Search PubMed⌕ Search

Biomedical subjects

V E Reuter

Publications and source records attributed to V E Reuter.

At least 19 recordsLinked to original sources

ADAM12 is highly expressed in carcinoma-associated stroma and is required for mouse prostate tumor progression.

The interaction between stromal cells and tumor cells is emerging as a critical aspect of tumor progression. Yet there is a paucity of molecular markers for cells participating in such interactions, and only few genes are known to play a critical role in this process. Here, we describe the identification of ADAM12 (a disintegrin and metalloprotease 12) as a novel marker for a subpopulation of stromal cells that are adjacent to epithelial tumor cells in three mouse carcinoma models (models for prostate, breast and colon cancer). Moreover, we show that ADAM12 is essential for tumor development and progression in the W10 mouse model for prostate cancer. These results suggest that ADAM12 might be a useful marker for stromal cells in mouse tumors that are likely to participate in stromal/tumor cell crosstalk, and that ADAM12 is a potential target for design of drugs that prevent carcinoma growth.

ADAM Proteins↗

Low-volume nodal metastases detected at retroperitoneal lymphadenectomy for testicular cancer: pattern and prognostic factors for relapse.

PURPOSE: To determine the incidence, pattern, and predictive factors for relapse in patients with low-volume nodal metastases (stage pN1) at retroperitoneal lymphadenectomy (RPLND) and identify who may benefit from chemotherapy in the adjuvant or primary setting. PATIENTS AND METHODS: Fifty-four patients with testicular nonseminomatous germ cell tumor had low-volume retroperitoneal metastases (pathologic stage pN1, 1997 tumor-node-metastasis classification) resected at RPLND, 50 of whom were managed expectantly without adjuvant chemotherapy. The dissection was bilateral in 12 and was a modified template in 38 patients. Retroperitoneal metastases were limited to microscopic nodal involvement in 14 patients. Follow-up ranged from 1 to 106 months (median, 31.4 months). RESULTS: Eleven patients (22%) suffered a relapse at a median follow-up of 1.8 months (range, 0.6 to 28 months). The most frequent form of recurrence was marker elevation in nine (18%) patients. Persistent marker elevation after orchiectomy and before retroperitoneal lymphadenectomy was a significant independent predictor of relapse (relative risk, 8.0; 95% confidence interval, 2.3 to 27.8; P =.001). Four of five (80%) patients with elevated markers (alpha-fetoprotein alone in three, alpha-fetoprotein and beta human chorionic gonadotropin in one) suffered a relapse, compared with seven of 45 (15.6%) patients with normal markers. CONCLUSION: Clinical stage I and IIA patients with normal markers who have low-volume nodal metastases have a low incidence of relapse and can be managed by observation only if compliance can be assured. In contrast, patients with elevated markers before retroperitoneal lymphadenectomy have a high rate of relapse and should be considered for primary chemotherapy.

Actuarial Analysis↗

ID gene expression varies with lineage during differentiation of pluripotential male germ cell tumor cell lines.

Human male germ cell tumors (GCTs) comprise an excellent model system for understanding the molecular events controlling cellular differentiation and lineage decision. Pluripotential embryonal carcinoma cell lines derived from GCTs can be induced to undergo terminal differentiation along specific lineages dependent upon the differentiating agent. We report here that one such cell line, NTera2/clone D1 (NT2/D1), previously shown to undergo differentiation along a neuronal lineage by all-trans-retinoic acid (RA), can be induced along a distinct non-neuronal lineage by the mammalian morphogens, bone morphogenetic proteins-2 and -4 (BMP-2 and -4). Very little is known regarding the molecular events that govern such human lineage decisions. In this study, the role of the ID (inhibitor of differentiation and DNA-binding) family of genes that act as inhibitors of the function of helix-loop-helix (HLH) transcriptional activators involved in lineage commitment was investigated using two pluripotential GCT cell lines as a model system. In the differetiation programs studied, Id1 was noted to decline, an event often associated with the decrease in proliferative rate occurring during differentiation. However, differences in the expression of ID2 and ID3 family members were detected between the programs. Notably, an increase in Id3 during RA-induced differentiation of NT2/D1 cells was observed, while Id2 levels increased during BMP-2 and -4 treatment of NT2/D1 cells and during the induction of an endodermal-like differentiation program in the cell line, 27X-1. The pluripotential male GCT cell lines comprise a unique system in which the roles of specific genes such as the ID family of genes in human cell differentiation and lineage decision can be studied.

Adult↗

Primary renal neoplasms with the ASPL-TFE3 gene fusion of alveolar soft part sarcoma: a distinctive tumor entity previously included among renal cell carcinomas of children and adolescents.

The unbalanced translocation, der(17)t(X;17)(p11.2;q25), is characteristic of alveolar soft part sarcoma (ASPS). We have recently shown that this translocation fuses the TFE3 transcription factor gene at Xp11.2 to ASPL, a novel gene at 17q25. We describe herein eight morphologically distinctive renal tumors occurring in young people that bear the identical ASPL-TFE3 fusion transcript as ASPS, with the distinction that the t(X;17) translocation is cytogenetically balanced in these renal tumors. A relationship between these renal tumors and ASPS was initially suggested by the cytogenetic finding of a balanced t(X;17)(p11.2;q25) in two of the cases, and the ASPL-TFE3 fusion transcripts were then confirmed by reverse transcriptase-polymerase chain reaction. The morphology of these eight ASPL-TFE3 fusion-positive renal tumors, although overlapping in some aspects that of classic ASPS, more closely resembles renal cell carcinoma (RCC), which was the a priori diagnosis in all cases. These tumors demonstrate nested and pseudopapillary patterns of growth, psammomatous calcifications, and epithelioid cells with abundant clear cytoplasm and well-defined cell borders. By immunohistochemistry, four tumors were negative for all epithelial markers tested, whereas four were focally positive for cytokeratin and two were reactive for epithelial membrane antigen (EMA) (one diffusely, one focally). Electron microscopy of six tumors demonstrated a combination of ASPS-like features (dense granules in four cases, rhomboid crystals in two cases) and epithelial features (cell junctions in six cases, microvilli and true glandular lumens in three cases). Overall, although seven of eight tumors demonstrated at least focal epithelial features by electron microscopy or immunohistochemistry, the degree and extent of epithelial differentiation was notably less than expected for typical RCC. We confirmed the balanced nature of the t(X;17) translocation by fluorescence in situ hybridization in all seven renal tumors thus analyzed, which contrasts sharply with the unbalanced nature of the translocation in ASPS. In summary, a subset of tumors previously considered to be RCC in young people are in fact genetically related to ASPS, although their distinctive morphological and genetic features justify their classification as a distinctive neoplastic entity. Finally, the finding of distinctive tumors being associated with balanced and unbalanced forms of the same translocation is to our knowledge, unprecedented.

Adolescent↗

Metastatic renal cell carcinoma neovasculature expresses prostate-specific membrane antigen.

OBJECTIVES: To determine whether the tumor-associated neovasculature of metastatic prostate and metastatic conventional (clear cell) renal carcinoma express prostate-specific membrane antigen (PSMA). PSMA is a type II integral membrane glycoprotein highly expressed in prostate cancer cells and also recently discovered to be expressed in the neovasculature of non-prostatic primary malignancies. METHODS: We examined metastatic prostate carcinoma (22 patients) and metastatic conventional (clear cell) renal carcinoma (20 patients) in various anatomic sites, including bone, lymph nodes, liver, lung, and soft tissue. Using the biotin-streptavidin method, we performed immunohistochemical reactions with the anti-PSMA monoclonal antibodies (mAbs) 7E11 and PM2J004.5 and with the anti-endothelial cell mAb CD34. RESULTS: Metastatic conventional (clear cell) renal carcinoma consistently expressed PSMA. The PM2J004.5 mAb was positive in 20 of 20 specimens, and the 7E11 mAb was positive in 15 of 20. The anti-PSMA immunoreactions with the neovasculature were confirmed by similar staining by the anti-CD34 mAb (20 of 20). Although the metastatic prostatic cancer cells expressed PSMA in all the specimens, only 2 of 22 had neovasculature PSMA expression. CONCLUSIONS: As in primary prostatic adenocarcinomas, the neovasculature of metastatic prostate cancer, regardless of site, rarely express PSMA. The neovascular endothelial cells of metastatic clear cell renal carcinoma, however, express PSMA. This expression may make PSMA an effective target for mAb-based antineovasculature therapy in metastatic renal carcinoma.

Adenocarcinoma, Clear Cell↗

Comparison of anti-prostate-specific membrane antigen antibodies and other immunomarkers in metastatic prostate carcinoma.

OBJECTIVES: To compare the immunohistochemical properties of the 7E11 anti-prostate-specific membrane antigen (anti-PSMA) monoclonal antibody (mAb) with the recently developed anti-PSMA mAb, PM2J004.5, and with other common immunomarkers in metastatic prostate cancer. PSMA is a type II integral membrane glycoprotein highly expressed in prostate cancer cells. The mAb 7E11 is currently used in the radioisotopic evaluation of prostate cancer, and its immunohistochemical properties have been examined in primary prostate cancer specimens. METHODS: We examined 23 formalin-fixed, paraffin-embedded, metastatic prostate carcinoma specimens from various anatomic sites, including bone, lymph node, liver, lung, and soft tissue. Using the biotin-streptavidin method, we performed immunohistochemical reactions with the anti-PSMA mAbs 7E11 and PM2J004.5 and with antibodies to prostate-specific antigen and prostatic acid phosphatase. The immunoreactions were scored by pathologists unaware of the clinical and pathologic data according to a staining intensity scale and the percentage of cells stained. RESULTS: All four mAbs consistently stained the metastatic prostate cancer specimens. In 2 (8.7%) of 23 cases, however, the prostate-specific antigen immunoreaction was negative but the anti-PSMA mAbs had positive staining. Although 7E11 and PM2J004.5 had a similar staining intensity and percentage of cells stained for most specimens, in 3 (13%) of 23 specimens, 7E11 had less intense staining. None of the specimens were negative for all four antibodies. CONCLUSIONS: Anti-PSMA mAbs consistently immunoreacted with metastatic prostate cancer specimens and were positive in instances when prostate-specific antigen staining was negative. The anti-PSMA mAbs demonstrated similar staining patterns; however, in select cases, the PM2J004.5 mAb did show more intense staining. The anti-PSMA mAbs 7E11 and PM2J004.5 are useful in the pathologic evaluation of paraffin-embedded metastatic prostate cancer specimens.

Antibodies, Monoclonal↗

Concurrent angiomyolipoma and renal cell neoplasia: a study of 36 cases.

Little is known about the association of angiomyolipoma and adult renal-cell neoplasia. We studied the clinicopathologic features of 36 patients with concurrent angiomyolipoma and renal-cell neoplasia from the consultation and surgical pathology files of nine institutions. HMB-45 immunoreactivity was analyzed in both neoplasms. Twenty-five sporadic cases of patients with angiomyolipoma and renal-cell neoplasia and 11 cases of patients with tuberous sclerosis, as defined by Gomez' criteria, had mean ages of 59 and 53 years, respectively, and female-male ratios of 2:1 and 5:1, respectively. The mean size of the angiomyolipomas was 1 cm in the sporadic cases and 3 cm in those patients with tuberous sclerosis (medians: 0.5 and 3 cm, respectively, P =.002). The mean sizes of the renal-cell neoplasms were 5 cm in sporadic cases and 6 cm in patients with tuberous sclerosis (medians: 4 and 5 cm, respectively; P =.88). In both clinical settings, angiomyolipoma was more commonly the incidental tumor. Clear-cell (conventional) renal-cell carcinoma was the most common renal-cell neoplasm in both groups of patients, accounting for approximately two thirds of the tumors. In patients with tuberous sclerosis, 27% of renal-cell neoplasms were oncocytomas, compared with 8% in sporadic cases (P =.15). Papillary neoplasia, chromophobe, and collecting-duct renal-cell carcinoma were found only in sporadic cases. All of the 22 renal-cell neoplasms studied were negative for HMB-45, whereas all 25 angiomyolipomas studied were positive.

Adenoma, Oxyphilic↗

Interobserver reproducibility of Gleason grading of prostatic carcinoma: urologic pathologists.

Gleason grading is now the most widely used grading system for prostatic carcinoma in the United States. However, there are only a few studies of the interobserver reproducibility of this system, and no extensive study of interobserver reproducibility among a large number of experienced urologic pathologists exists. Forty-six needle biopsies containing prostatic carcinoma were assigned Gleason scores by 10 urologic pathologists. The overall weighted kappa coefficient kappa(w) for Gleason score for each of the urologic pathologists compared with each of the remaining urologic pathologists ranged from 0.56 to 0.70, all but one being at least 0.60 (substantial agreement). The overall kappa coefficient kappa for each pathologist compared with the others for Gleason score groups 2-4, 5-6, 7, and 8-10 ranged from 0.47 to 0.64 (moderate-substantial agreement), only one less than 0.50. At least 70% of the urologic pathologists agreed on the Gleason grade group (2-4, 5-6, 7, 8-10) in 38 ("consensus" cases) of the 46 cases. The 8 "nonconsensus" cases included low-grade tumors, tumors with small cribriform proliferations, and tumors whose histology was on the border between Gleason patterns. Interobserver reproducibility of Gleason grading among urologic pathologists is in an acceptable range.

Humans↗

Expression of ID genes in differentiated elements of human male germ cell tumors.

The ID genes are members of a family of genes that encode helix-loop-helix (HLH)-containing proteins. The Id proteins, unlike other HLH proteins, lack an adjacent DNA binding domain and hence act as dominant negative regulators of HLH transcription factors that have been implicated in control of cellular differentiation. Although the role of Id genes in murine development has been documented, their roles in human embryogenesis remain unknown. In this study, human male germ cell tumors (GCTs) were used as a model for examining the expression of the ID genes in various histologies that are reflective of different temporal phases of human development. In seminomas, little or no expression of IDI, ID2, and ID3 was detected, consistent with the uncommitted germ cell-like phenotype of this tumor histology. Likewise, GCTs with histologies reflective of extraembryonic and embryonic patterns of differentiation exhibited patterns of expression of the three ID genes often similar to those noted during murine development. It was also evident, as revealed by ID expression patterns, that despite the overall aberrant spatial differentiation patterns displayed by these tumors, some tissue-tissue interactions reminiscent of those observed during normal embryogenesis are retained. Thus, adult male GCTs offer a unique system in which the role of genes such as the IDs can be studied in human embryogenesis.

Carcinoma, Embryonal↗

Mechanisms of prostatic stromal invasion in patients with bladder cancer: clinical significance.

PURPOSE: We assess the pathological mechanisms of silent prostatic stromal invasion in patients with bladder cancer for early detection and treatment. MATERIALS AND METHODS: Between August 1998 and January 1999, 10 patients with clinically organ confined transitional cell carcinoma of the bladder and known prostatic stromal invasion on transurethral biopsy or who were high risk for prostatic involvement due to tumor location near the bladder neck were studied for histological patterns of prostatic invasion. There were 5 cystectomy specimens distended for 24 hours with formalin via a Foley catheter, then step sectioned longitudinally at 3 mm. intervals through the bladder neck and prostate. Standard hematoxylin and eosin staining methods were used and sections were analyzed by 2 pathologists. RESULTS: There were 3 separate patterns of prostatic stromal invasion elucidated, including 2 previously described methods of extravesical or intraurethral invasion into the prostatic stroma and a third one through the bladder neck directly into the prostatic stroma. The third pattern was not grossly evident on endoscopy or urethral biopsy before cystectomy. CONCLUSIONS: Longitudinal sectioning of the bladder neck and prostate of cystectomy specimens suggests tumors at the bladder neck may directly invade the prostatic stroma without histological evidence of extravesical or intraurethral spread. Such direct silent tumor invasion of the prostate by superficial or endoscopically inapparent tumor is difficult to detect clinically by current biopsy methods. New methods of detection are necessary.

Carcinoma, Transitional Cell↗

Inverse associations between plasma lycopene and other carotenoids and prostate cancer.

Although dietary intake of tomatoes and tomato products containing lycopene has been reported to reduce the risk of prostate cancer, few studies have been done on the relationship between plasma lycopene and other carotenoids and prostate cancer. This case-control study was conducted to investigate the effects of plasma lycopene, other carotenoids, and retinol, as well as alpha- and gamma-tocopherols on the risk of prostate cancer. The study included 65 patients with prostate cancer and 132 cancer-free controls; all of them were interviewed using a standard epidemiological questionnaire at the Memorial Sloan-Kettering Cancer Center from 1993 to 1997. Plasma levels of carotenoids, retinol, and tocopherols were measured by high performance liquid chromatography. An unconditional logistic regression model was used in bivariate and multivariate analyses using Statistical Analysis System (SAS). After adjusting for age, race, years of education, daily caloric intake, pack-years of smoking, alcohol consumption, and family history of prostate cancer, significantly inverse associations with prostate cancer were observed with plasma concentrations of the following carotenoids: lycopene [odds ratio (OR), 0.17; 95% confidence interval (CI), 0.04-0.78; P for trend, 0.0052] and zeaxanthin (OR, 0.22; 95% CI, 0.06-0.83; P for trend, 0.0028) when comparing highest with lowest quartiles. Borderline associations were found for lutein (OR, 0.30; 95% CI, 0.09-1.03; P for trend, 0.0064) and beta-cryptoxanthin (OR, 0.31; 95% CI, 0.08-1.24; P for trend, 0.0666). No obvious associations were found for alpha- and beta-carotenes, retinol, and alpha- and gamma-tocopherols. Our study confirmed the inverse associations between lycopene, other carotenoids such as zeaxanthin, lutein, and beta-cryptoxanthin, and prostate cancer. This study provides justification for further research on the associations between lycopene and other antioxidants and the risk of prostate cancer.

Adult↗

High dose radiation delivered by intensity modulated conformal radiotherapy improves the outcome of localized prostate cancer.

PURPOSE: We present the long-term outcome and tolerance of 3-dimensional (D) conformal and intensity modulated radiation therapy for localized prostate cancer. MATERIALS AND METHODS: Between October 1988 and December 1998, 1,100 patients with clinical stages T1c-T3 prostate cancer were treated with 3-D conformal or intensity modulated radiation therapy. Patients were categorized into prognostic risk groups based on pretreatment prostate specific antigen (PSA), Gleason score and clinical stage. Sextant biopsies were performed 2.5 years or greater after treatment to assess local control. PSA relapse was defined according to the consensus guidelines of the American Society for Therapeutic Radiation Oncology. Late toxicity was classified according to the Radiation Therapy Oncology Group morbidity grading scale. Median followup was 60 months. RESULTS: At 5 years the PSA relapse-free survival rate in patients at favorable, intermediate and unfavorable risk was 85% (95% confidence interval [CI] +/- 4), 58% (95% CI +/- 6) and 38% (95% CI +/- 6), respectively (p <0.001). Radiation dose was the most powerful variable impacting PSA relapse-free survival in each prognostic risk group. The 5-year actuarial PSA relapse-free survival rate for patients at favorable risk who received 64.8 to 70.2 Gy. was 77% (95% CI +/- 8) compared to 90% (95% CI +/- 8) for those treated with 75.6 to 86.4 Gy. (p = 0.04) [corrected]. The corresponding rates were 50% (95% CI +/- 8) versus 70% (95% CI +/- 6) in intermediate risk cases (p = 0.001), and 21% (95% CI +/- 8) versus 47% (95% CI +/- 6) in unfavorable risk cases (p = 0.008) [corrected]. Only 4 of 41 patients (10%) who received 81 Gy. had a positive biopsy 2.5 years or greater after treatment compared with 27 of 119 (23%) after 75.6, 23 of 68 (34%) after 70.2 and 13 of 24 (54%) after 64.8 Gy. The incidence of toxicity after 3-D conformal radiation therapy was dose dependent. The 5-year actuarial rate of grade 2 rectal toxicity in patients who received 75.6 Gy. or greater was 14% (95% CI +/- 2) compared with 5% (95% CI +/- 2) in those treated at lower dose levels (p <0.001). Treatment with intensity modulated radiation therapy significantly decreased the incidence of late grade 2 rectal toxicity since the 3-year actuarial incidence in 189 cases managed by 81 Gy. was 2% (95% CI +/- 2) compared with 14% (95% CI +/- 2) in 61 managed by the same dose of 3-D conformal radiation therapy (p = 0.005). The 5-year actuarial rate of grade 2 urinary toxicity in patients who received 75.6 Gy. or greater 3-D conformal radiation therapy was 13% compared with 4% in those treated up to lower doses (p <0.001). Intensity modulated radiation therapy did not affect the incidence of urinary toxicity. CONCLUSIONS: Sophisticated conformal radiotherapy techniques with high dose 3-D conformal and intensity modulated radiation therapy improve the biochemical outcome in patients with favorable, intermediate and unfavorable risk prostate cancer. Intensity modulated radiation therapy is associated with minimal rectal and bladder toxicity, and, hence, represents the treatment delivery approach with the most favorable risk-to-benefit ratio.

Adenocarcinoma↗

Impact of separate versus en bloc pelvic lymph node dissection on the number of lymph nodes retrieved in cystectomy specimens.

PURPOSE: Pelvic lymphadenectomy during radical cystectomy yields a various number of lymph nodes depending on the extent of lymph node dissection and pathologist aggressiveness when searching the specimen. How the surgeon submits lymph nodes for pathological evaluation may also affect how many are retrieved. MATERIALS AND METHODS: Bilateral pelvic lymph node dissection and radical cystectomy for transitional cell carcinoma of the bladder was performed in 32 patients. The extent of lymph node dissection involved standard and extended lymphadenectomy in 20 and 12 cases, respectively. In patients who underwent standard dissection unilateral en bloc submission of the lymph nodes was done with the contralateral lymph node dissection sent as an individual discrete packet. In those who underwent extended dissection all lymph nodes from each side were submitted en bloc or as 6 packets. RESULTS: Standard lymphadenectomy en bloc specimens yielded a mean of 2.4 lymph nodes compared with 8.5 retrieved from individual lymph node specimens (p = 0.003). Extended lymphadenectomy en bloc specimens yielded a mean of 22.6 lymph nodes compared with 36.5 retrieved from the individually submitted packets (p = 0.02). CONCLUSIONS: Submitting pelvic lymph nodes as separate specimens optimizes pathological evaluation of the number of lymph nodes that may be involved with metastatic cancer. Such information is important for identifying patients who may benefit from adjuvant chemotherapy.

Cystectomy↗

Second primary malignancies associated with renal cell carcinoma: influence of histologic type.

OBJECTIVES: This study was performed to determine which histologic types of renal cell carcinoma have an association with a second primary malignancy. METHODS: Seven hundred sixty-three patients underwent an operation for renal cell carcinoma between July 1989 and January 1999. The incidence of antecedent, synchronous, or subsequent second malignancies was determined. Statistical tests based on the Poisson model were used to compare the observed number of subsequent malignancies developing after a diagnosis of renal cell carcinoma with the expected number calculated using the 1973 to 1994 U.S. Surveillance, Epidemiology, and End Results age, race, gender, and calendar-year specific incidence rates. RESULTS: Second primary malignancies were present in 209 of 763 (27.4%) patients, with prostate, breast, colon, and bladder cancer and non-Hodgkin's lymphoma being the five most common second malignancies. The other malignancies were antecedent in 118 cases (44.5%), synchronous in 104 cases (39.2%), and subsequent in 43 cases (16.2%). Patients with papillary renal cell carcinoma were at increased risk of developing bladder cancer (standardized incidence ratio [SIR] 6.5, P = 0.038). Men with papillary renal cell carcinoma were also at increased risk of developing prostate cancer (SIR 2.8, P = 0.035). CONCLUSIONS: There is an increased risk of subsequent bladder and prostate cancer in patients with papillary renal cell carcinoma.

Adolescent↗

Short term neoadjuvant androgen deprivation therapy does not affect prostate specific membrane antigen expression in prostate tissues.

BACKGROUND: Prostate specific membrane antigen (PSMA) is a transmembrane glycoprotein highly expressed in benign prostate secretory-acinar epithelium and prostate carcinoma. The results of several studies suggest that PSMA expression is increased in prostate carcinoma cell lines subjected to androgen deprivation and in androgen-independent tumors. The authors studied the effects of short term (3-month) androgen deprivation on PSMA expression in prostate carcinoma specimens using two anti-PSMA monoclonal antibodies (mAbs), 7E11 and PM2J004.5. METHODS: The study included patients with clinically localized prostate carcinoma who were prospectively randomized into 1 of 2 treatment groups: 3 months of neoadjuvant androgen deprivation therapy followed by radical prostatectomy (ADT/RP), or radical prostatectomy (RP) alone. Representative formalin fixed, paraffin embedded prostate sections were immunostained with the anti-PSMA mAbs 7E11 and PM2J004.5 by the streptavidin-biotin method. The authors recorded the staining intensity and the percentage of positive cells stained in benign epithelium, high grade prostatic intraepithelial neoplasia (PIN), and prostate carcinoma. They compared the results of 7E11 with those of PM2J004.5 in benign epithelium, high grade prostate, and carcinoma and also compared the results between the two treatment groups (ADT/RP vs. RP alone). RESULTS: Both anti-PSMA mAbs stained benign secretory-acinar epithelium, high grade PIN, and prostate carcinoma. In both treatment groups, PM2J004.5 reacted with a significantly greater percentage of cells (P < 0.001) and with significantly greater intensity (P < 0.001) compared with 7E11 in benign epithelium and prostate carcinoma. With both anti-PSMA mAbs, the percentage of cells stained and the intensity of staining in high grade PIN was similar to that in prostate carcinoma. In the group that received RP alone, the percentage of cells stained and the intensity of staining with 7E11 were significantly greater in high grade PIN and prostate carcinoma compared with benign epithelium (P < 0.001), and the intensity of staining with the PM2J004.5 was significantly greater in high grade PIN and prostate carcinoma compared with benign epithelium (P < 0.001). In the ADT/RP group, the percentage of cells stained and the intensity of staining with 7E11 and PM2J004.5 were significantly greater in prostate carcinoma compared with benign epithelium (P < 0.006). PSMA staining did not correlate with either Gleason score (in the group that received RP alone) or pathologic stage (in both the RP-alone and ADT/RP groups) and did not differ between the two treatment groups. CONCLUSIONS: Short term neoadjuvant ADT does not affect PSMA expression in benign prostate secretory-acinar epithelium, high grade PIN, or prostate carcinoma. Prostate carcinoma and high grade PIN express significantly higher levels of PSMA than benign prostate secretory-acinar epithelium. Compared with 7E11, the PM2J004.5 anti-PSMA mAb is a more sensitive immunohistochemical marker of prostate carcinoma in formalin fixed, paraffin embedded tissue.

Aged↗

Intrarenal schwannoma: a report of four cases including three cellular variants.

Renal schwannomas are extraordinarily rare neoplasms; only six have been reported, the majority of which occurred in the renal pelvis. We report the clinical and pathologic features of four additional cases. The resected kidney in all patients contained a well-demarcated, yellow-tan, smooth, and bulging intraparenchymal tumor (mean size, 9.7 cm; range, 4 to 16 cm). Microscopically, three cases were classified as cellular schwannomas, and one was a usual-type schwannoma, with degenerative nuclear atypia. By immunohistochemistry, all tumors were strongly S-100 protein positive and negative for pan-cytokeratin, CD57, smooth muscle actin, desmin, and CD34. Epithelial elements were not noted in the tumors, and there was no history of any clinical syndromes in these patients. Analysis of the four cases showed the mean age at presentation to be 47 years (range, 18 to 84 years), with no sex predisposition (two men, two women). Most patients were asymptomatic, and all received a diagnosis of renal cell carcinoma and treated as having such. Recognition and awareness of these rare, benign tumors will assist in the differential diagnosis of spindle cell tumors of the kidney and prevent their misdiagnosis as sarcomatoid carcinomas of the kidney or renal sarcomas. Our study, the largest series to date of renal schwannomas, demonstrates a predilection for the cellular variant in the kidney, documents that these tumors may present in the nonhilar region of the kidney, and provides clinical evidence of their benign biologic behavior.

Adolescent↗

Immunophenotype of high-grade prostatic adenocarcinoma and urothelial carcinoma.

Morphologic features alone can usually be used to distinguish prostatic adenocarcinoma and urothelial carcinoma of the urinary bladder. Poorly differentiated tumors, however, can occasionally have features of both neoplasms, making determination of site of origin difficult. No study has provided a panel of antibodies to assist in the distinction of these two tumors. For this study, 73 examples of moderately and poorly differentiated prostatic adenocarcinoma and 46 examples of high-grade urothelial carcinoma were obtained from radical resection specimens. Immunohistochemical studies were performed using the following panel of antibodies: cytokeratin (CK) 7, CK 20, 34betaE12, Leu M1, carcinoembryonic antigen (CEA)m, CEAp, p53, Leu 7, prostate-specific acid phosphatase (PSAP), prostate-specific antigen (PSA), and B72.3. Mucicarmine was also performed. Intermediate and high-grade prostatic carcinoma were compared and then high-grade prostatic carcinoma was compared with high-grade urothelial carcinoma. PSA and PSAP each stained 94% of prostatic adenocarcinomas, but no urothelial carcinomas. Leu 7 stained 94% of prostate and 17% of urothelial carcinomas. Over half of the urothelial carcinomas showed positivity for 34betaE12 (65%), as did two cases of prostatic carcinoma (6%). Eighty-three percent of urothelial carcinomas and 12% of prostatic adenocarcinomas stained with CK 7. Forty-one percent of urothelial carcinomas and 12% of prostatic carcinomas were reactive for CEAm, and p53 stained 33% and 3% of urothelial and prostatic adenocarcinomas, respectively. No significant difference was seen in the expression of CEAp, CK 20, B72.3, Leu M1, or mucicarmine between prostate and urothelial carcinoma. We propose a panel of six antibodies to assist in the distinction of high-grade prostatic adenocarcinoma from high grade urothelial carcinoma: PSA, PSAP, 34betaE12, Leu 7, CK 7, and p53. The first three antibodies should be used initially; if results are negative, the remaining antibodies may be employed.

Adenocarcinoma↗