Is there a role for prostate tumour overexpressed-1 in the diagnosis of HGPIN and of prostatic adenocarcinoma? A comparison with alpha-methylacyl CoA racemase.

Prostate Tumour Overexpressed-1 (PTOV1) was recently identified as a novel gene and protein during a differential display screening for genes overexpressed in prostate cancer (PCa). Alpha-Methyl-CoA racemase (AMACR) mRNA was identified as being overexpressed in PCa. PTOV1 and racemase were immunohistochemically evaluated in PCa, high-grade prostatic intraepithelial neoplasia (HGPIN), atrophy and normal-looking epithelium (NEp) in 20 radical prostatectomies (RPs) with pT2a Gleason score 6 prostate cancer with the aim of analyzing the differences in marker expression between PTOV1 and AMACR. The level of expression of PTOV1 and AMACR increased from NEp and atrophy through HGPIN, away from and adjacent to prostate cancer, to PCa. With the ROC curve analysis the overall accuracy in distinguishing PCa vs HGPIN away from and adjacent to cancer was higher for AMACR than for PTOV1. In conclusion, AMACR can be considered a more accurate marker than PTOV1 in the identification of HGPIN and of PCa. However, PTOV1 may aid in the diagnosis of PCa, at least to supplement AMACR as another positive marker of carcinoma and to potentially increase diagnostic accuracy.

Immunohistochemical expression and localization of somatostatin receptor subtypes in prostate cancer with neuroendocrine differentiation.

The aim of the study is to examine the tissue expression and localization of the somatostatin receptors (SSTRs) in prostate cancer (PCa) with neuroendocrine (NE) differentiation. The five SSTR subtypes (SSTR1 to 5) were evaluated immunohistochemically in the secretory cells of normal-looking epithelium (Nep), high-grade prostatic intraepithelial neoplasia (HGPIN) and PCa in 20 radical prostatectomies (RPs) with Gleason score 3+3=6 acinar PCa; 20 RPs with GS 4+4=8 and 4+5=9 PCa; and 20 RPs with PCa with NE differentiation. The basal cells were evaluated in Nep and HGPIN. In all groups the stromal smooth muscle and endothelial cells were also analyzed. Concerning the secretory cells, (i) the greatest mean proportions of cells with strong cytoplasmic staining in PCa were seen for SSTR2, mainly in the group of RP with NE differentiation, and for SSTR4 in all three groups; the mean values in HGPIN were intermediate between Nep and PCa; (ii) Membrane staining was seen for SSTR3 and SSTR4; the mean percentages of positive cells, higher in SSTR3 than in SSTR4, decreased from Nep to HGPIN and PCa in all three RP groups; in the latter two, the mean percentages were similar; and (iii) Nuclear staining was seen with SSTR4 and SSTR5; for SSTR4, the mean percentages in the PCa of the three groups were higher than in HGPIN and Nep, the highest proportion being with PCa with NE differentiation. Concerning the basal cells, in Nep the mean proportions of cells with strong staining intensity were greater for SSTR1 and SSTR3 than for the other subtypes, the lowest being with SSTR2; in HGPIN the highest mean propositions of positive cells was with SSTR3, the proportions in the three RP groups being similar. Concerning the stromal smooth muscle and endothelial cells, the highest mean values being in SSTR1 and the lowest in SSTR5; for the former subtype the highest proportion of endothelial cells with strong intensity was seen in the RP NE group. In conclusion, this immunohistochemical study expands our knowledge on the expression and localization of five SSTRs in the various tissue components in the prostate with PCa with NE differentiation, compared with conventional PCa. Typing somatostatin receptor expression in NE tumours could be of relevance to target somatostatin analogue-based diagnostic approach and treatment.

Immunohistochemical expression of prostate stem cell antigen in cystoprostatectomies with incidental prostate cancer.

High expression of prostate stem cell antigen (PSCA) has been shown to be associated with adverse prognostic features in clinically-diagnosed prostate cancer. The aim of this study is to analyze PSCA expression in cystoprostatectomies with incidental prostate carcinoma (PCa). PSCA expression was evaluated immunohistochemically in normal-looking epithelium (NEp), high-grade prostatic intraepithelial neoplasia (HGPIN) and pT2a Gleason score 6 acinar adenocarcinoma. The evaluation was carried out on 20 cystoprostatectomies (CyPs) with incidental PCa from men with bladder urothelial carcinoma (UC), and 20 radical prostatectomies (RPs) with hormonally untreated PCa from men with clinically detected PCa. Ki-67 was also investigated. The percentages of PSCA positive cells in HGPIN were significantly higher than in NEp (NEp: CyP, mean 2.92%+/-standard deviation 6.26%; RP, 3.5%+/-6.46%. HGPIN: CyP, 13.67%+/-12.78%; RP, 14.67%+/-11.34%) (p<0.001). The proportions of positive cells in PCa were greater than in HGPIN (CyP, 20.25%+/-15.96%; RP, 22.58%+/-13.67%) (p<0.001). For Ki-67 labeling, the proportions of positive nuclei in the CyPs significantly increased from NEp through HGPIN to PCa. A similar trend was seen in the RPs. In the CyPs the percentages of PSCA and Ki67 positive cells were lower than in the RPs, the differences between the CyP and RP compartments being not statistically significant. Our findings suggest that PSCA is a marker associated with neoplastic transformation of prostate cells, both in CyPs and RPs. However, there are no significant differences between CyPs with incidental prostate carcinoma and RPs with clinically diagnosed cancer.

Biology, prognosis and response to therapy of breast carcinomas according to HER2 score.

BACKGROUND: The standardization of the HER2 score and recent changes in therapeutic modalities points to the need for a reevaluation of the role of HER2 in recently diagnosed breast carcinoma. PATIENTS AND METHODS: A multicenter, retrospective study of 1794 primary breast carcinomas diagnosed in Italy in 2000/2001 and scored in HER2 four categories according to immunohistochemistry was conducted. RESULTS: Ductal histotype, vascular invasion, grade, MIB1 positivity, estrogen and progesterone receptor expression differed significantly in HER2 3+ tumors compared with the other categories. HER2 2+ tumors almost showed values intermediate between those of the negative and the 3+ subgroups. The characteristics of HER2 1+ tumors were found to be in between those of HER2 0 and 2+ tumors. With a median follow-up of 54 months, HER2 3+ status was associated with higher relapse rates in node-positive and node-negative subgroups, while HER2 2+ only in node positive. Analysis of relapses according to type of therapy provided evidence of responsiveness of HER2-positive tumors to chemotherapy, especially taxanes. CONCLUSIONS: The present prognostic significance of HER2 is correlated to receptor expression level and points to the need to consider HER2 2+ and HER2 3+ tumors as distinct diseases with different outcomes and specific features.

Immunohistochemical evaluation of global DNA methylation and histone acetylation in papillary urothelial neoplasm of low malignant potential.

A preceding study has shown that karyometry detected subvisual differences in chromatin organization status between non-recurrent and recurrent papillary urothelial neoplasm of low malignant potential (PUNLMP). The status of chromatin organization depends on epigenetic events, such as DNA methylation and histone acetylation. The aim of this study is to explore global DNA methylation and global histone acetylation in non-recurrent and recurrent PUNLMP. 5-methylcytosine (5MeC) and acetylated histone H3 lysine 9 (AcH3K9) were investigated by immunohistochemistry (IHC) in 20 PUNLMP cases (10 non-recurrent and 10 recurrent), in 5 cases of normal urothelium (NU) and in 5 cases of muscle invasive pT2 urothelial carcinoma (UC). For global DNA methylation, the mean percentage of positive nuclei in the cells adjacent to the stroma increased from NU (79%) through non-recurrent and recurrent PUNLMP (86% and 93%, respectively) to UC (97%). The percentages of positive nuclei in the intermediate cell layers and in the superficial cells in the four groups were similar to those adjacent to the stroma. The proportion of nuclei with weak-to-moderate intensity was far greater than that of those strongly stained and increased steadily from NU to UC. For global histone acetylation, the mean percentage of positive nuclei was highest in non-recurrent PUNLMP (i.e. 90%) and lowest in recurrent PUNLMP (i.e. 81%). In NU and UC the mean percentages of positive nuclei were 84% and 86%, respectively. The percentage of positive nuclei decreased from the cell layer adjacent to the stroma to the superficial cell layer. The proportion of nuclei with weak-to-moderate intensity was slightly greater than that of those strongly stained. In comparison with global DNA methylation, the proportion of strongly stained nuclei was much higher. In conclusion, there are differences in global DNA methylation and histone acetylation patterns between non-recurrent and recurrent PUNLMP. Further studies are needed to elucidate the complex interplay between chromatin structure, its modifications and recurrence of PUNLMP.

Phosphorylated mTOR is associated to androgen receptor expression in early triple-negative breast cancer.

The significance of phosphorylated mTOR (p-mTOR) expression is unknown in triple-negative breast carcinoma (TNBC). The aims of the present study were to assess the expression of p-mTOR in early TNBC and to evaluate possible correlations between androgen receptor (AR) expression, clinicopathological parameters and disease outcome. Between January 2009 and December 2013, all consecutive patients who were diagnosed and completed the treatment of invasive TNBC at our institution were eligible for this analysis. Patients with stage IV disease were excluded. The evaluation of p-mTOR immunohistochemical staining was semi-quantitatively considering both the percentage of positive tumor cells (range, 0-100%) and staining intensity (range, 0-3+). Ninety-eight TNBC patients were included. Approximately 33% of cases were p-mTOR positive and there was no association between positive immunostaining for p-mTOR and DFS (p=0.74) and OS (p=0.81). p-mTOR positivity was associated with small tumor size (p=0.03) and AR expression (p=0.04). High expression of p-mTOR may drive tumor proliferation in almost one third of TNBC. The biological association between mTOR activation and AR pathway suggests that there may exist a subgroup of TNBC in which the combination of both AR antagonism and mTOR inhibition should have a synergistic effect on cell growth and tumor progression.

Perioperative anemia and blood transfusions as prognostic factors in patients undergoing resection for non-small cell lung cancers.

We hypothesised that anemia could represent an important prognostic factor and perioperative blood transfusions do not reduce the risk of relapse. In order to explore this topic, we assessed the correlation of preoperative anemia and blood transfusions with survival in patients with resected non-small cell lung cancer (NSCLC). Patients who underwent radical surgery for NSCLC at the Department of Thoracic Surgery of Università Politecnica delle Marche from January 1996 through December 2001, were included in our study. Four hundred and thirty-nine patients were eligible for our analysis. Survival appeared worse in patients with haemoglobin (Hb) < or =10 g/dl versus Hb >10 g/dl (p=0.012). Stratifying patients in three groups on their Hb level (group 1: Hb < or =10 g/dl; group 2: Hb=10-12 g/dl; group 3: Hb > or =12 g/dl), we observed a worse prognosis in patients with lower Hb levels, too (p=0.0325) and also in the transfused population (p=0.046). At multivariate analysis, only the age of patients, pathological stage and Hb levels resulted indicators of prognosis. Our results suggested that anemia could represent an important prognostic factor in resected NSCLC and correction of anemia in the perioperative setting does not reduce the risk of relapse.

Nerve regeneration through a combined autologous conduit (vein plus acellular muscle grafts).

The authors describe nerve regeneration obtained by using a combined autologous conduit, consisting of a vein plus acellular muscle grafts. The right sciatic nerve of seven Sprague Dawley rats was transected for a length of 2 cm and the gap was filled with 2 cm long femoral vein conduit in which two autologous acellular muscle grafts had been previously inserted. Clinical and electrophysiologic tests were carried out twelve weeks after the surgical procedure. The nerve was then removed and a morphological study, including histologic examination, immunohistochemistry and quantitative analysis, was performed. The left sciatic nerve was also removed and used as a control. Regeneration was observed in the middle and distal parts of the conduit in 5 rats. Nerve conduction velocity ranged between 0 and 14.9 ms(-1). In the distal part the nerves were enclosed by a perineurium thicker than their normal counterpart and in which groups of small axons were surrounded by thin myelin sheaths. Quantitative analysis showed that the operated nerve presented a wide variation of the area of the fascicle and the density of the fibres per area, while the diameter of the axons and myelinated fibres showed only small variation, independent of the size of the fascicle. In conclusion, by using this technique, the authors succeeded in obtaining regeneration of a well formed nerve fascicle.

Nuclear changes in the normal-looking columnar epithelium adjacent to and distant from prostatic intraepithelial neoplasia and prostate cancer. Morphometric analysis in whole-mount sections.

Subtle morphological changes and molecular alterations have been reported in normal-appearing tissue in prostates with high-grade prostatic intraepithelial neoplasia (PIN) and prostate cancer (PCa). The severity and the distribution of these changes and alterations within the prostate gland have not been addressed in previous publications. The aim of this study was to investigate morphometrically the nuclear changes of the normal-looking columnar epithelium adjacent to and distant from high-grade PIN and PCa. Karyometry was performed on the whole-mount histological sections of three radical prostatectomy (RP) specimens. Two concentrical lines, one corresponding to the outer surface (or capsule) of the prostate and the other corresponding to one centimeter towards the center, were drawn with a black pen on each whole-mount section. The part of the prostate tissue between these two boundaries was then divided into twelve equal sectors or regions. The part within the inner line was divided into two regions. The analysis was also performed on the slides of the apex and base of the prostate. One prostate contained normal-looking epithelium only (case no. 1). Another contained both high-grade PIN and PCa, the former occupying larger areas than the latter (case no. 2). Both high-grade PIN and PCa were present in the third sample, in which PCa was more widely distributed than PIN (case no. 3). The lesion measured in each region was always the most severe, e.g., either high-grade PIN or PCa. When neither were identifiable, then the normal-looking columnar epithelium was analyzed. For each sector, the mean and standard deviation of the nuclear area, maximum nuclear diameter, nuclear roundness factor, and nucleolar area were calculated. In normal-looking columnar epithelium, the mean of the mean nuclear area of the sectors of case no. 1 was 35.19 microm2 (SD 4.14). The mean nuclear areas in cases no. 2 and no. 3 were 37.94 microm2 (SD 4.65) and 37.31 microm2 (SD 4.36), respectively. The mean of the mean nuclear area of the sectors with high-grade PIN of case no. 2 was 49.85 microm2 (SD 8.44), whereas it was 54.26 microm2 (SD 2.91) in case no. 3. The mean of the nuclear area values obtained in the sectors of cases no. 2 and no. 3 with PCa was 56.74 microm2 (SD 6.56) and 61.17 microm2 (SD 8.13), respectively. When considering the normal-looking tissue of the second and third case, 79% and 90%, respectively, of the regions showed nuclear area values greater than 34.94 microm2 (e.g., the 50th percentile of the mean nuclear area values of the regions of the first case). Sectors with normal-looking epithelium, whose nuclear area was above this threshold, were both adjacent to and at a distance of more than 1 cm from those with PIN or PCa. The other nuclear features showed a similar trend of value changes. This study demonstrates that the normal-looking ducts and acini from prostate harboring preneoplastic and neoplastic lesions show morphological nuclear abnormalities that are not seen by the human eyes but that can be detected with image analysis. Such changes may be of diagnostic importance, especially in cases where clinical suspicion for cancer prevails after a negative biopsy.

Centrocytic-like lymphoma associated with localized amyloidosis of the large intestine.

A case of low-grade centrocytic-like (CCL) B-cell lymphoma involving the large intestine, the regional lymph nodes and the spleen is reported. In the large intestine the lymphomatous infiltrate was restricted to sites of intense antigenic stimulation (diverticula, appendix, ileo-caecal valve) and was associated with marked plasma cell differentiation and massive amyloid deposits. The immunophenotype was CD20, CD21, CD45RA/MB1/MT2, CD68, CD45 related/Ki-B3 and HLA-DR positive, and MB2, DBA.44 reactive regarding the CCL cell lymphoma subpopulation; and IgG-lambda positive regarding its plasma cell fraction.

Morphometric index of adult renal cell carcinoma. Comparison with the Fuhrman grading system.

Various grading systems have been proposed for renal cell carcinoma (RCC), using nuclear, cytoplasmic, and architectural features. The available evidence suggests that nuclear grading is a better prognostic indicator than other types of grading schemes. Nuclear morphometry may still improve the correlation of the nuclear grading with survival, however, because observer consistency is lacking in the subjective grading of RCC. The aim of this study was to investigate morphometrically whether RCC cases show a continuous spectrum of nuclear changes or whether there are discrete groups of cancer that correspond to the four Fuhrman grades. Karyometry was performed on 5- microm-thick, haematoxylin- and eosin-stained sections from 60 cases of conventional (clear cell) RCC. The analysis also included the evaluation of normal renal tissue (proximal tubules) adjacent to cancer. In each case the difference between the value of the cancer and the corresponding normal epithelium was calculated to represent, quantitatively, the degree of similarity between the tumour tissue and the internal normal control. When the differences were sorted into ascending order, a steady increase in values was observed for both the nuclear and the nucleolar features. A monotonic trend was evident for the differences in the mean maximum nuclear diameter and mean nucleolar area. When the differences between the values in the cancer and in the corresponding normal epithelium of these two features were summed up, the method resulted in a continuous variable, or nuclear morphometric index, related to the degree of deviation of each individual RCC from its internal normal control. The lowest index values were observed in of Fuhrman grade I cases, whereas values ranging from 2.679 to 5.422 were associated with cases graded II. Values equal to or higher than 5.951 were seen in the cases assigned to either grade III or grade IV. Partial overlap was present between the index values in grades III and IV. The RCC cases can be represented by a continuous index that corresponds to the morphological grading based on the Fuhrman scheme. This study shows that the index may be useful in supplementing the pathologist's grading. This issue can be further addressed with follow-up studies.

Computed cell cycle and DNA histogram analyses in image cytometry in breast cancer.

AIMS: To analyse the cell cycle and DNA histogram components in data from DNA static cytometry and, in particular, to investigate the influence of the length of time the slides are exposed to the light of the cytophotometer in evaluating the G0/G1 peak. METHODS: DNA static cytometry was performed on 18 Feulgen stained imprints and six histological sections taken from six breast carcinomas. The total optical density values obtained were analysed using software commercially available as Multicycle. DNA flow cytometry was performed on the same cases. RESULTS: The proportions of nuclei related to the cell cycle components from DNA static cytometric data, obtained from Feulgen stained cytological smears, were almost identical with those obtained from DNA flow cytometric data. Moreover, additional information was obtained from the DNA static cytometry frequency histogram and the proportions of nuclei below the diploid G0/G1 peak and above the G2 phase. Discrepancies between DNA static cytometry and DNA flow cytometry were seen in the large coefficients of variation of the G0/G1 peaks obtained with the former method of analysis, even though a better correspondence was found when the exposure time of the slides to the light of the cytophometer was conspicuously shortened. The information obtained from histological sections seemed to be similar to that obtained from DNA flow cytometry when a single cell population was present; a single cell population was detected in two out of the three cases in which two distinct populations had been present in DNA flow cytometry. CONCLUSIONS: The computer analysis of DNA static cytometric data obtained from Feulgen stained cytological specimens provides the type of information on the cell cycle which is usually obtainable only from DNA flow cytometry. Correspondence with the DNA data from histological sections, however, was poor.

Effects of complete androgen blockade for 12 and 24 weeks on the pathological stage and resection margin status of prostate cancer.

AIMS: To compare the pathological stage and surgical margin status in patients undergoing either immediate radical prostatectomy or 12 and 24 weeks of neoadjuvant hormonal treatment (NHT) in a prospective, randomised study. METHODS: Whole mount sections of 393 radical prostatectomy specimens were evaluated: 128 patients had immediate surgery, 143 were treated for 12 weeks and 122 for 24 weeks with complete androgen blockade. RESULTS: Histopathology revealed organ confined tumours in 40.4% of patients with clinical stage B disease in the immediate surgery group, whereas 12 and 24 weeks of NHT increased the number of organ confined tumours to 54.6% and 64.8%, respectively. Among patients with clinical stage C tumours, pathological staging found organ confined disease in 10.4%, 31.4%, and 61.2% in the immediate surgery, 12 weeks of NHT, and 24 weeks of NHT groups, respectively. Preoperative NHT caused a significant decrease in positive margins both in patients with clinical stage B and C disease. The extent of margin involvement was not influenced by preoperative treatment. CONCLUSIONS: Neoadjuvant androgenic suppression is effective in reducing both the pathological stage and the positive margin rate in patients with stage B and C prostatic cancer undergoing radical surgery. Some beneficial effects are evident in those patients treated for 24 weeks, and it is reasonable to assume that the optimal duration of NHT is longer than three months.

Expression of proliferating cell nuclear antigen in ameloblastomas and odontogenic cysts.

The identification of the proliferative activity in tumours may be useful to predict the biological behaviour of different lesions. Proliferating cell nuclear antigen (PCNA) has been used for the evaluation of the proliferative ability of many lesions. In this study 22 ameloblastomas (4 follicular, 5 plexiform, 4 acanthomatous, 5 unicystic, 4 recurrent), 12 odontogenic keratocysts (OKC), 8 dentigerous cysts (DC), and 12 radicular cysts (RC) were analysed. PCNA+ cells were present in all cyst types but the OKC contained the highest number of PCNA+ cells. In OKC the location of PCNA+ cells was mainly suprabasal. In ameloblastoma PCNA+ cells were located mainly in the peripheral portion of the tumour islands. Statistical analysis showed that ameloblastoma had higher PCNA+ cell counts than OKC (P < 0.0001); OKC had higher values than DC and RC (P < 0.0001). Recurrent ameloblastoma presented higher PCNA+ cell counts than other types of ameloblastoma, while unicystic ameloblastoma showed lower values than acanthomatous, plexiform and follicular ameloblastomas (in this latter case the difference was not statistically significant). These data could help to explain the different biological behaviour of these lesions.

bcl-2 expression and apoptotic bodies in 13-cis-retinoic acid (isotretinoin)-topically treated oral leukoplakia: a pilot study.

In a double-blind study 10 patients with oral leukoplakia were treated daily (three topical applications) with 0.1% isotretinoin gel or a placebo for 4 months. Nine patients completed the treatment, while one patient was lost to follow-up. Subsequently, the patients who had received the placebo used the active medication for an additional 4 months. All patients treated with the active medication showed a significant improvement of the oral lesions while, in the patients receiving only the placebo, the size of the lesions remained the same. Also the group of patients who received the active medication after the placebo showed an improvement in the size and clinical appearance of the lesions. A complete response was defined as the complete disappearance of the lesion as assessed by visual inspection, while a partial response was defined as a 50% or more reduction in the size of the lesions. In total we had a complete response and eight partial responses. No side-effects from the use of the gel were ever observed. The percentage of bcl-2-positive cells was evaluated in the basal layer from a minimum of 1000 cells in each case and the bcl-2 immunostaining was scored using three groups: - (< or = 10% cells); + (< or = 50% cells); +2 (> or = 50% cells). The presence of apoptotic bodies was evaluated in a random fashion in the parabasal layer in 20 HPF. Immunohistochemical analysis for bcl-2 protein showed that before treatment a weak positivity of the basal layers, with a focal positivity of some parabasal cells, was present: five out of nine specimens were positive. Only a few apoptotic bodies were observed. After treatment in almost all specimens it was possible to observe a complete bcl-2 negativity with a positivity in only one specimen out of nine. An increase in apoptotic bodies was observed. Statistical analysis showed that the difference between the bcl-2 positivity in the two groups was not statistically significant (P = 0.134) while, on the contrary, the difference in the count of the apoptotic bodies between the same two groups was statistically significant (P = 0.0193). In conclusion, the data obtained from this pilot study show that good results can be obtained with the topical use of 13-cis-retinoic acid.

Microvessel density (MVD) and vascular endothelial growth factor expression (VEGF) in human oral squamous cell carcinoma.

BACKGROUND: Carcinogenesis is thought to be dependent on neovascularization. Vascular endothelial growth factor (VEGF) is a glycoprotein that has the capability of increasing vascular proliferation and permeability. VEGF has been found to be expressed in several different types of tumours and it may contribute to the progression of malignant tumours. Increased microvessel density (MVD) has been described in oral squamous cell carcinoma (OSCC) and seems to be related to patient prognosis. MATERIALS AND METHODS: Fifty-two cases of OSCC were evaluated in the present study. Immunostaining for VEGF and Factor-VIII was performed. The MVD was evaluated in G1, G2 and G3 tumours. RESULTS: The differences between these 3 groups were statistically significant (p = 0.0331). MVD was also evaluated in lymph-node negative and lymph-node positive cases: the differences between these two groups were statistically significant (p < 0.0001). VEGF expression was evaluated in G1, G2 and G3 tumours. The differences between the 3 groups were not statistically significant (p = 0.289), even if an increasing trend in the VEGF positivity was evident from G1 to G3. The difference of VEGF expression between tumours with and without lymph node metastases was not significant (p = 0.196). No correlation was present between intensity of VEGF positivity and histological grading or lymph-node status and between VEGF and MVD. CONCLUSION: Our data showed that MVD was correlated with grading and lymph-node status, while no similar correlation was found for VEGF.

Urothelial papillary lesions. Development of a Bayesian Belief Network for diagnosis and grading.

The diagnosis and grading of urothelial papillary lesions are affected by uncertainties which arise from the fact that the knowledge of histopathology is expressed in descriptive linguistic terms, words and concepts. A Bayesian Belief Network (BBN) was used to reduce the problem of uncertainty in diagnostic clue assessment, while still considering the dependencies between elements in the reasoning sequence. A shallow network was designed and developed with an open-tree topology, consisting of a root node containing four diagnostic alternatives (papilloma, papillary carcinoma grade 1, papillary carcinoma grade 2 and papillary carcinoma grade 3) and eight first-level descendant nodes for the diagnostic features. Six of these nodes were based on cell features and two on the architecture. The results obtained with prototypes of relative likelihood ratios showed that belief in the diagnostic alternatives is very high and that the network can identify papilloma and papillary carcinoma, including their grade, with certainty. In conclusion, a BBN applied to the diagnosis and grading of urothelial papillary lesions is a descriptive classifier which is readily implemented and allows the use of linguistic, fuzzy variables and the accumulation of evidence presented by diagnostic clues.

Surgical pathology examination of radical prostatectomy specimens. Updated protocol based on the Italian TAP study.

Between January 1996 and June 2000, 192 men with prostate cancer underwent radical retropubic prostatectomy (RP) and bilateral pelvic node dissection in 26 centers participating in the Italian randomized prospective TAP study. The reviewing pathologist evaluated 145 RP specimens. Seventy-five cases had not been treated with total androgen ablation before RP was performed, whereas 70 had been treated for three months. Whole-mount sectioning of the complete radical prostatectomy specimens was adopted in each center for accurately evaluating the pathological stage of prostate cancer and resection limit status. The results of this study suggest that total androgen ablation before RP is beneficial in men with clinical stage T2 because of the significant pathological down-staging and decrease in the number of positive margins in the RP specimens. On the basis of the experience acquired through the Italian TAP study and recent publications on prognostic factors in prostate cancer, the original practice protocol for examination of RP specimens removed from patients with carcinoma of the prostate glands was updated.

Prostatic intraepithelial neoplasia and prostate cancer.

Prostatic intraepithelial neoplasia (PIN) is composed of dysplastic cells with a luminal cell phenotype, expressing the androgen receptor as well as prostate specific antigen. PIN is characterized by progressive abnormalities of phenotype which are intermediate between normal prostatic epithelium (NP) and cancer, indicating impairment of cell differentiation and regulatory control with advancing stages of carcinogenesis. High-grade PIN is considered the most likely precursor of prostatic carcinoma (PCa), according to virtually all available evidence. Androgen deprivation decreases the prevalence and extent of PIN and the degree of capillary vascularization (e.g., angiogenesis) in the surrounding stroma via the suppression of vascular endothelial growth factor (VEGF) production. It is likely that PCa might also arise from precursor lesions other than high-grade PIN (low-grade PIN, atypical adenomatous hyperplasia, malignancy-associated foci, and atrophy).