) ng/ml. Three (0.26%) IDC-P cases did not have a concomitant invasive PCa. Of 30 cases with concomitant invasive PCa, Gleason score was 7 in 16 (53.3%), 8 in four (13.3%) and 9 in 10 (33.3%) cases. The mean number of biopsy cores involved by PCa was 7.2 (range 1-14). Nine patients were treated with radical prostatectomy. Seminal vesicle invasion was found in four of nine (44%) cases, significantly higher than the risk of 12% predicted by Partin Tables (P = 0.016). This is the first prospective study that has investigated the incidence and prognostic significance of IDC-P diagnosed in PBx encountered in daily practice. It is critical for surgical pathologists to diagnose and report IDC-P in PBx.

Prostate MRI: Who, when, and how? Report from a UK consensus meeting

The current pathway for men suspected of having prostate cancer [transrectal biopsy, followed in some cases by magnetic resonance imaging (MRI) for staging] results in over-diagnosis of insignificant tumours, and systematically misses disease in the anterior prostate. Multiparametric MRI has the potential to change this pathway, and if performed before biopsy, might enable the exclusion of significant disease in some men without biopsy, targeted biopsy in others, and improvements in the performance of active surveillance. For the potential benefits to be realized, the setting of standards is vital. This article summarizes the outcome of a meeting of UK radiologists, at which a consensus was achieved on (1) the indications for MRI, (2) the conduct of the scan, (3) a method and template for reporting, and (4) minimum standards for radiologists.

Diagnostic utility of androgen receptor expression in discriminating poorly differentiated urothelial and prostate carcinoma

AimsPathological separation of poorly differentiated urothelial and prostate carcinoma is difficult, but imperative because of the impact on patient management. Tumour morphology, in conjunction with a panel of immunohistochemistry (IHC),...

Immunohistochemical Analysis of the Extrinsic Apoptosis Process in the Non-Neoplastic and Neoplastic Prostate.

Deviations in the apoptotic process have been demonstrated in prostate carcinogenesis. We aimed to evaluate especially the process of extrinsic apoptosis in the spectrum of neoplastic lesions of the prostate epithelium so as to reveal the variations in the apoptotic process. The study included 20 benign prostatic hyperplasia, 8 high-grade prostatic intraepithelial neoplasia and 82 prostatic carcinoma patients. Immunohistochemistry was performed on sections obtained from materials of suprapubic prostatectomy, tru-cut biopsy, transurethral resection and radical prostatectomy. While Fas and FasL were evaluated in glandular and stromal areas, DcR1 and FLIP were evaluated in only glandular areas. Intensity and extent of immunostaining for Fas and FasL antibodies were separately scored and both scores were summarized. The total score of ≥ 4 both for Fas and FasL, expressions of FLIP and DcR1determined in more than 5% of glandular areas were accepted as positive. Glandular FasL positivity was observed in 63.8 and 20% of the cases with prostatic carcinoma and benign prostatic hyperplasia, respectively (p=0.001). The loss of stromal Fas expression in PCa was obvious (p < 0.001). FLIP positivity was more frequently seen in high-grade prostatic intraepithelial neoplasia and PCa. In prostatic carcinoma, decreased stromal Fas expression, contrary to higher glandular FasL positivity, supports the assertion that sensitivity of epithelial and stromal cells to apoptosis and their protective pathways against apoptosis undergo alterations. Increased FLIP expressions in high-grade prostatic intraepithelial neoplasia and prostatic carcinoma can also be interpreted accordingly.

Small cell–like change in prostatic intraepithelial neoplasia, intraductal carcinoma, and invasive prostatic carcinoma: a study of 7 cases

Small cell carcinoma of the prostate is associated with poor prognosis and different treatment from conventional acinar adenocarcinoma. Given the important clinicopathologic implications of a diagnosis of small cell carcinoma, we report 7 cases showing unusual, extensive small cell-like change in intraductal carcinoma and invasive carcinoma. Prostatic biopsies from 3 patients and radical prostatectomy specimens from 4 patients showed variably extensive small cell-like high-grade prostatic intraepithelial neoplasia and intraductal carcinoma. Five cases were associated with conventional acinar adenocarcinoma (2 cases with Gleason score 4 + 3 = 7; 3 cases with Gleason 3 + 4 = 7). No small cell carcinoma was seen. Small and large ducts with small cell-like change showed solid and cribriform proliferations of atypical cells with abrupt transition between centrally located populations of small cells and more typical large dysplastic cells at the duct periphery. Rosette-like formations were noted within some involved ducts. Small cell-like change was characterized by crowded cells with uniformly bland vesicular nuclei and minimal cytoplasm and no significant mitotic or apoptotic activity. In 3 cases, similar small cell-like morphology was noted focally in invasive carcinoma. The small cell-like areas were negative for synaptophysin and chromogranin, focally positive for TTF-1, and weakly positive for racemase. Ki-67 labeled less than 5% with predominant labeling of the larger atypical cells and minimal reactivity in the small cell-like population. In summary, small cell-like change in prostatic intraepithelial neoplasia, intraductal carcinoma, and invasive carcinoma is not associated with small cell carcinoma; shows no immunohistochemical evidence of neuroendocrine differentiation; and likely is not an adverse prognostic feature.

Effect of zinc(II) ions on the expression of pro- and anti-apoptotic factors in high-grade prostate carcinoma cells

Several typical characteristics of prostate tissue have been identified including the ability to accumulate zinc(II). However, this feature of prostate cells is lost during carcinogenesis and, thus, prostate cells are unable to accumulate zinc(II) ions in high levels. Therefore, we can expect that zinc(II) ions can significantly contribute to the progression of tumour disease and to the ability of prostate cell lines to metastasize. In this study, we aimed our attention on determining the expression of Bcl-2, c-Fos, c-Jun, Ki-67, NF-κB and p53 genes in two prostate cell lines, as the 22Rv1 cell line, a model of aggressive partially androgen-sensitive prostate cancer and the PNT1A cell line, a normal prostate cell line model. Moreover, we were interested in the mechanisms through which exposure of these cell lines to zinc(II) ions could influence expression of the above-mentioned genes. We found that zinc(II) ions caused elevated expression of Ki-67, a marker of proliferation, extremely low expression of p53, high expression of Bcl-2 and no changes in the expression of p53. Our experimental data show different effect of zinc(II) ions on expression of the above-mentioned regulatory genes, which may give us more information on their impact on cancer development and progression with possible using for cancer therapy.

Initial Experience With Identifying High-Grade Prostate Cancer Using Diffusion-Weighted MR Imaging (DWI) in Patients With a Gleason Score ≤3 + 3 = 6 Upon Schematic TRUS-Guided Biopsy

Diffusion-weighted magnetic resonance (MR) imaging (DWI) might be able to fulfill the need to accurately identify high-grade prostate carcinoma, in patients initially selected for active surveillance in the Prostate Specific Antigen (PSA) screening era based on transrectal ultrasound-guided biopsy Gleason score. We aimed to determine whether DWI is able to correctly identify those patients with a biopsy Gleason score of ≤ 3 + 3 = 6, but harboring Gleason 4 and/or 5 components in their radical prostatectomy (RP) specimen. Whole-mount RP specimens were used to identify regions of interest corresponding with tumor on the DWI-derived apparent diffusion coefficient (ADC) maps in 23 patients with a Gleason ≤ 3 + 3 = 6 on biopsy. ADC values were correlated with RP Gleason grades. Statistical analysis was performed by calculating area under the receiver operating characteristic curve for identification of prostate cancer with Gleason 4 and/or 5 components using DWI, and Mann-Whitney U testing was performed to detect differences in median ADC values for tumors with presence of Gleason grade 4 and/or 5 versus a highest Gleason grade of ≤ 3 on RP. A diagnostic accuracy of median ADC values for identifying patients subject to transrectal ultrasound-guided biopsy undergrading with an area under the receiver operating characteristic curve of 0.88 was established using RP Gleason score as a reference. In patients harboring a Gleason 4 and/or 5 component, the median ADC was 0.86 × 10(-3) mm/s (standard deviation ± 0.21), whereas patients harboring no Gleason 4 and/or 5 component displayed a median ADC of 1.16 × 10(-3) mm/s (standard deviation ± 0.19) for the single tumor slice with the lowest median ADC (P < 0.002). DWI is able to predict the presence of high-grade tumor in patients with a Gleason ≤ 3 + 3 = 6 on biopsy, providing important information for treatment decisions.

Gene expression profiles and differential cytoglobin expression in atrophy and adenocarcinoma of the prostate

Proliferative inflammatory atrophy (PIA) has been proposed as a potential precursor for prostate cancer. The precise molecular abnormalities in prostatic atrophy compared to high-grade prostatic intraepithelial neoplasia (HGPIN) and carcinoma have not been fully defined. We utilized laser capture microdissection and microarray analysis to characterize cells of PIA, HGPIN, invasive prostatic carcinoma, and non-atrophic benign prostatic epithelium (NABE). Cytoglobin was selected for immunohistochemistry (IHC) validation. IHC stains were evaluated for proportion of positive glands, and intensity of cytoglobin staining. An immunoreactive score (IR score) was determined as the product of the percentage of positive staining and intensity. Microarray analysis revealed probe sets that separated the microdissected cell types. Several genes showed overlapping expression patterns between PIA and PIN, and HGPIN and invasive carcinoma. Cytoglobin protein expression was detected in 57/93 (61%) of NABE and BPH cases, 92/93 atrophy (99%), 3/34 (9%) of PIN, and 23/61 carcinoma (37%) samples. The highest IHC scores were calculated for atrophy foci. A subset (33%) of atrophy cases showed the same low-cytoglobin expression level as PIN and carcinoma. Prostatic epithelium can be stratified into normal, atrophic, PIN, and invasive carcinoma categories based on differential genetic signatures. Cytoglobin, a protein that can be induced in response to oxidative stress, was elevated in most atrophy foci, suggesting hypoxic, and/or oxidative damage. The lower level of cytoglobin seen in neoplastic cells and 33% of atrophy foci may indicate a shared susceptibility to oxidative damage for this subset of atrophy cases and prostatic neoplasia.

Prostatic atrophy: clinicopathological significance

Prostatic atrophy is a benign lesion that may mimic adenocarcinoma histologically and on imaging. It is more frequent in the peripheral zone and has gained importance with the increasing use of needle biopsies. Diffuse atrophy occurs secondarily to radiotherapy and/or endocrine therapy. Inflammation and/or chronic local ischemia may cause focal atrophy with an increasing frequency in age. Atrophy may be classified morphologically into diffuse and focal. The latter may be partial, complete or combined. Partial focal atrophy is the most frequent mimicker of adenocarcinoma on needle biopsies. Complete focal atrophy may be subtyped into simple, sclerotic and hyperplastic (or postatrophic hyperplasia). Combined lesions are frequent and partial atrophy may precede complete atrophy. The several morphologic types of focal atrophy may represent a morphologic continuum and the hyperplastic (or postatrophic hyperplasia) subtype seems to be at the extreme end of this continuum. Chronic inflammation associated to focal atrophy (proliferative inflammatory atrophy) has been linked to high-grade prostatic intraepithelial neoplasia and/or carcinoma. This link, however, remains controversial in the literature. The question whether inflammation directly produces tissue damage and atrophy or some other insult induces atrophy directly, with inflammation occurring secondarily, is still unresolved. An intriguing finding that needs further studies is a possible association of extent of atrophy to serum PSA elevation.

Abstract 3995: Differential expression of CD10 immunohistochemistry in stroma and epithelium of prostatic adenocarcinoma

Abstract Introduction: CD10 is a transmembrane metallo-endopeptidase involved in cleavage and inactivation of certain peptide hormones important for signal transduction. CD10 is strongly expressed by normal prostatic luminal epithelial cells. Immunohistochemical (IHC) studies have shown expression of CD10 in prostatic adenocarcinoma. (PCa). Loss of CD10 expression is a common, early event in human prostate cancer (PCa); however, CD10 positive cancer cells frequently appear in lymph node metastasis. Only a few studies are available on the expression of CD10 in the prostatic stromal and cancer cells. We investigated the IHC expression of CD10 in epithelium and stroma of PCa using TMAs. Material and Methods: Prostate tissue from 72 radical prostatectomies was used to construct two TMAs; 35 case of Gleason score (GS) 6(3+3) and 37 cases of high grade (HG) prostate cancer (GS 8, 9, 10) were included. Each case was represented by three, 1mm cores for a total of 105 cores for the GS6 and 111 cores for HG prostate carcinomas. TMAs were stained with H&amp;E and IHC was performed for CD10. Digital images of the TMA slides were scanned using the T3 ScanScope by Aperio Technologies. Epithelial and stromal expression of CD10 was scored as negative or positive. Results: CD10 was expressed in epithelium and stroma of PCa. CD10 had heterogeneous expression within individual patients in both epithelium and stroma. This heterogeneity was not significantly different between GS6 and HG prostate cancer. CD10 was differentially expressed in epithelium of GS6 and HG prostate cancer. HG prostate cancer showed significantly more epithelial staining with CD10 (p=0.001) and less stromal staining with CD10 (p=0.003) compared to GS6. Conclusion: GS6 and HG prostate cancer demonstrate a reverse relationship between CD10 expression in the epithelium and the stroma. Epithelial CD10 expression is an unfavorable risk factor in prostate cancer. Prostate tumors expressing high levels of epithelial CD10 correlate with a poor disease outcome. CD10 may be important in the biology of the tumor stromal microenvironment and its contribution to tumor progression requires further investigation. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3995.

Atypical Cribriform Lesions of the Prostate: Relationship to Prostatic Carcinoma and Implication for Diagnosis in Prostate Biopsies

Atypical cribriform lesions of the prostate (ACL) are cribriform glands lined by cytologically malignant cells with partial or complete basal cell lining. They represent cribriform high-grade PIN (cribriform HGPIN), which can be an isolated finding not associated with PCa (isolated ACL), or "intraductal carcinoma (IDC-P)" that is almost always associated with infiltrative high-grade prostate carcinoma (PCa) (cancer-associated ACL, ACL-PCa). We report the incidence, topographic relation to cancer, and morphologic differences of these 2 lesions in radical prostatectomy and discuss the potential biologic basis and implication for diagnosis in prostate biopsy. ACL was defined as cribriform glands comprising cytologically malignant cells that spanned the entire glandular lumens with partial or complete basal cell lining confirmed by basal cell immunostaining. ACL intermixed with, or within 3 mm from the border of infiltrative PCa was categorized as ACL-PCa and was considered to be equivalent to IDC-P. ACLs other than ACL-PCa were considered as isolated ACL and equivalent to cribriform HGPIN. These histologic features of ACL were reviewed: number of ACL/prostate gland, size, glandular contour (round, irregular, branching), architectural pattern (dense cribriform, irregular cribriform, solid), comedonecrosis, and nuclear features (round and uniform, round with varying sizes, pleomorphic, giant nuclei [6x adjacent nuclei]). In 117 consecutive radical prostatectomy specimens, ACL-PCa and isolated ACLs were found in 21 (17.9%) and 15 (12.8%), respectively. ACL-PCa was more common in PCa with Gleason score more than or equal to 7 and higher tumor volume. The isolated ACLs were more common in Gleason score 6 PCa and their incidence was not significantly different among PCa with different tumor volumes. The mean number of ACL per prostate was 23.8 for ACL-PCa and 2.4 for isolated ACL (P=0.008). The size ranged from 0.2 to 9.0 mm for ACL-PCa, and from 0.2 to 1 mm for isolated ACL. The branching contour was present in 36/43 ACL-PCa, but only in 1/23 isolated ACL (P<0.001). The dense cribriform and solid architecture were present in 6 (14.0%) and 4 (9.3%) of ACL-PCa, but none of the isolated ACLs. Comedonecrosis was present in 14/43 (32.6%) ACL-PCa, and in none of the isolated ACL (P=0.001). The pleomorphic nuclei or giant nuclei at least 6X of the adjacent nuclei, were present in 12 (27.9%) ACL-PCa, but in none of the isolated ACL (P=0.005). ACL can be found both in association with PCa or without associated infiltrative PCa. Isolated ACL is uncommon, and the overwhelming majority of ACLs is associated with high grade (GS> or =7) and high-volume PCa and represents IDC-P. Large gland size (>1 mm), large focus involving many glands (number>6), complex architecture, and high-grade nuclei are characteristic of IDC-P. However, cribriform HGPIN and IDC-P overlap at the "low grade" architectural and morphologic spectrum and are difficult to distinguish based on morphologic criteria alone. If a biopsy contains a small number of ACL glands with "low grade" morphology, it should be diagnosed as "atypical cribriform lesion, cannot distinguish between cribriform HGPIN and IDC-P" and a repeat biopsy should be strongly recommended to rule out unsampled PCa. In contrast, if a biopsy contains ACL with one or several features of large focus, architectural complexity with large branching glands, pleomorphic or giant nuclei, or comedonecrosis, the biopsy should be diagnosed as IDC-P and definitive therapy should be recommended.

Prostatic diseases in the senescence: structural and proliferative features

Senescence is one of the main aetiological factors which are responsible for natural androgen ablation in men and occurrence of prostatic diseases. However, it is unclear how the prostatic lesions are signallised in the prostate. Thus, the aim of this study is to characterise the structural, the ultrastructural and the proliferative aspects of the peripheral prostatic zone in the elderly men with and without diagnoses of prostatic lesions and with potential precursors of prostate cancer. Sixty samples of prostatic tissue, from 60 to 90-year-old patients with and without lesions obtained from autopsied or prostatectomised patients were divided into four groups (15 samples per group): standard group (no lesions), benign prostatic hyper-plasia group, high-grade prostatic intra-epithelial neoplasia group and prostatic carcinoma group. The samples were submitted to morphometrical, structural and ultrastructural analyses in addition to cellular apoptosis and proliferative analyses. The results showed morphological damages in the stroma and cellular organelles involved in the secretory process of the prostate. Moreover, the prostatic lesions in elderly men demonstrated disturbance in the proliferation/apoptosis rate, indicating a prevalence of the proliferative process. Finally, the imbalance in prostatic stroma-epithelium interaction was a harmful feature in the elderly men as a result of structural changes, which are crucial factors for the development and progression of carcinogenesis.

Association of CASP8 D302H polymorphism with reduced risk of aggressive prostate carcinoma.

Because of the dramatically different clinical course of aggressive and indolent prostate carcinoma (PCa), markers that distinguish between these phenotypes are of critical importance. Apoptosis is an important protective mechanism for unrestrained cellular growth and metastasis. Therefore, dysfunction in this pathway is a key step in cancer progression. As such, genetic variants in apoptosis genes are potential markers of aggressive PCa. Recent work in breast carcinoma has implicated the histidine variant of CASP8 D302H (rs1045485) as a protective risk allele. We tested the hypothesis that the H variant was protective for aggressive PCa in a pooled analysis of 796 aggressive cases and 2,060 controls. The H allele was associated with a reduced risk of aggressive PCa (OR(per allele) = 0.67, 95% CI: 0.54-0.83, P(trend) = 0.0003). The results were similar for European-Americans (OR(per allele) = 0.68; 95% CI: 0.54-0.86) and African-Americans (OR(per allele) = 0.61; 95% CI: 0.34-1.10). We further determined from the full series of 1,160 cases and 1,166 controls in the Prostate, Lung, Colorectal, Ovarian (PLCO) population that the protective effect of the H allele tended to be limited to high-grade and advanced PCa (all cases OR(per allele) = 0.94; 95% CI: 0.79-1.11; localized, low-grade disease OR(per allele) = 0.98; 95% CI: 0.79-1.23; and aggressive disease OR(per allele) = 0.73; 95% CI: 0.50-1.07). These results suggest that histidine variant of CASP8 D302H is a protective allele for aggressive PCa with potential utility for identification of patients at differential risk for this clinically significant phenotype.

Combined magnetic resonance imaging and spectroscopy in the assessment of high grade prostate carcinoma in patients with elevated PSA: A single-institution experience of 356 patients

Purpose To assess the ability of combined whole-prostate magnetic resonance imaging and magnetic resonance spectroscopy imaging (MRI + MRSI) to predict the presence or absence of high grade (Gleason 4 + 3 or higher) prostate carcinoma in men with elevated PSA. Materials and methods Between March 2002 and September 2007, 356 subjects (mean serum PSA 11.5 ng/ml, range 0.4–133.0 ng/ml) were examined with fast-T2-weighted magnetic resonance imaging (MRI) and 3D-magnetic resonance spectroscopy imaging (MRSI) on a 1.5 T scanner. Prostate cancer was histopathologically proven in 220 patients (41 with high grade and 179 with lower grade cancer) and non-evidence of cancer was determined after at least 12 months (mean 21 months) clinical follow-up in 136 subjects. The sensitivity, false positive rate, and negative predictive value of MRI + MRSI were calculated using histopathology and follow-up results as reference standard. Results MRI + MRSI had a significantly higher sensitivity for high grade tumors (92.7%) than for lower grade tumors (67.6%), and was false positive in only 7.4% of patients with non-evidence of prostate cancer. For exclusion of a high grade tumor, MRI + MRSI had a negative predictive value of 98.4%. Conclusions MRI + MRSI holds great potential for predicting presence or absence of high grade tumors in men with elevated PSA. This can be important in the selection of patients for active surveillance, or in the decision to rebiopsy patients with prior negative biopsies.

Clinical and pathologic characteristics of primary prostatic signet ring cell carcinoma

Objective To discuss the clinicopathologic features, diagnosis and treatment of pri-mary prostatic signet ring cell carcinoma (PPSRCC). Methods Clinical data of 23 PPSRCC cases were retrospectively reviewed. The mean age was 74 years and majority of them had aggravated dysu-ria. The mean serum PSA was 45.3 ng/ml (7.4-126.8 ng/ml). To exclude the metastasis from stomach and colon SRCC, upper gastric tract endoscopy and barium enema were carried out. Seven pa-tients received radical prostatectomies and 2 patients who had positive margins received hormonal and radiation therapy. The rest of patients received maximal androgen blockade therapy. Photoselective vaporization of the prostate was performed on 11 patients who had lower urinary tract symptoms. All cases were investigated by routine pathological, immunohistochemical studies. Results Seventeen cases of PPSRCC were associated with concurrent high-grade prostatic carcinoma, only 6 cases were pure SRCC. Immunohistochemical stains were positive in all cases for PSA and PAP. Stains were ne-gative for AB/PAS (23/23) and CEA (21/23). The clinical TNM stages were 7 of Ⅱ , 10 of Ⅲ and 6 of Ⅳ. Follow-up was available on 20 cases with a mean 24 months and 3 cases were lost during follow up. Eight cases died of metastasis. Five cases had evidence of recurrence 12-21 months from presen-tation. Conclusions The diagnosis of PPSRCC depends on pathological and immunohistochemical studys after metastasis from stomach and colon SRCC is excluded. Early diagnosis and combination treatment for PPSRCC might improve its prognosis. Key words: Prostatic neoplasms; Carcinoma; Signet ring cell

CD4+ lymphocytes modulate prostate cancer progression in mice

Chronic inflammation contributes to the development of prostate cancer in humans. Here, we show that male Apc(Min/+) mice also develop prostate carcinoma with increasing age, mimicking that seen in humans in their 5th or 6th decade of life. Proinflammatory cytokines were significantly linked with cancer and increasing age in our mouse model; however, prostate and bowel tissues lacked evidence of inflammatory cell infiltrates other than mast cells. Lymphocytes protected against cancer, and protection from prostate cancer resided in antiinflammatory CD4(+)CD25(+) regulatory (T(REG)) cells that downregulated inflammatory cytokines. Supplementation with syngeneic T(REG) cells collected from wild-type mice reduced the levels of interleukin (IL)-6 (p < 0.05) and IL-9 (p < 0.001) and lowered prostate cancer risk (p < 0.05). Depletion of CD25(+) cells in 2-month-old animals increased the expression of IL-6 (p < 0.005) within prostate and increased the frequency of high-grade prostatic intraepithelial neoplasia (p < 0.05) and microinvasive prostatic carcinoma (p < 0.05) in dorsolateral prostate. Depletion of CD25(+) cells in young animals also increased the frequency of intestinal cancer in Min mice. Taken together, chronically elevated proinflammatory cytokines promoted carcinoma in Apc(Min/+) mice. T(REG) lymphocytes downregulated inflammation-associated carcinogenic processes and contributed to immune and epithelial homeostasis.

α‐Methylacyl‐CoA racemase (AMACR) in fine‐needle aspiration specimens of prostate lesions

The elevated expression of P504S gene and its product alpha-methylacyl-CoA racemase (AMACR) can serve as a molecular marker for prostate cancer. The goal of this study is to investigate P504S/AMACR expression in fine-needle aspiration smears and correlate it with cytological diagnosis. Immunocytochemistry was performed in 35 patients with morphological diagnosis of prostate carcinoma (n = 16), atypia (n = 15), and benign hyperplasia (n = 4). Among 16 malignant cases there were two low-grade, eight intermediate, and six high-grade prostate carcinomas. Cytoplasmic positivity is analyzed qualitatively as predominantly diffuse or focal and quantitatively as <5%, 5-50%, and >50% of cells. Benign cases showed no P504S/AMACR expression. Positive staining was recorded in 75% of malignant cases, but in the majority of them it was weak and focal or diffuse and in a small amount of cells. The most intensive staining was seen in low-grade carcinomas and some atypical cases. This observation indicates a correlation between P504S/AMACR expression and differentiation of cells. P504S/AMACR staining might be of great value in cytodiagnosis of prostate lesions as well as an example of the characterization of cells at the molecular level using fresh tissue obtained by fine-needle aspiration.