Cancer volume and site of origin of adenocarcinoma in the prostate: relationship to local and distant spread.

Biologic aggressive behavior in adenocarcinoma of the prostate is proposed to be a direct function of cancer volume. In an autopsy series, distant metastasis was found only in cancers that had both volume greater than 5 cc and areas of poor differentiation (Gleason grades 4 and 5). In subsequent study of over 200 radical prostatectomy specimens, cancers were found to originate both in the peripheral zone (PZ) and in the normally small anteromedial transition zone (TZ) where benign nodular hyperplasia also develops. Anatomic TZ and PZ cancers were nearly equivalent to clinical stage A and B cancers, respectively. Transition zone cancers showed much less capsule penetration and seminal vesicle invasion than PZ cancers of comparable volume because the TZ boundary provided a barrier to cancer spread through the PZ. In PZ carcinomas, capsule penetration depended largely on facilitated spread along perineural spaces, and its distribution was determined by the location of superior and inferior nerve pedicles. Capsule penetration, seminal vesicle invasion, and positive surgical margins were all strongly correlated with cancer volume. Tumors smaller than 4 cc had all morphologic variables favorable; tumors larger than 12 cc tended to have all variables unfavorable. Lymph node metastasis in radical prostatectomy cases was most strongly predicted by a combination of cancer volume plus percentage of high-grade tumor. Cancers with more than 3.2 cc of grade 4 and/or 5 component showed a 100-fold increase in proportion of cases with nodal spread.     

Discrepancies between Gleason scores of needle biopsy and radical prostatectomy specimens

The purpose of this study was to determine the accuracy of Gleason scores in prostate needle biopsy diagnosis and to investigate factors affecting the accuracy of the tumor grade. A single pathologist reviewed 116 sets of prostate cancer biopsies and radical prostatectomy specimens. The following factors were examined to determine their effect on the accuracy of the biopsy Gleason scores: (i) relative tumor differentiation; (ii) pathological stage; (iii) amount of tissue in the biopsy specimen; (iv) amount of cancer tissue in the biopsy specimen; (v) tumor heterogeneity; (vi) clinical findings (prostate specific antigen value and digital rectal examination); and (vii) interobserver variability. In 53 cases the Gleason score of biopsy specimens was identical to the score of prostatectomy specimens (45.7%). Fifty-four cases (46.6%) of biopsy specimens were undergraded. The most common discrepancy was diagnosis of well-differentiated carcinoma in the biopsy but diagnosis of moderately differentiated tumor in the corresponding prostatectomy specimen. This discrepancy occurred when the amount of tumor in the biopsy was 3 mm or less. Biopsy and prostatectomy results showed less agreement when the original biopsy tumor grade rendered by nine different pathologists was used, suggesting that interobserver variability can adversely affect the accuracy of tumor grade. Clarifying the histologic criteria for distinguishing each grade, especially between Gleason grades 2 and 3, is important for accurate grading.     

Alpha-methylacyl-CoA racemase (P504S) expression in evolving carcinomas within benign prostatic hyperplasia and in cancers of the transition zone

Carcinomas of the transition zone (TZ) constitute approximately 20% of all prostate cancers. The TZ is the site of origin of grade 1 and grade 2 cancers, the most well-differentiated of the Gleason grade tumors, as well as for benign prostatic hyperplasia (BPH). In this regard, grade 1 carcinoma has architectural features that closely mimic gland-rich BPH nodules. Although a relationship between cancers arising in this zone and BPH has been suspected, such an association remains undefined. To gain insight into the origin, development, and progression of cancers arising in the TZ, we used a highly specific rabbit monoclonal antibody (P504S) directed against alpha-methylacyl-CoA racemase (AMACR) to study the expression of the enzyme in 25 cases of evolving and fully developed carcinomas of this zone. AMACR has been proposed as a new molecular marker for prostate cancer, because the enzyme is reportedly overexpressed in high-grade dysplasias, also termed prostatic intraepithelial neoplasia, a purported precursor of prostatic carcinoma, and in all grades of prostatic carcinoma of the peripheral zone. Using P504S, P63, or antikeratin 34beta E12 antibodies, we found it possible to define areas of transition from hyperplasia to carcinoma in 6 BPH nodules. In 3 other cancer-containing BPH nodules, staining for AMCAR was observed in benign hyperplastic glands that were juxtaposed to carcinoma. Enzyme expression was also evident in 5 additional cases in which BPH was found adjacent to cancer. In contrast; AMACR was not visualized in any other BPH nodules that we studied. Thus, using the enzyme as a marker, we document for the first time that some carcinomas of the TZ arise from an AMCAR-positive transition lesion within a subset of BPH nodules. Moreover, the finding of enhanced AMACR expression in benign glands within cancer-containing nodules as well as in BPH lesions adjacent to carcinoma suggests that in some cases, up-regulation of the enzyme may precede morphological evidence of neoplastic transformation. AMACR was lightly expressed in transition lesions and grade 1 carcinomas but more strongly expressed in higher-grade TZ cancers, suggesting that enzyme expression is enhanced with progression in this zone. Because AMACR is involved in the beta oxidation of branched fatty acids and their derivatives, enhanced expression of the enzyme in evolving carcinomas in BPH nodules, as well as its up-regulation in juxtaposed morphologically benign glands and grade 1 carcinomas, suggests that increased utilization of fatty acids may play an important role in carcinoma development and progression in the TZ.     

Ki-67 expression in early prostate cancer and associated pathological lesions.

AIM: To assess cell proliferation in early prostate cancer and associated pathological lesions. METHODS: Using the Ki-67 antibody, the cell proliferation index was measured in early stage prostatic carcinoma in 37 incidental tumours diagnosed at transurethral prostatectomy (TURP) and in 20 low volume cancers treated by radical prostatectomy. Proliferation indexes have also been measured in areas of normal peripheral zone, transition zone hyperplasia, atrophic appearing lobules, and high grade prostatic intraepithelial neoplasia in the radical prostatectomy cases. RESULTS: In the TURP series the proliferation index correlated with grade and stage. Logistic regression analysis, however, showed that Gleason grade was the most reliable predictor of biopsy proven residual disease and clinical progression. In the radical series transition zone carcinoma the proliferation index was half that of peripheral zone carcinoma. The atrophic lobules also showed a high proliferation index of the same order as seen in the peripheral zone carcinoma. Normal peripheral zone showed the lowest proliferation index and in hyperplastic transition zone it was also less than the other areas. CONCLUSIONS: There is only limited support for the correlation of proliferation index with grade in early stage prostatic carcinoma. The findings do not suggest that proliferation index adds to the prognostic information given by grade and stage in pT1 disease. The significant difference in proliferation index in transition zone and peripheral zone carcinomas supports the morphological distinction of these tumour types and is consistent with differences in biological behaviour. The high proliferation index in lobules considered morphologically atrophic is reminiscent of previous observations in which carcinoma was spatially associated with atrophy.     

Diagnosis and localization of prostate carcinoma by fine-needle aspiration cytology and correlation with histologic whole-organ sections after radical prostatectomy

Twenty-nine patients with clinical stage T1-2, NO, MO prostate carcinoma were treated by retropubic radical prostatectomy. Diagnosis was made by fine-needle aspiration biopsy from six to eight separate sectors of the prostate. At the time of biopsy, diagrams of the palpated organ were drawn, depicting the location of the lesion and the site of each biopsy. Without the examiners' knowledge of cytologic data, extirpated prostate glands were examined with whole organ histologic sections, and carcinomas were scored according to the method of Gleason. The location and extent of all typical and malignant foci were mapped on a standard diagram. The results of preoperative cytologic examination were compared with postoperative histopathologic findings, showing a tendency toward underestimation of both the extent and degree of differentiation of the carcinomas during cytologic examination. In no case were these parameters overestimated during cytologic examination. The Gleason score correlated well with the presence of capsular and seminal vesicle invasion.     

HISTOLOGICAL GRADE HETEROGENEITY IN MULTIFOCAL PROSTATE CANCER. BIOLOGICAL AND CLINICAL IMPLICATIONS

In order to understand the clinical and biological implications of prostate cancer multifocality and heterogeneity, we investigated their occurrence in relation to variables such as tumour volume, local invasion, and biopsy findings. In a series of 61 completely sectioned whole-mount radical prostatectomy specimens with clinical stage T2 prostate cancer, we mapped histological grade heterogeneity and tumour multifocality. We also evaluated 55 prostate biopsy cases to assess the accuracy of pre-operative grading. Among all of the prostates, only 28 per cent had a single tumour and in 16 per cent one histological grade of cancer was evident. Extracapsular invasion was not restricted to the largest tumour in each case, but also occurred in tumours of relatively small volume and low histological grade. Variability of histological grade was directly proportional to tumour volume. Both grade heterogeneity and tumour multifocality of the prostatectomy specimen showed no significant relationship to the grade accuracy of biopsies. Biopsy grading error proved greatest among small, well-differentiated tumours. Whole-mount sectioning of prostatectomy specimens in patients with clinically localized adenocarcinoma demonstrates that grade heterogeneity is most closely related to tumour volume; that the largest (index) tumour lesion may not be representative of the pathological stage; and that grading error in prostate needle biopsies can be only partly explained by grade heterogeneity or tumour multifocality.     

Early prostate cancer detected using expression of non-functional cytolytic P2X7 receptors

AIMS: To detect early prostate cancer reliably by monitoring the expression of non-functional P2X(7) cytolytic purinergic receptors. METHODS AND RESULTS: P2X(7) receptors were absent from normal prostate epithelium obtained from post mortem tissue and tissue from cases of transurethral resection collected from young men (n = 23) who were confirmed to be free of cancer at later procedures 5-10 years after collection of the original samples. However, P2X(7) was present in every case of 116 confirmed prostate cancers regardless of Gleason grade or patient age. P2X(7) was present in apparently normal epithelial cells in acini well outside the tumour margins, but appeared in a distinct stage-specific manner commencing with the nucleus, progressing to the cytoplasm and collecting finally on the apical membrane of the epithelial cells in morphologically distinct cancer. The pattern of P2X(7) receptor localization in the epithelial cells was recorded in earlier biopsies obtained from the same patient cohort. One hundred and fourteen of 116 prostates stained positively for P2X(7) at the earliest biopsy, though generally with a less advanced pattern of distribution. CONCLUSIONS: The appearance of P2X(7) receptors in normal prostate tissue adjacent to prostate tumours makes direct tumour biopsy less critical for positive cancer diagnosis and enables cancer progression to be monitored.     

Immunohistochemical verification of ductal differentiation in prostate cancer

Recent studies have shown that patients with prostate carcinomas exhibiting ductal differentiation have an unfavourable prognosis compared with those with purely acinar adenocarcinomas. We studied the expression of nine immunohistochemical markers to evaluate their value in delineating carcinomas with and without ductal differentiation. Thirteen tumours showing cellular characteristics and growth patterns typical of ductal differentiation were identified among 110 analysed prostatectomy specimens. The levels of cytoplasmic expression of chromogranine A (69% vs 19%, p = 0.0003) and nuclear expression of p53 (76% vs 12%, p < 0.0001) as well as nuclear expression of Ki-67 (69% vs 26%, p = 0.0047) in the tumour cells, were found to be statistically significantly different in the two tumour categories. Assessment of chromogranine A, p53 and Ki-67 in prostate carcinoma may serve as useful adjunctive diagnostic tools for delineating more aggressive prostate cancer cases exhibiting ductal differentiation.     

Detection of apoptosis by the TUNEL technique in clinically localised prostatic cancer before and after combined endocrine therapy.

AIMS: Apoptosis in prostate cancer was evaluated after three months of combined endocrine therapy to investigate the association with tumour grade, tumour stage, and the immunohistochemical detection of p53 and bcl-2 in tumour cells before and after therapy. METHODS: Twenty six formalin fixed, paraffin wax embedded core biopsies and corresponding prostatectomy specimens, excised after three months of combined endocrine therapy, were analysed for the presence of apoptotic cells by the terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labelling (TUNEL) method, and for p53 and bcl-2 overexpression by immunohistochemistry. RESULTS: All 26 adenocarcinomas were clinically localised at diagnosis. In biopsies performed before combined endocrine therapy, the apoptotic indices varied between 0.09% and 1.73%, while the tumour grade fell between Gleason score 1 and 8. The mean (SD) apoptotic count pretherapy was 0.71% (0.50). There was a significant association between elevated apoptotic counts and higher Gleason scores in the biopsies (p = 0.005). After three months of therapy, the percentage of apoptotic tumour cells increased independently of tumour stage, while a significant association with Gleason grade was found (p = 0.0018) and all the tumours had Gleason scores of < 7. In eight cases the apoptotic index was more than twice its pretherapy value. The remaining tumours showed less of an increase in the apoptotic index (five cases) or a reduction in the percentage of apoptotic cells. The overall moderate increase in apoptotic index after combined endocrine therapy was not statistically significant (p = 0.8). Immunoreactivity to p53 was absent in all cases, before and after therapy, while a slight increase in the number of cells overexpressing bcl-2 was observed in five of the 13 tumours (38.1%) with reduced apoptotic indices after therapy. CONCLUSIONS: After three months of combined endocrine treatment a minority of clinically localised prostate neoplasms showed regressive epithelial alterations, associated with an increase in apoptotic tumour cells; an increase in cells overexpressing bcl-2 was observed in five of the 13 tumours with reduced apoptotic indices.     

Correlation between prostate needle biopsies and radical prostatectomy specimens can we predict pathological outcome?

Aims: Prostate needle biopsy findings provide important information when considering treatment options. We examine the correlation between needle biopsy and radical prostatectomy pathology to predict patients at high risk of harbouring adverse pathological findings. Methods: We reviewed data from 100 consecutive patients who underwent radical prostatectomy between 1 January 2003 and 31 January 2005 at the Singapore General Hospital. Pre-operative clinical findings and needle biopsy pathological data were prospectively collected and compared with the final histology. Results:The mean pre-biopsy PSA level was 9.4 +/- 5.1 microg/L. Median maximum percent of tumour in any core was 50% (range 5-100) and mean percentage of positive cores was 34.5 +/- 23%. There was under-grading of the final tumour score in 27 (27%) patients on biopsy as compared with the radical prostatectomy, while over-grading occurred in eight (8%) patients. On stratifying patients pre-operatively into low risk and high risk groups, patients in the high risk group had a significantly higher chance of having adverse radical prostatectomy histology such as extraprostatic extension, positive surgical margins or tumour volume >3.0 mL (p = 0.041, OR = 3.96, 95%CI 1.13-13.86). Conclusions: Our results demonstrated good pathological correlation between prostate needle biopsies and their radical prostatectomies. Patients with Gleason scores of 7 or more, maximum percent of tumour in any core >50%, or percent of positive cores of >50% on needle biopsy had a higher risk of having adverse pathological findings at radical prostatectomy. The converse, however, is not necessarily true, as a result of sampling error during the biopsy.     

Minimal focus of adenocarcinoma on prostate biopsy: clinicopathological correlations

AIMS: To establish the clinicopathological features of minimal volume prostate adenocarcinoma on prostate biopsy. METHODS: Twenty four cases of minimal adenocarcinoma diagnosed on prostate biopsy and treated by radical prostatectomy were reviewed. RESULTS: The major microscopic criteria were nuclear enlargement (22 of 24), infiltrative pattern (19 of 24), prominent nucleoli (19 of 24), intraluminal eosinophilic secretions (15 of 24), and high grade intraepithelial neoplasia associated (11 of 24). Sixteen of 24 cases were assigned a Gleason score 6 on biopsy. When the whole gland was assessed, 22 of these tumours were localised to the prostate (stage pT2), and only two cases were stage pT3. CONCLUSIONS: Minimal focus of adenocarcinoma on prostate biopsy is not an uncommon finding. It is usually an intermediate grade and localised stage neoplasm.     

Primary prostatic central zone adenocarcinoma

The central zone (CZ) of the prostate is embryologically, anatomically, and histologically distinct. High-grade prostatic intraepithelial neoplasia (HGPIN) and prostatic adenocarcinoma (PAC) are encountered in the CZ, but have not been well studied. Non-CZ PAC that spread into the CZ can mimic CZ PAC. We reviewed 300 consecutive radical prostatectomies performed for PAC to identify cases showing PAC and HGPIN in the CZ. There were nine PAC (3%) localized predominantly in the CZ, presenting as a single tumor nodule (8/9) and associated with 4.5+/-1.1 foci HGPIN in the CZ and with only 1.7+/-0.5 foci in the PZ. Of the 291 non-CZ PAC, 24 cases showed satellite tumor nodules in the CZ, and 92 cases demonstrated secondary contiguous spread to the CZ. As compared to the non-CZ PAC, CZ PAC tended to have lower tumor volume, but had higher Gleason scores (8.10+/-0.6 vs. 6.30+/-0.7, p<0.05), as well as a higher incidence of a ductal carcinoma component (6/9), higher rates of capsular penetration, positive resection margins (4/9), and seminal vesicle spread (2/9). The CZ HGPIN associated with CZ PAC demonstrated cells with prominent nucleoli and formed either slender papillary structures or cribriform/solid patterns. The correlating positive biopsy cores were from the mid portion or from base of prostate and contained foci of HGPIN in 4/7 cases. The CZ PAC is characteristically accompanied by more foci of HGPIN in the CZ than in non-CZ and is associated with high grade and high stage. Preoperative diagnosis of CZ PAC can be suspected due to the histopathological features in the biopsy and is important to improve the free surgical resection rate.     

Needle biopsy of recurrent adenocarcinoma of the prostate after radical prostatectomy.

The objective of this study was to evaluate needle biopsy of recurrent prostate cancer after radical prostatectomy. We evaluated 37 cases of recurrent prostate cancer after radical prostatectomy that were diagnosed by needle biopsy between March 1984 and July 1998. Fifteen were from consultations in which contributors were uncertain of the diagnosis, and 22 were from men who had come to The Johns Hopkins Hospital for treatment. The median interval from radical prostatectomy to biopsy showing recurrent tumor was 40 months. There was no correlation between the interval to recurrence and either pathologic features of the biopsy and radical prostatectomy or various clinical features. The mean extent of adenocarcinoma in the biopsies was 3.2 mm (range, 0.1 to 18 mm; median, 2 mm). The length of recurrent cancer on biopsy correlated with an abnormal rectal examination (P = .001). The mean Gleason score for the recurrent tumors was 6.5, which correlated with the grade of the radical prostatectomy cancer (P = .005). The cancers often lacked overt histologic features of malignancy. Benign prostatic acini were seen in five cases (14%), usually separate from the cancer. In 5 (33%) of the consultation cases, we would not have been able to diagnose cancer if not for the fact that atypical prostate glands should not be present after radical prostatectomy. In well-sampled radical prostatectomies, margins were almost always positive, as was extraprostatic extension. In cases with less sampling, there was a higher incidence of organ-confined disease and margin-negative disease implying suboptimal processing of the radical prostatectomy. After radical prostatectomy, recurrent cancer on needle biopsies may be focal and difficult to diagnose and must be assessed differently than in patients who have not had surgery.     

Analysis of Gleason grade and scores in 90 Nigerian Africans with prostate cancer during the period 1994 to 2004

Objectives

To determine the relative frequency of prostate cancer among surgical specimens, and among prostate specimens received at the pathology department ,University Hospital Calabar.

Methods

Histology records were reviewed for the following: total number of histology specimens received; total number of prostate specimens; total number of prostate cancer; and the total number of cancers in males during the study period. Histology sections 4–5microns thick were cut from paraffin blocks and stained by Haematoxylin and Eosin (H&E). Histopathologic specimens were classified using the grading system of tumour differentiation described by Gleason and associates.

Results

One hundred and twenty three cancers of the prostate were received, constituting 2% of the total surgical specimens and 31% of prostate specimens. Thirty three cases (27%) could not be analyzed; therefore the study is based on 90 prostate cancer specimens. Eighty nine (99%) cases were epithelial tumours (adenocarcinoma.) There was a single mesenchymal tumour (rhabdomyosarcoma) (1%). The commonest grade in this study was the high grade (Gleason grade IV).

Conclusions

We observed that prostate cancer is a common among males (all sites) diagnosed at the University Hospital Calabar, with a peak incidence between the ages of 61 – 70 years (seventh decade).     

Down-regulation of CEACAM1 in human prostate cancer: correlation with loss of cell polarity, increased proliferation rate, and Gleason grade 3 to 4 transition

Many cancers have altered expression of various cell adhesion molecules. One of these is CEACAM1, which has been found to be downregulated in several carcinomas, including prostate cancer. We explored its immunohistochemical expression in a set of 64 total prostatectomy specimens and compared it with that of the epithelial cell adhesion molecule E-cadherin and occludin, a tight junction-associated molecule. The luminal surface of the epithelial cells of normal prostate glands and ducts showed a dense expression of CEACAM1. This pattern prevailed in prostate cancer of Gleason grades 1 to 3 as long as the cells maintained their polarity and formed individual glands. With "fusion" of glands (ie, in the transition to Gleason grade 4), the expression of CEACAM1 was lost in polygonal nonpolar cells and was lost or focally very weak in cells lining a lumen in the cribriform complexes. E-cadherin, which outlined the basolateral cell membranes of contacting neighboring epithelial cells was also downregulated in prostate carcinomas. However, the loss of E-cadherin expression in higher grades was gradual and not related to the Gleason 3 to >4 transition. Occludin was also lost in polygonal (ie, unpolarized) cells of Gleason grades 4 and 5, but remained expressed in all cells facing a lumen in all grades of cancer, which CEACAM1 was not. In conclusion, downregulation of CEACAM1 as well as that of occludin in prostate cancer is associated with loss of cell polarity. It coincides with the formation of the complex glandular architecture of Gleason grade 4 pattern or complete loss thereof in Gleason grade 5 patterns. The proliferative activity, measured as Ki67 labeling index, showed a fourfold increase in the carcinoma cells with lost CEACAM1 expression, supporting previous observations that CEACAM1 regulates cell proliferation. Immunohistochemical analysis of CEACAM1 expression patterns may be useful in assessment of the malignant potential of prostate carcinoma.     

Preoperative prediction of Gleason grade in radical prostatectomy specimens: the influence of different Gleason grades from multiple positive biopsy sites.

The Gleason score of prostate adenocarcinomas is an important preoperative predictor of cancer behavior, and is used to help guide treatment. In the setting of more than two positive biopsy sites, pathologists usually grade the tumor at each site separately, and the Gleason score may differ from each positive site. This study seeks to determine if the highest Gleason score in all biopsy sites, or the Gleason score in the site with the highest tumor volume on the needle biopsy is the best predictor of final Gleason score in the radical prostatectomy specimens. Various preoperative biopsy findings were analyzed. All 151 patients had at least two positive biopsy sites and underwent radical prostatectomy. Primary and secondary Gleason pattern grades were assigned for each positive biopsy site. The tumor volume in the needle biopsy site was defined by the percentage of areas of biopsy cores involved by cancer. The radical prostatectomy specimens were completely embedded and processed in the whole-mount method. The Gleason score from both the biopsy site with the highest Gleason score and the biopsy site with the highest tumor volume on the needle biopsy correlated equally well with final Gleason score at radical prostatectomy (Spearman correlation coefficient =0.54 for both, P<0.001). The Gleason score from both the biopsy site with the highest Gleason score and the biopsy site with the highest tumor volume on the needle biopsy also correlated with primary Gleason pattern grade at radical prostatectomy (Spearman correlation coefficient =0.53 for both, P<0.001). Secondary Gleason pattern grade from the biopsy site with the highest tumor volume on the needle biopsy correlated with secondary Gleason pattern grade at radical prostatectomy slightly better than those from the biopsy site with the highest Gleason score (Spearman correlation coefficient, 0.32 vs 0.24; both P<0.001). Our data indicate that the highest Gleason score from all sites and the Gleason score from the site with the highest tumor volume on the needle biopsy are equally and significantly predictive of final Gleason score on radical prostatectomy. Both methods of prediction are significantly predictive of primary and secondary Gleason pattern grade on radical prostatectomy. We recommend that the highest Gleason score from all positive biopsy sites should be used when assigning an initial score using needle biopsies.     

Metallothionein isoform II expression in hyperplastic, dysplastic and neoplastic prostatic lesions

BACKGROUND: Metallothionein is a low-molecular-weight cysteine-rich protein that has the ability to bind and sequestrate heavy metal ions. It is associated with metalloregulatory functions such as cell proliferation, growth and differentiation. AIMS: To investigate the expression of metallothionein in hyperplastic, dysplastic and neoplastic prostatic lesions and to correlate its expression with histological grade of prostatic carcinoma. Method: The study was carried out on formalin-fixed and paraffin-wax-embedded tissue blocks from 8 patients with benign prostatic hyperplasia, 6 patients with prostatic intraepithelial neoplasia (PIN) and 30 patients with prostatic carcinoma, using the streptavidin-biotin technique. The histological grade was defined and the carcinomas were divided into low-grade (Gleason Score 2-4), 12 moderate grade (Gleason Score 5-6) and 10 high-grade (Gleason Score 7-10) carcinomas. RESULTS: Patchy metallothionein staining of epithelial cells was observed in normal and benign prostatic tissues. All cases of PIN and 20 of 30 patients with prostatic carcinoma showed positive staining for metallothionein. Metallothionein expression considerably increased from low-grade to high-grade tumours. The proportion of cells staining positively for metallothionein was directly correlated with histological grade of prostatic carcinoma. The epithelial cells lack uniformity in staining intensity, but the percentage of strongly positive cells increased with the histological grade of prostatic carcinoma. CONCLUSIONS: The high incidence of metallothionein expression in PIN in our study suggests that it is associated with early prostate tumorigenesis. Also, metallothionein expression was directly correlated with the histological grade of prostatic carcinoma, suggesting that metallothionein may be a useful marker for predicting the prognosis of prostate cancer.     

Bedeutung der Zweitmeinung bei Prostatabiopsien

Objective

The significance of a second opinion on the histological findings of prostate carcinomas as well as suspicious lesions on core needle biopsy specimens was studied in cases from the year 2008.

Study design

A total of 920 core needle biopsy specimens of the prostate were stained with H &; E and when necessary immunohistochemical analyses were performed with basal cell markers p63, 34?E12, PSA and AMACR (P504?S) and neuroendocrine markers such as synaptophysin and chromogranin. The modified Gleason grading system was used.

Results

In 43.5% of suspicious lesions adenocarcinomas of the prostate were found. In 53.2% the findings of atypical small acinar proliferations or high-grade prostatic intraepithelial neoplasia (HGPIN) were confirmed with a recommendation of serum PSA and morphological controls. The suspicion of prostatic carcinoma could be confirmed in 87.2% by the diagnosis of adenocarcinoma. After Gleason grading 82.8% of all diagnosed carcinomas had scores 6 or 7(3?+?4) and belonged to the group of low grade carcinomas. High grade carcinomas were without diagnostic problems.

Conclusion

A second opinion on the histological analysis of suspicious lesions of the prostate as well as of confirmation of Gleason grading is a very important point of quality management of diagnostic steps of prostate carcinomas and may be helpful for different therapeutic strategies.