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Rodolfo Montironi

Publications and source records attributed to Rodolfo Montironi.

At least 19 recordsLinked to original sources
PubMed2006

Amplifications of EGFR gene and protein expression of EGFR, Her-2/neu, c-kit, and androgen receptor in phyllodes tumor of the prostate.

Phyllodes tumor of the prostate is a rare neoplasm with an unpredictable clinical behavior. It may undergo early recurrence with sarcomatous transformation or may even metastasize. Because targeted therapies have shown great success against several malignancies, there is hope that these same therapies may show similar promise in the treatment of other neoplasms. This study was undertaken to investigate both amplification of the epidermal growth factor receptor (EGFR) gene by fluorescence in situ hybridization and the overexpression of EGFR, Her-2/neu, CD117 (c-kit), and androgen receptor by immunohistochemical staining in a series of 11 phyllodes tumors of the prostate. In the stromal elements, EGFR gene amplification was present in four of 11 tumors and polysomy chromosome 7 was present in two of 11 tumors. No amplification was present in the epithelial components. Only one of 11 tumors had polysomy of chromosome 7 in the epithelial components. Immunohistochemically, in the stromal components, EGFR expression was demonstrable in four of 11 tumors and androgen receptor was demonstrated in six of 10 tumors. Neither Her-2/neu nor c-kit expression was seen in the stromal components of any of the 11 tumors. In the epithelial components, EGFR expression was present in all 11 tumors with strong staining in the basal cell layers and weak or no staining in luminal epithelium; androgen receptor expression was seen in seven of 10 tumors; Her-2/neu was weakly positive in four of 11 tumors; and c-kit expression was present focally and weakly in two of 11 cases with only 2-5% of cells staining. The highest staining intensity and the highest percentage of positively staining cells were seen with EGFR immunostaining in both the stromal and epithelial (mainly basal cells) components. Androgen receptor staining showed the next highest staining intensity and percentage of positive cells in both components. Her-2/neu and c-kit were only weakly or infrequently expressed in the epithelial components of prostatic phyllodes tumors. Our data indicate that EGFR and androgen receptor are frequently and strongly expressed in both epithelial and stromal components of prostatic phyllodes tumors. EGFR gene amplification is frequently present in prostatic phyllodes tumors and may account for one of the mechanisms leading to protein overexpression in some but not all cases. Anti-EGFR and/or antiandrogen agents may be potentially useful for management of patients with tumors expressing EGFR and/or androgen receptor.

Adult↗
PubMed2006

Natural history of urothelial inverted papilloma.

BACKGROUND: Inverted urothelial papilloma is an uncommon urothelial neoplasm. Although it is traditionally regarded as a benign tumor, conflicting data on multiplicity, recurrence rate, and association with urothelial carcinoma have left uncertainties concerning its biologic behavior. METHODS: The authors analyzed the clinicopathological characteristics of 75 cases of inverted papilloma in the urinary tract without prior or concurrent urothelial carcinoma to determine its biologic behavior and prognosis, and to correlate these findings with surveillance strategies. RESULTS: These patients ranged in age from 26 to 85 years (mean, 60 years). Of the 46 patients for whom tobacco use history was available, 28 gave a history of smoking. Inverted papillomas were located in the urinary bladder (67 cases), prostatic urethra (4 cases), and ureter (4 cases). The majority of vesical tumors arose from the trigone or near the bladder neck. Common presenting complaints included hematuria, dysuria, and irritative voiding symptoms. In 1 case of vesical inverted papilloma, there was a recurrence. All other patients were free of tumor recurrence or progression during a mean follow-up of 68 months (range, 2-240 months). CONCLUSIONS: Both the extremely low incidence of tumor recurrence (1%) and strikingly favorable prognosis suggest that inverted urothelial papilloma, when diagnosed according to strictly defined criteria, is a benign urothelial neoplasm not related to urothelial carcinoma. Therefore, complete transurethral resection of inverted papilloma is adequate surgical therapy, and surveillance protocols as rigorous as those employed in the management of urothelial carcinoma seem unnecessary.

Adult↗
PubMed2006

BCL-2, TP53 and BAX protein expression in superficial urothelial bladder carcinoma.

Whether TP53, BCL-2 and BAX expressions add independent prognostic information in patients with Ta/T1 bladder urothelial carcinoma remains unclear. TP53 overexpression correlated with high tumor grade (p=0.004), WHO grading categories (0.045), BAX expression (p=0.043) and pathologic stage (p=0.05). BCL-2 immunostaining was inverse associated with tumor grade (p=0.008). Lack of BAX expression was related to reduced patient's survival (p=0.028). Mortality was higher in patients with BCL-2+/TP53+ (p=0.023) or TP53+/BAX- (p=0.027) phenotype. BAX and pathologic stage were independent predictors of progression-free and overall survival, respectively. Therefore, BAX expression might be relevant in patient's prognosis.

Adult↗
PubMed2006

Alpha-methylacyl-CoA racemase (P504S)/34betaE12/p63 triple cocktail stain in prostatic adenocarcinoma after hormonal therapy.

Alpha-methylacyl-CoA racemase (AMACR) has recently been shown to be a highly sensitive marker for the diagnosis of prostate cancer. However, there is limited information concerning its utility as a marker for prostate carcinoma after hormonal therapy. Our current investigation was conducted to evaluate the expression of AMACR in patients with prostate carcinoma after hormonal therapy and assess its diagnostic utility in combination with p63 and high molecular weight cytokeratin (34betaE12) staining. Prostate tissues from 49 patients who had been treated with hormonal therapy were immunohistochemically analyzed for AMACR, 34betaE12, and p63 expression by a triple antibody cocktail stain. The staining intensities and the percentages of positively staining tumor cells were recorded. The correlations between AMACR expression and metastatic status, associated hormonal therapy regimens, and the extent of hormone therapy effect were analyzed. All malignant acini were completely negative for both basal cell markers (34betaE12 and p63). Tumor cells failed to demonstrate expression of AMACR in 14 (29%) of 49 cases. In the remaining 35 cases (71%), positive immunostaining for AMACR was noted, but with variable intensities and percentages of cells stained. Positive staining for AMACR in benign glands was not seen in any case. In all cases, basal cells were strongly stained by p63 in benign acini with a mean positive percentage of 96%. Similarly, basal cells in benign acini displayed moderate staining intensities for 34betaE12 in 3 (7%) of 41 cases and strong immunostaining for this marker in the remaining 38 cases (93%); the mean percentage of positive cells was 92%. alpha-methylacyl-CoA racemase expression may be substantially diminished or entirely lost in prostate carcinoma after hormonal therapy. This variation in AMACR expression does not correlate with the metastatic status, the modality of hormonal therapy, or the extent of therapy-related effect. It is important that pathologists be aware that some hormonally treated prostate carcinomas do not express AMACR, and that immunostaining in such cases must be interpreted with caution. A triple cocktail stain using AMACR, 34betaE12, and p63 can be helpful in evaluating prostate specimens for the presence of residual or recurrent carcinoma after hormonal therapy for cancer.

Adenocarcinoma↗
PubMed2006

Divergent pathway of intestinal metaplasia and cystitis glandularis of the urinary bladder.

Intestinal metaplasia has been proposed to be a precursor lesion of adenocarcinoma in the urinary bladder. CDX2 is a transcription factor that is encoded by a homeotype gene that plays an essential role in the differentiation and proliferation of intestinal epithelial cells. Hepatocyte-specific antigen (Hep) has also been shown to be a useful marker of intestinal metaplasia. Tissues from 46 patients, including 22 cases of intestinal metaplasia of the urinary bladder, 11 cases of typical cystitis glandularis, and 13 cases containing both lesions, were selected and immunohistochemical stains for CDX2, Hep, cytokeratin 20 (CK20), and cytokeratin 7 (CK7) were performed. Nuclear staining for CDX2 was observed in 29 of 35 (83%) cases of intestinal metaplasia of the urinary bladder. In contrast, nuclear staining for CDX2 was not observed in any case of typical cystitis glandularis; however, seven of 24 (29%) cases showed aberrant cytoplasmic expression in a mean of 37% of cells. CK20 was expressed in 28 of 35 (80%) cases of intestinal metaplasia, but was observed in only one of 24 (4%) cases of cystitis glandularis in 15% of cells. CK7 was expressed in only six of 35 (17%) cases of intestinal metaplasia, whereas expression of CK7 was observed in all cases (100%) of typical cystitis glandularis with a mean percentage of positively staining cells of 63%. The mean percentages of positively staining cells in intestinal metaplasia with CDX2, CK20, and CK7 were 55, 49, and 53%, respectively. All examples of both intestinal metaplasia and typical cystitis glandularis were uniformly negative for Hep. In the urinary bladder, intestinal metaplasia and typical cystitis glandularis have sharply contrasting immunoprofiles. Additionally, the absence of Hep staining in intestinal metaplasia of the urinary bladder, despite its morphologic resemblance to normal colonic mucosa and intestinal metaplasia in other organs, may signify the presence of unique metaplastic pathways in the urinary bladder.

Autoantigens↗
PubMed2006

Atypical foci suspicious but not diagnostic of malignancy in prostate needle biopsies (also referred to as "atypical small acinar proliferation suspicious for but not diagnostic of malignancy").

OBJECTIVE: To review atypical focus suspicious but not diagnostic of malignancy in needle biopsies of the prostate, also referred to as "atypical small acinar proliferation suspicious for but not diagnostic of malignancy." METHODS: A number of descriptive and somewhat confusing terms have been used to refer to a prostate tissue biopsy with small focus of atypical glands. Based on MEDLINE database searches, all aspects, including the synonymous terms, of atypical focus suspicious but not diagnostic of malignancy were examined. RESULTS: An average of 5% of needle biopsy pathology reports show a diagnosis of atypical focus suspicious for malignancy. It may be composed of acini of small size, that is, smaller than normal ducts and acini, but may also include glands with a diameter similar to that of normal ducts and acini. It encompasses a variety of lesions, including benign mimickers of cancer and small foci of carcinoma that, for a variety of reasons, cannot be accurately diagnosed. Maximal diagnostic information should be gained on section stained with haematoxylin and eosin, with immunohistochemical stains used for confirmation. Its presence in a biopsy set is a strong predictor for concurrent or subsequent adenocarcinoma. The values range from 17% to 60%, the mean being 40.7%. The precise labelling of the initial biopsies is mandatory so that rebiopsy of patients with atypical foci can be directed in a more concentrated fashion into the region of the initial biopsy. CONCLUSION: The presence of atypical focus suspicious but not diagnostic of malignancy in needle biopsies is an important predictor of cancer compared with biopsies from patients who lack this finding.

Biopsy, Needle↗
PubMed2006

Squamous differentiation in primary urothelial carcinoma of the urinary tract as seen by MAC387 immunohistochemistry.

Squamous differentiation (SqD) is variably present in urinary tract tumours, but its significance remains unclear. In this study, SqD was assessed by immunohistochemistry using the monoclonal antibody Mac387 in 145 urothelial tumours (bladder, n = 115; renal pelvis, n = 30). Mac387 detects the myelomonocytic L1 antigen; a member of the calgranulin family shared by epithelial cells and keratinocytes. L1 antigen was shown in SqD in urothelial carcinomas of the bladder or the renal pelvis, including 11 cases with focal SqD unrecognised by conventional analysis. SqD is more frequent in renal pelvic tumours (p = 0.027) and increases with grade/stage mainly in bladder carcinoma (grade, p = 0.05; stage, p = 0.005). Stage Ta/T1 bladder carcinomas with SqD recurred more (p = 0.021). In conclusion, Mac387 efficiently shows SqD in urothelial tumours.

Aged↗
PubMed2006

Bicalutamide 50 mg monotherapy in patients with isolated high-grade PIN: findings in repeat biopsies at 6 months.

OBJECTIVES: To evaluate morphological findings in repeat biopsies in patients with isolated high-grade prostatic intraepithelial neoplasia (HGPIN) after a 6-month course of bicalutamide (Casodex) 50 mg/day. METHODS: 20 consecutive patients with isolated HGPIN in prostate biopsies were treated for 6 months with bicalutamide 50 mg/day. After treatment, the patients were resubmitted to prostate biopsy mapping. The control group included 22 untreated consecutive patients with isolated high-grade PIN with repeat biopsies taken 6 months after the initial biopsies. RESULTS: In the initial biopsies of the treated group, HGPIN was monofocal in 12 patients and plurifocal in 8. In the repeat biopsies HGPIN was present in 2 patients, monofocal in both, whereas prostate adenocarcinoma (PCa) was discovered in one. In the control group, HGPIN was monofocal in 15 and plurifocal in 7. In the repeat biopsies HGPIN was present in six patients, being monofocal in three and plurifocal in the other three. PCa was present in one. CONCLUSIONS: There was a lower incidence of HGPIN (treated group vs control: 10% vs 27.2%) after 6 months of bicalutamide. Reduction in its extent was also observed (treated group vs control: monofocal 100% vs 50%). Treatment did not affect the incidence of cancer (treated vs control: 5% vs 4.5%).

Aged↗
PubMed2006

HER2 expression and gene amplification in pT2a Gleason score 6 prostate cancer incidentally detected in cystoprostatectomies: comparison with clinically detected androgen-dependent and androgen-independent cancer.

Previous studies have demonstrated HER2 protein overexpression and/or gene amplification in a subset of patients with clinically significant prostate cancer (PCa), especially in the androgen-independent phase of the disease. There are no studies on incidentally detected PCa. The aim of the study was to analyze HER2 expression and gene amplification in PCa incidentally detected in cystoprostatectomies. High-grade prostatic intraepithelial neoplasia (HGPIN) was also investigated. Comparison was made with clinically detected PCa, both untreated and hormonally treated, and with androgen-independent PCa. Nineteen cystoprostatectomy (CyP) and 44 radical prostatectomy specimens (25 untreated and 19 hormonally treated) with pT2a Gleason score 6 cancer and HGPIN were used in this study. It also included 9 specimens of transurethral resection of the prostate with hormone-independent cancer and 8 cases of normal prostate tissue from CyP specimens without PCa and prostatic intraepithelial neoplasia. HER2 protein and Ki-67 were investigated immunohistochemically. Patients with immunohistochemical scores of 2+ and 3+ were considered to have HER2 overexpression (HercepTest method). Dual-color fluorescence in situ hybridization analysis was performed using the CEP-17/HER dual probe combination. High-grade prostatic intraepithelial neoplasia showed HER2 overexpression in 26% of the CyP cases and in 40% and 83% of the untreated and treated cases, respectively. Prostate cancer showed HER2 overexpression in 16% of cases in the CyP group and in 36% and 47.5% in the untreated and treated groups, respectively. HER2 overexpression was present in 78% of androgen-independent cancers. HER2 gene amplification was seen in a small proportion of nuclei and some of the cases. In HGPIN, it ranged from 1.1% (in 5 cases) in the CyP group to 2.1% (in 10 cases) and 1.9% (in 6 cases) in the untreated and treated groups, respectively. In PCa, the proportion of nuclei with gene amplification was 0.7% (in 3 cases) in the CyP group, 2.6% (in 10 cases) and 2.5% (in 12 cases) in the untreated and treated groups, respectively, and 9% (in 6 cases) in the androgen-independent PCa. Ki-67 expression in HGPIN and PCa in CyP specimens was lower than in the radical prostatectomies and cases of transurethral resection of the prostate. Our findings in the current HER2-related study indicate that incidentally detected cancer has features of less aggressiveness than clinically detected cancer. This may contribute to a better understanding of the results obtained in screening programs where insignificant cancers are detected along with clinically significant cancers.

Adult↗
PubMed2006

Histopathology reporting of prostate needle biopsies. 2005 update.

This report reviews the diagnostic and prognostic importance of the pathologic findings in prostate needle biopsies. The morphological findings of the needle biopsy may be placed into one of the following five categories: prostate cancer, atypical small acinar proliferation, high-grade prostatic intraepithelial neoplasia, inflammation, and benign prostatic tissue. While the prime goal of the biopsy is to diagnose prostatic adenocarcinoma, once carcinoma is detected, further descriptive information regarding the type, amount of cancer, and grade forms the cornerstone for contemporary management of the patient and for assessment of the potential for local cure and the risk for distant metastasis. The information provided in the needle biopsy report regarding the attributes of carcinoma is used depending on the individual patient's medical condition and preference and on the treating physician's evaluation to determine whether any form of treatment is indicated and, if so, the type of therapy.

Adenocarcinoma↗
PubMed2006

Apoptotic and proliferation indexes in primary superficial bladder tumors.

Whether apoptotic index [AI] and/or Ki-67 labeling index [Ki-67LI] add prognostic information in bladder cancer remains unclear. Mean AI and Ki-67 LI increased with grade and stage in 147 superficial bladder tumors. AI (>1.7%) correlated with tumor size, grade and proliferation. Ki-67 LI (>10%) correlated with higher grade and stage. Tumor size and Ki-67 LI were independent predictors of disease-free and progression-free survival, respectively. Tumor size, patient's age and tumor's recurrence predicted overall survival. We conclude that conventional clinical parameters and Ki-67 LI define risk groups of bladder tumors, while AI has limited value.

Adult↗
PubMed2006

2004 WHO classification of the renal tumors of the adults.

BACKGROUND: The recently introduced 2004 World Health Organisation (WHO) classification of the adult renal epithelial neoplasms is meant to replace the previous 1998 WHO classification. METHODS AND RESULTS: The 2004 WHO classification is based on pathology and genetic abnormalities. The description of categories has been expanded to improve their recognition and new diagnostic categories are included. Emphasis has been placed on defining familial renal cancer, carcinoma associated with Xp11 translocations, carcinoma associated with neuroblastoma, multilocular cystic renal cell carcinoma, tubular, mucinous and spindle cells carcinoma; and mixed epithelial and stromal tumour. The potentially aggressive epithelioid angiomyolipoma is recognised. CONCLUSIONS: Recognising these categories may have important implications in patients' clinical management.

Adult↗
PubMed2006

2005 update on pathology of prostate biopsies with cancer.

OBJECTIVE: To review the diagnostic and prognostic importance of pathologic findings in prostate biopsies. MATERIALS AND RESULTS: While the primary goal of the biopsy is to diagnose prostatic adenocarcinoma, once carcinoma is detected, information regarding the type, amount, and grade of cancer forms the cornerstone for contemporary management of the patient and for assessment of the potential for local cure and the risk for distant metastasis. CONCLUSIONS: The novelty of this 2005 update is represented by a detailed morphologic and immunohistochemical description of prostatic adenocarcinoma features in biopsies.

Biopsy, Fine-Needle↗
PubMed2006

Pathological changes of high-grade prostatic intraepithelial neoplasia and prostate cancer after monotherapy with bicalutamide 150 mg.

OBJECTIVES: To evaluate the morphological changes induced by a 3-month course of neoadjuvant bicalutamide 150 mg/day before radical prostatectomy (RP) on prostatic adenocarcinoma and high-grade prostatic intraepithelial neoplasia (HGPIN). PATIENTS AND METHODS: In all, 90 patients with cT1-T2 prostate cancer and HGPIN on prostatic biopsy were randomized to receive bicalutamide (150 mg/day for 3 months) before RP, or to have immediate surgery. Surgical specimens were assessed for the histopathological features of cancer, HGPIN and benign epithelium in a blinded manner. The volumes of prostate cancer and HGPIN were evaluated using a stereological (i.e. grid) method. RESULTS: Compared with the bicalutamide-treated group, the ratio of stroma to epithelium, evaluated by visual microscopic assessment in the normal epithelium of the three prostate zones, was significantly lower in the control group, at 2.27 (sd 1.13), than in the treated group, at 1.87 (sd 0.72) (P = 0.048). The mean (sd) tumour volume was significantly lower in the bicalutamide-treated than in the control group, at 0.914 (0.13) vs 1.47 (0.24) mL (P = 0.044). Similarly, the mean (sd) volume of HGPIN was significantly lower in the bicalutamide-treated than in the control group, at 0.34 (0.06) vs 0.62 (0.07) mL (P = 0.003). At RP, specimen Gleason scores in the bicalutamide-treated group were similar to those in the control group, and were no different from the biopsy Gleason scores. CONCLUSIONS: Involution and epithelial shrinkage of prostate cancer and HGPIN were evident after neoadjuvant treatment with bicalutamide 150 mg. There was no evidence of the emergence of higher-grade cancer after treatment.

Adenocarcinoma↗
PubMed2006

A phase I-II preoperative biomarker trial of fenretinide in ascitic ovarian cancer.

PURPOSE: To evaluate study feasibility, toxicity, drug concentrations, and activity of escalating doses of the synthetic retinoid fenretinide [N-(4-hydroxyphenyl)retinamide (4-HPR)] in ovarian cancer by measuring serum CA125 and cytomorphometric biomarkers in cancer cells collected from ascitic fluid before and after treatment. METHODS: Twenty-two naive patients with ascitic ovarian cancer were treated with escalating doses of 4-HPR at 0, 400, 600, and 800 mg/d for 1 to 4 weeks before surgery. Changes in the proportion of proliferating cells expressed by Ki67 and computer-assisted cytomorphometric variables (nuclear area, DNA index, and chromatin texture) were determined in ascitic cells. Drug levels were measured by high-performance liquid chromatography. RESULTS: Doses up to 800 mg/d were well tolerated, and no adverse reactions occurred. There was no effect of 4-HPR on changes in serum CA125, Ki67 expression, which were assessed in 75% of subjects, and cytomorphometric variables, which were assessed in 80% of subjects. Plasma retinol levels were significantly lower in affected women than healthy donors. 4-HPR plasma concentrations increased slightly with increasing doses and attained a 1.4 micromol/L concentration with 800 mg/d. Drug levels in malignant ascitic cells and tumor tissue were higher than in plasma but were 50 and 5 times lower, respectively, than in carcinoma cells treated in vitro with 1 micromol/L 4-HPR. CONCLUSIONS: Cell biomarkers can be measured in ascitic cells to assess drug activity. Under our experimental conditions, 4-HPR did not show activity in advanced ovarian cancer cells. However, clinical evidence supports further investigation of fenretinide for ovarian cancer prevention.

Adult↗