Biomedical subjects

R Pomante

Publications and source records attributed to R Pomante.

15 recordsLinked to original sources

PubMed2000

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.

Adult↗

PubMed2000

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.

Aged↗

PubMed2000

Expression of pi-class glutathione S-transferase: two populations of high grade prostatic intraepithelial neoplasia with different relations to carcinoma.

BACKGROUND/AIMS: Patients with high grade prostatic intraepithelial neoplasia of the transition zone appear to be at increased risk of developing prostatic carcinoma, although not to the same degree as patients with high grade prostatic intraepithelial neoplasia of the peripheral/central zone. Previous investigations have shown loss of expression of pi-class glutathione S-transferase (GST-pi; an enzyme that protects against electrophilic carcinogens) in prostatic carcinoma and in high grade prostatic intraepithelial neoplasia. The aim of this study was to compare the expression of GST-pi in high grade prostatic intraepithelial neoplasia of the transition zone with that in high grade prostatic intraepithelial neoplasia of the peripheral/central zone (that is, non-transition zone). METHODS: Immunostaining with the anti-GST-pi antibody was performed on 20 high grade prostatic intraepithelial neoplasia samples of the transition zone, either isolated or associated with prostatic carcinoma (groups 1 and 2, respectively; 10 cases each) and on 20 high grade prostatic intraepithelial neoplasia samples of the non-transition zone, either isolated or associated with prostatic carcinoma (groups 3 and 4, respectively; 10 cases each). This study also included six samples of high grade prostatic intraepithelial neoplasia simultaneously present in the transition and non-transition zones and not associated with prostatic carcinoma (group 5). The presence of immunostaining, staining intensity, and the distribution of immunostaining were evaluated in the high grade prostatic intraepithelial neoplasia lesions and in the normal tissue and cancer areas. RESULTS: The GST-pi antibody stained the cytoplasm of the cells lining the ducts and acini of normal prostate tissue. Staining was stronger and more diffuse in the basal cell layer than in the luminal (or secretory) cell layer. Immunohistochemical staining with anti-GST-pi antibodies failed to detect the enzyme in all prostatic carcinoma foci but one. Two patterns were detected in high grade prostatic intraepithelial neoplasia. One was represented by GST-pi staining similar to that of the normal tissue (pattern A). The other deviated from it and was characterised by absence of GST-pi expression in the secretory cells and abundant expression in scattered basal cells (pattern B). Pattern A staining was seen more frequently in the transition than in the non-transition zone. Pattern B staining was seen mainly in high grade prostatic intraepithelial neoplasia of non-transition zone associated with cancer. CONCLUSIONS: The differential expression of GST-pi in the transition and non-transition zones indicates the existence of two populations with the morphological appearance of high grade prostatic intraepithelial neoplasia that might have different associations with carcinoma.

Aged↗

PubMed2000

Prostate tissue and serum markers.

Serum prostate specific antigen (PSA) is elevated beyond the arbitrary cut-off point of 4.0 ng/ml in the majority of patients with prostate cancer (PCa). It may also be greater than 4.0 ng/ml in some benign conditions, including benign prostatic hyperplasia (BPH). Therefore, serum PSA lacks high sensitivity and specificity for PCa. This problem has been partially overcome by calculating several PSA-related indices (such as PSA density, PSA velocity, percent free PSA) and/or evaluating other serum markers (such as human glandular kallikreins and prostate specific membrane antigen). Atypical small acinar proliferation (ASAP) often represents the underdiagnosis of cancer in biopsy material; patients with cancer on the repeat biopsy usually have an elevated serum PSA. Whether the determination of serum PSA can be of help in the identification of patients with isolated prostatic intraepithelial neoplasia (PIN), i.e., long before PCa develops, is still being debated

Humans↗

PubMed1999

Inference network-based analyses of the histopathological effects of androgen deprivation on prostate cancer.

The evaluation of prostate cancer histology following hormonal therapy often represents a diagnostic problem for the pathologist. Previous studies have shown that an inference or Bayesian belief network (BBN) offers a descriptive classifier useful for the accurate analysis of morphological changes in individual cases of prostate neoplasia. Three different BBNs were evaluated in 94 cancer foci present in 20 radical prostatectomy (RP) specimens and in the matching biopsies in which the initial diagnosis of prostatic adenocarcinoma was made. Ten RP specimens were from patients treated with total androgen ablation or combination endocrine therapy (CET) before surgery. The first and second BBN allowed the identification with high certainty of the cancer foci present in the biopsies and RP specimens, as well as their Gleason grade, the belief value often being close to 1.0. The results of the second BBN showed a good correspondence between the Gleason grade given in the biopsies and that in the RP specimens, except in the surgical material of the treated patients, in which upgrading was always present. The third BBN showed the existence of three subgroups in treated RP specimens, one with morphological effect, another with poor effect, and the third with the histology of untreated (i.e. unaffected) cancer. In conclusion, an inference network-based analysis allows the characterization of treated prostate cancers according to the degree of histopathological change.

Adenocarcinoma↗

PubMed1999

Immunohistochemical expression of pi class glutathione S-transferase in the basal cell layer of benign prostate tissue following chronic treatment with finasteride.

BACKGROUND: Glutathione S-transferases (GST) may prevent carcinogenesis through inactivation of reactive electrophiles by conjugation to reduced glutathione. Treatment directed at the induction or preservation of GST-pi expression in normal epithelium could have a profound impact on the prevention of prostate neoplasia. Finasteride, a 5-alpha-reductase inhibitor, is used as a chemopreventive agent because it blocks the conversion of testosterone to its byproduct which promotes prostate tumour growth. OBJECTIVE: To investigate GST-pi expression immunohistochemically in benign prostate tissue from untreated patients and from patients chronically treated with finasteride. MATERIALS: Immunostaining with anti-GST-pi antibody was performed on 10 (cysto-) prostatectomy, eight simple prostatectomy, and three transurethral prostatectomy specimens. The first set of 10 prostates was from untreated patients operated on for bladder cancer. The other cases were from patients with benign prostatic hyperplasia and chronically treated with finasteride. None of the specimens in either group showed prostatic cancer, prostatic intraepithelial neoplasia, urothelial carcinoma, or chronic prostatitis. Specimens were evaluated for the presence, intensity, and distribution of immunostaining. RESULTS: Diffuse cytoplasmic immunostaining was observed in the basal cell layer of the untreated specimens. Some variability in the expression of GST-pi was seen within each zone and also between the prostate zones. Only a minority of the secretory cells was stained weakly, mainly in the subnuclear region of the cells facing an uninterrupted basal cell layer. Staining was more homogeneously diffuse in the cytoplasm of the luminal cells facing the basement membrane directly. In the benign epithelium of the finasteride treated specimens the circumferential staining of the basal cells appeared to be more continuous than in the untreated cases, the gaps in the stained basal cell layer being fewer, shorter, or even absent in some ducts and acini. There was no variability in the intensity of staining of the basal cell layer, all the cells being intensely stained in a uniform way. The intensity of staining of the secretory cells was not influenced by finasteride treatment. CONCLUSIONS: Following chronic treatment with finasteride the immunohistochemical expression of pi class glutathione S-transferase in the benign prostate ducts and acini is upregulated in relation to an expanded basal cell layer. This could indicate that finasteride acts as a GST-pi inducer.

Aged↗

PubMed1999

Nodular hyperplasia of the prostate. Quantitative evaluation of secretory cell changes after treatment with finasteride.

OBJECTIVE: To quantitatively evaluate the changes in the secretory cells in nodular hyperplasia of the prostate after treatment with finasteride. STUDY DESIGN: Secretory cell nuclear and nucleolar measurements were performed with an image analyzer in hematoxylin-and-eosin-stained sections of 20 untreated and 20 finasteride-treated cases of nodular hyperplasia. An immunoperoxidase method was used to stain the secretory cells with a monoclonal antibody-directed, anti-prostate specific antigen (PSA). The size of prostates was determined by transrectal ultrasound. For both groups the serum PSA values were determined. RESULTS: After six months of treatment with finasteride, the prostates shrank by approximately 20% with the therapeutic regimen (as determined by transrectal ultrasound), whereas the serum PSA values decreased by 30% (before therapy, < 4.00 ng/mL). The secretory cells appeared smaller than those from the untreated group of patients, and the cytoplasm staining of the PSA marker was slightly diminished. Karyometric analyses showed that the nuclear and nucleolar size were smaller in comparison with the controls. In particular, the mean nuclear and nucleolar area in the treated group were, respectively, 34.12 and 1.424 micron 2, whereas in the untreated group the values were 40.46 and 2.261. CONCLUSION: Reduced androgen stimulation after treatment with finasteride induces involution of secretory cells. This may be responsible for the decrease in the serum PSA level and may contribute to the reduction in prostate size.

Aged↗

PubMed1999

Changes in the normal-looking epithelium in prostates with PIN or cancer.

BACKGROUND: In prostatic neoplasia, the time from tumour initiation and progression to invasive carcinoma often begins in men in the fourth and fifth decades of life and extends across decades. Until recently, the events initiating the process and the developments concomitant with the evolution towards invasive disease were largely unknown. METHODS: Quantitative and analytical methods are applied to provide insights into certain individual molecular events and their effects on the complex multiple feedback system of cellular metabolism and regulation in prostate neoplasia. RESULTS: Prostatic intraepithelial neoplasia (PIN) and prostate cancer (PCa) are associated with or possibly preceded by changes in the chromatin of secretory cell nuclei. The changes are detectable with a Bayesian belief network and quantifiable by computer image analysis in prostatic tissue that still appears histologically normal. In addition, normal looking prostate epithelium shows some molecular changes similar to those present in the associated preneoplastic and neoplastic lesions. Such changes are also occasionally present in normal prostate glands without PIN and cancer. CONCLUSIONS: The subtle morphological and molecular changes of normal looking epithelium might be seen as the onset of the development of prostatic neoplasia.

Adenocarcinoma↗

PubMed1998

Apoptosis in prostatic adenocarcinoma following complete androgen ablation.

OBJECTIVE: To analyze the cell death phenomenon in prostate cancer following complete androgen ablation. METHODS: The frequency and location of apoptotic bodies (ABs) were evaluated in haematoxylin and eosin stained sections of radical prostatectomy specimens from patients with invasive prostatic adenocarcinoma treated with neo-adjuvant endocrine combination therapy for 3 months before surgery. The results were compared with an untreated age- and stage-matched control group. RESULTS: Both in treated and untreated prostate tissue the AB frequency increased from normal prostate, through prostatic intraepithelial neoplasia, up to prostatic adenocarcinoma. The main location was in the cell layers adjacent to the stroma, their frequency decreasing towards the lumen. The frequency of ABs was higher in the treated prostate glands than in the untreated groups. The relative increase of the AB frequency in treated carcinomas as compared with untreated ones was lowest in tumours with a solid pattern, intermediate in the cribriform, and highest in the acinar pattern. CONCLUSIONS: Complete androgen ablation induces involution of prostate tissue mainly through the enhancement of apoptosis. This type of cell death is thought to play a major role and might be linked to specific changes in signal transduction mechanisms in response to hormonal withdrawal.

Adenocarcinoma↗

PubMed1998

Prostatic intraepithelial neoplasia and prostate cancer: analytical evaluation.

For urologists and pathologists one of the two main issues in prostate pathology is the identification of those prognostic factors that could predict the exact outcome of individual patients with prostate cancer (PC). Therefore, the goal is to tailor the therapeutic approach to the clinical, morphological and biological features of each patient. The other issue involves the early detection of PC, preferably in the preinvasive phase, in order to treat the patient efficaciously. For this reason, understanding the biology of preinvasive or precursors lesions has become increasingly important. Prostatic intraepithelial neoplasia is only one of these lesions, and the best known to date. The role of others, such as atypical adenomatous hyperplasia, is considered as worth exploring. Prostatic intraepithelial neoplasia (PIN) represents the putative precancerous end of the morphologic continuum of cellular proliferations within prostatic ducts and acini. Two grades of PIN are identified (low grade and high grade), and high grade PIN is considered the direct precursor of invasive carcinoma. The continuum which culminates in high grade PIN and early invasive cancer is characterised by basal cell layer disruption, basement membrane disruption, progressive loss of markers of secretory differentiation, increasing nuclear and nucleolar abnormalities, increasing proliferative potential, and increasing variation in DNA content (aneuploidy). Clinical studies suggest that PIN predates carcinoma by ten years or more, with low grade PIN first emerging in men in the third decade of life. The clinical importance of recognising PIN is based on its strong association with carcinoma; its identification in biopsy specimens of the prostate warrants further search for concurrent invasive carcinoma. The issue of precursors of prostate cancer has several facets which reflect the multiplicity of patterns and variants of PC. A big step forward in understanding some basic aspects has already been made, especially in relation to PIN. More will be available soon. A large contribution to the management of isolated PiN lesions found in prostate biopsies is expected from molecular pathology and quantitation analysis.

Journal Article↗

PubMed1997

Subtle changes in benign tissue adjacent to prostate neoplasia detected with a Bayesian belief network.

The aim of this paper was to test the usefulness of a Bayesian belief network (BBN) as a decision support system in the uncertainty assessment of benign prostatic tissue, either associated or not with inflammation or adjacent to prostatic adenocarcinoma (PAC) or prostatic intraepithelial neoplasia (PIN). A shallow network was used with eight first-level descendant nodes for the diagnostic clues, each independently linked by a conditional probability matrix to a root node containing the diagnostic alternatives. One diagnostic evidence node was based on the tissue architecture and the others were based on cell features. The efficacy of the network was tested on a series of 45 simple prostatectomy specimens, subdivided as follows; benign prostatic tissue not associated with other diseases (15 cases), associated with acute and/or chronic inflammation (15 cases), and adjacent to accidentally discovered PAC or PIN (15 cases). The highest belief values for the diagnostic alternative normal prostate (NP) were obtained in the 15 cases not associated with other diseases, the mean value being 0.996. The 15 cases evaluated in areas with inflammation showed the lowest belief values for NP (mean 0.774). For the 15 cases evaluated in specimens with PAC or PIN, the belief values for NP were intermediate between those from normal prostatic tissue associated with inflammation and those not associated (mean 0.925). Moreover, it was found that subtle changes were also present at a certain distance from the tumour. In conclusion, the network can be used as a decision support system to differentiate with high certainty benign prostate adjacent to PAC or PIN from benign prostatic tissue either associated or not with inflammation. The subtle morphological alteration detected with the BBN may be considered malignancy-associated changes.

Adenocarcinoma↗

PubMed1997

Diagnostic distance of high grade prostatic intraepithelial neoplasia from normal prostate and adenocarcinoma.

OBJECTIVE: To develop a distance measure based methodology to support the morphological evaluation of high grade prostatic intraepithelial neoplasia (PIN), a direct precursor of prostate cancer. METHODS: Eight morphological and cellular features were analysed in 20 cases of high grade PIN found in radical prostatectomy specimens from patients with adenocarcinoma. The diagnostic distance was evaluated to measure the extent to which the feature outcomes of the individual high grade PIN cases differed from the expected outcome profile of normal prostate, low and high grade PIN, and cribriform and large acinar adenocarcinoma. The belief value for high grade PIN was evaluated with a Bayesian belief network (BBN). RESULTS: Complete separation existed between the cumulative absolute diagnostic distances of these 20 cases from the prototype feature outcomes of high grade PIN and normal prostate the values for which were < or = 3 (range 0 to 3) and > or = 9 (range 9 to 15), respectively. The distances from low grade PIN (range 3 to 9), cribriform adenocarcinoma (range 2 to 8), and large acinar adenocarcinoma (range 5 to 10) were intermediate and showed overlap in their distribution. When taking into consideration whether the severity of feature changes was increasing or decreasing in comparison with the category prototype outcomes, the cumulative directional diagnostic distances from high grade PIN ranged from -3 to +3. Positive distance values were seen relative to low grade PIN (range +3 to +9) and relative to normal prostate (range +9 to +15). Negative values were found relative to cribriform adenocarcinoma (range -8 to +2). The distance values from large acinar adenocarcinoma ranged from -2 to +4 and partly overlapped with those from the high grade PIN category. A bivariate scattergram derived from both diagnostic distance measures showed excellent separation between the groups' distances. BBN analysis confirmed the morphology based diagnosis. The distance evaluation resulted in 18 cases whose belief value for high grade PIN ranged from 0.60 to 0.87. In the remaining two cases the results of the BBN analysis showed a belief value of 0.50 and 0.57 for low grade PIN and of 0.49 and 0.38 for high grade PIN, respectively. CONCLUSIONS: Distance measure based methodology represents a useful diagnostic decision support tool for the accurate evaluation of high grade PIN.

Adenocarcinoma↗

PubMed1997

Preneoplastic lesions of the prostate.

Journal Article↗

PubMed1996

Evaluation of prostatic intraepithelial neoplasia after treatment with a 5-alpha-reductase inhibitor (finasteride). A methodologic approach.

OBJECTIVE: To develop a methodology applicable to the morphologic study of the efficacy of finasteride on prostatic intraepithelial neoplasia (PIN), a putative precursor of prostate cancer. STUDY DESIGN: Three PIN foci were reviewed in two simple prostatectomy specimens from patients with clinical diagnoses of benign prostatic hyperplasia and treated with finasteride for six months. The feasibility of PIN diagnosis and grading based on "diagnostic distance" was investigated. It is a measure of the "extent" to which the observed features are different from those of the untreated prototypes representing the following diagnostic categories: normal prostate, low and high grade PIN and prostatic adenocarcinoma with a cribriform or large acinar pattern. Uncertainty in the PIN diagnosis and grading was dealt with by means of a Bayesian belief network (BBN). RESULTS: The distance measure values of the three PIN foci from the prototype of untreated, nonneoplastic prostate were 9, 7 and 8, respectively, in relative, arbitrary units. Their distance from the two prostate cancer patterns (large acinar and cribriform) was as high as 8-10. The distance of these foci from either low or high grade PIN were as low as 5, 3 and 2, and 3, 5 and 4, respectively. BBN produced the highest belief values for PIN, thus confirming the morphology-based and diagnostic distance-supported diagnosis; however, the belief values were low for both grades. CONCLUSION: The results provided by BBN analyses and diagnostic distance measures support the conclusion that this methodology is applicable to assessing the efficacy of finasteride treatment of PIN.

5-alpha Reductase Inhibitors↗

PubMed1977

Verrucous carcinoma arising from an artificial vagina.

Verrucous carcinoma is a well known and extensively reported entity in the English literature. It can occur in many tissues including vaginal mucosa. The first report of this entity occuring in an artificial vagina, including typical gross and histologic features, is presented with a discussion of the literature. The best mode of therapy remains primary excision of the lesion, and prognosis is excellent if early surgical intervention is accomplished.

Carcinoma, Papillary↗