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Biomedical subjects

L Cheng

Publications and source records attributed to L Cheng.

At least 73 records · Page 4Linked to original sources
PubMed2001

Effect of sea anemone toxin anthopleurin-Q on sodium current in guinea pig ventricular myocytes.

AIM: To investigate the effects of a sea anemone toxin anthopleurin-Q (AP-Q) isolated from Anthopleura xanthogrammica on sodium current (INa) in isolated guinea pig ventricular myocytes. METHODS: Single myocytes were dissociated by enzymatic dissociation method. INa was recorded using whole-cell patch-clamp technique. RESULTS: AP-Q (3 - 300 nmol/L) increased INa in a concentration-dependent manner. The EC50 value for increasing INa was 104 nmol/L (95 % confidence range: 78 - 130 nmol/L). AP-Q 300 nmol/L shifted the I-V curve to the leftward, changed the membrane potential of half maximal activation to more negative potential from (-36.3 +/- 2.3) mV to (-43 +/- 3) mV (n = 6, P < 0.01) and changed the membrane potential of half maximal inactivation to more positive potential from (-75 +/- 6) mV to (-59 +/- 5) mV (n = 6, P < 0.01). AP-Q 300 nmol/L shortened the half-recovery time of INa from (114 +/- 36) ms to (17 +/- 2) ms (n = 6, P < 0.01). The fast inactivation time constant (tauf) of INa was markedly increased by AP-Q 300 nmol/L. CONCLUSION: AP-Q has a stimulating effect on I(Na) with slowing the inactivation course of INa.

Animals↗
PubMed2001

Anti-Fas antibody induces apoptosis in cultured human renal interstitial fibroblasts.

OBJECTIVE: To detect if Fas is expressed in human renal interstitial fibroblasts (hRIFs) and apoptosis of hRIFs can be induced by specific anti-Fas antibody. METHODS: hRIFs were cultured from isolated papillae of human kidney, and identified by morphologic examination, assay of antigenic components and culture in D-valine selective medium. Fas expression in normal hRIFs was detected by RT-PCR and immunocytochemistry staining. After hRIFs were incubated with interferon gamma (gamma-IFN 500 U/ml, 1000 U/ml, 1500 U/ml and 2000 U/ml, respectively) for 48 hours, Fas expression was determined by Northern blot, Western blot and flow cytometry. hRIFs pre-stimulated with gamma-IFN (500 U/ml, 48 hours) were incubated with anti-Fas antibody (IgM, 0.5 microgram/ml) for 12 hours. And apoptosis was identified by morphologic examination, DNA ladder assay and flow cytometry. RESULTS: The cultured hRIFs showed a shuttle-like shape and were positively stained by labeled anti-vimentin antibody but negatively stained by anti-epithelial membrane antibody. They could not grow in the D-valine selective medium and died partly in a week. Fas mRNA and protein were expressed in normal hRIFs and markedly upregulated by stimulation with gamma-IFN. Apoptosis in gamma-IFN pre-stimulated hRIFs was induced by anti-Fas antibody, showing cell nuclear shrinkage and condensation in morphologic feature, internucleosomal DNA fragmentation in DNA ladder assay and a pick of hypo-diploid nuclei by flow cytometry. CONCLUSION: Fas is normally expressed in hRIFs and can be markedly upregulated by gamma-IFN. Anti-Fas antibodies can induce apoptosis of hRIFs pre-stimulated with gamma-IFN.

Antibodies, Monoclonal↗
PubMed2001

[Microscopic identification of Rhodiola henryi].

OBJECTIVE: To study the microscipic characteristics of the rhizoma, root, stem, leaf and powder of Rhodiola henryi. METHOD: By microscopic observation. RESULTS: The brown substance was always found in the rhizoma and root of Rhodiola henryi. There was a fiber ring in the cambium region of the stem, and some fiber bundles surrounded the pholem. The epidemis cells of the leaf were different in size, and some were very large. Most stomata were anisocytic. The pollen grains were spherical or oblate, with irregularly reticular veins on the outer walls and three germ pore furrows. CONCLUSION: The above-mentioned characteristics provided a basis for the identification of Rhodiola henryi.

Microscopy↗
PubMed2001

[Study on susceptibility test of pathogenic fungi from otorhinolaryngology by Etest method].

OBJECTIVE: To study the sensitivity of pathogenic fungi from otorhinolaryngology to 5 antifungal agents of Ketoconazole (KE), Itraconazole(IT), Fluorocytosine(FC), Amphtericin B (AP) and Fluconazole(FL) by Etest method. METHOD: Etest for determine MIC of 14 pathogenic fungi was performed according to the manufacturer's instructions. The Etest strip containing the 5 antifungal drugs were putted on medium with Candida albicans, A. flarus and A. fumigatus etc., respectively, to determine MIC of antifungal drugs. RESULT: Candida albicans were sensitized to all the above 5 antifungal drugs, KE and IT were most sensitized. Seven fungi such as A. flavus, A fumigatus, A. oryzae etc were all sensitized to KE and IT. The MIC range of KE and IT against 15 strains of pathogenic fungi were < or = 0.008-2 mg/L and < or = 0.006-4 mg/L respectively. In 15 strains, 11 strains showed drug-resistant to FL, 8 strains to AP and FC, 4 strains to KE and 1 strains to IT respectively and MIC were all > 32 mg/L. CONCLUSION: Etest MIC were in good agreement with macrobroth MIC. The use of Etest strips for antifungal susceptibility test is a new and promising method with advantage of easy to perform, exact results and satisfactory reproducibility. Etest is valuable on clinical practice.

Antifungal Agents↗
PubMed2001

[Studies on the triterpenoidal saponins from flowers of Eriobotrya japonica].

OBJECTIVE: To investigate the chemical composition of the flowers of Eriobotrya japonica. METHODS: Four constituents were isolated from the ethanolic extracts of flowers of Eriobotrya japonica (Thunb) Lindl and were identified by chemical methods and spectroscopic (IR, MS, 1HNMR, 13CNMR). RESULTS: The structures were identified as: Oleanolic acid (I), Ursolic acid(II), 2 alpha, 3 alpha, 19 alpha-Trihydroxyurs-5,12-dien-28-acid (III) and 2 beta, 3 beta, 23 alpha-Trihydroxyolean-12-en-28-acid (IV). CONCLUSION: The compounds I, II, III and IV were obtained from the flowers of Eriobotrya japonica for the first time.

Eriobotrya↗
PubMed2000

Proximity of prostate cancer to the urethra: implications for minimally invasive ablative therapies.

OBJECTIVES: The delivery of thermotherapy, cryotherapy, and interstitial radiation with minimal morbidity is dependent on the preservation of the prostatic urethra. Our aim was to determine the distribution of the distance between the urethra and the nearest prostate cancer. METHODS: We determined the location of cancer in 350 prostate cancers treated by radical prostatectomy between 1991 and 1993. Each pathologic specimen was totally embedded, serially sectioned, and whole mounted. For each prostate, the radial distance from the urethra to the nearest cancer was determined (urethral-cancer distance). The urethra-cancer distance was correlated with the clinical, pathologic, and laboratory factors. Univariate and multivariate associations with progression-free survival were determined. RESULTS: The mean follow-up was 6.1 years. Ninety-three patients had biochemical, local, or systemic cancer recurrence. The mean +/- SD distance from the urethra to the nearest cancer was 3 +/- 3 mm (range 0 to 18). In 58 patients (17%), the cancer touched the urethra. A decreasing urethra-cancer distance was associated with increasing rates of cancer recurrence (P = 0.009). The urethra-cancer distance correlated with each of the following preoperative factors: preoperative prostate-specific antigen (r = -0. 22, P <0.001), Gleason score in biopsy specimen (r = -0.13, P = 0.02), and percentage of Gleason score 4 or 5 in the biopsy specimen (r = -0.17, P = 0.008). CONCLUSIONS: The distance between the urethra and the nearest cancer was associated with prostate cancer outcome. Many patients have cancer close to the urethra. This finding may have implications for nonsurgical ablative therapies for prostate cancer.

Aged↗
PubMed2000

Repair of tobacco carcinogen-induced DNA adducts and lung cancer risk: a molecular epidemiologic study.

BACKGROUND: Only a fraction of cigarette smokers develop lung cancer, suggesting that people differ in their susceptibility to this disease. We investigated whether differences in DNA repair capacity (DRC) for repairing tobacco carcinogen-induced DNA damage are associated with differential susceptibility to lung cancer. METHODS: From August 1, 1995, through April 30, 1999, we conducted a hospital-based, case-control study of 316 newly diagnosed lung cancer patients and 316 cancer-free control subjects matched on age, sex, and smoking status. DRC was measured in cultured lymphocytes with the use of the host-cell reactivation assay with a reporter gene damaged by a known activated tobacco carcinogen, benzo[a]pyrene diol epoxide. Statistical tests were two-sided. RESULTS: Overall, lower DRC was observed in case patients than in control subjects (P:<.001) and was associated with a greater than twofold increased risk of lung cancer. Compared with the highest DRC quartile in the control subjects and after adjustment for age, sex, pack-years of smoking, family history of cancer, and other covariates, reduced DRC was associated with increased risk of lung cancer in a dose-dependent fashion (odds ratio [OR] = 1.8 with 95% confidence interval [CI] = 1.1-3.1, OR = 2.0 with 95% CI = 1.2-3.4, and OR = 4. 3 with 95% CI = 2.6-7.2 for the second, third, and fourth quartiles, respectively; P:(trend)<.001). Case patients who were younger at diagnosis (<60 years old), female, or lighter smokers or who reported a family history of cancer exhibited the lowest DRC and the highest lung cancer risk among their subgroups, suggesting that these subgroups may be especially susceptible to lung cancer. CONCLUSION: The results provide evidence that low DRC is associated with increased risk of lung cancer. The findings from this hospital-based, case-control study should be validated in prospective studies.

Age Factors↗
PubMed2000

The role of thymus-expressed chemokine and its receptor CCR9 on lymphocytes in the regional specialization of the mucosal immune system.

Chemokines play an important role in the migration of leukocytes at sites of inflammation, and some constitutively expressed chemokines may direct lymphocyte trafficking within lymphoid organs and peripheral tissues. Thymus-expressed chemokine (TECK or Ckbeta-15/CCL25), which signals through the chemokine receptor CCR9, is constitutively expressed in the thymus and small intestine but not colon, and chemoattracts a small fraction of PBLs that coexpress the integrin alpha(4)beta(7). Here we show that TECK is expressed in the human small bowel but not colon by endothelial cells and a subset of cells in intestinal crypts and lamina propria. CCR9 is expressed in the majority of freshly isolated small bowel lamina propria mononuclear cells (LPMC) and at significantly higher levels compared with colonic LPMC or PBL. TECK was selectively chemotactic for small bowel but not colonic LPMC in vitro. The TECK-induced chemotaxis was sensitive to pertussis toxin and partially inhibited by Abs to CCR9. TECK attracts predominantly the T cell fraction of small bowel LPMC, whereas sorted CD3(+)CCR9(+) and CD3(+)CCR9(-) lymphocytes produce similar Th1 or Th2 cytokines at the single cell level. Collectively, our data suggest that the selective expression of TECK in the small bowel underlie the homing of CCR9(+) intestinal memory T cells to the small bowel rather than to the colon. This regional specialization implies a segregation of small intestinal from colonic immune responses.

Cell Movement↗
PubMed2000

Cdk2-dependent phosphorylation and functional inactivation of the pRB-related p130 protein in pRB(-), p16INK4A(+) tumor cells.

The retinoblastoma family proteins pRB, p107, and p130 are phosphorylated and released from E2Fs in the late G(1) phase of the cell cycle. This phosphorylation is thought to contribute to the derepression of E2F-responsive genes and to be mediated, in part, by Cdk4 and Cdk6. Evidence that Cdk4/6 activity is inhibited by p16(INK4A) in most pRB(-) cells suggests that p107 and p130 may be underphosphorylated and remain associated with E2Fs during G(1)-S progression in cells that lack pRB. To examine this, we evaluated the cell cycle-dependent phosphorylation and E2F binding abilities of p107 and p130 in pRB(-), p16(+) Saos-2 osteosarcoma cells. p130, but not p107, was phosphorylated and released from E2F-4 in late G(1) and S phase cells, although p130 phosphorylation differed qualitatively in these and other pRB(-), p16(+) cells as compared with pRB(+), p16(-) cell types. p130 phosphorylation occurred in the absence of cyclin D-Cdk4/6 complexes, coincided with cyclin E- and Cdk2-associated kinase activity, and was prevented by expression of dominant negative Cdk2. Moreover, dominant negative Cdk2 prevented the dissociation of endogenous p130-E2F-4 complexes and inhibited E2F-4-dependent transcription. These findings show that p130 can be phosphorylated and functionally inactivated in a Cdk2-dependent process, and they highlight the involvement of distinct Cdks in the regulation of different pRB family proteins.

CDC2-CDC28 Kinases↗
PubMed2000

Predicting the survival of bladder carcinoma patients treated with radical cystectomy.

BACKGROUND: Clinical outcomes vary for patients treated with radical cystectomy. The authors sought to identify factors associated with the survival of patients treated with radical cystectomy for urothelial carcinoma of the urinary bladder. METHODS: The authors studied 218 patients treated with radical cystectomy for urothelial carcinoma between 1980 to 1984. Patient ages ranged from 41 to 78 years (mean, 64 years). Using the 1997 TNM system, T classifications were Ta (17 patients), T1 (44), T2 (71), T3a (42), T3b (14), T4a (28), and T4b (2). Thirty-two patients had lymph node metastasis at the time of surgery. Histologic grade was determined according to the newly proposed World Health Organization and International Society of Urological Pathology grading system; tumor was low grade in 43 patients and high grade in 175. The male-to-female ratio was 4.9 to 1. The mean follow-up of patients still alive was 13.1 years (median, 13.8 years; range, 30 days to 18 years). Cox proportional hazards models were used to determine the impact of numerous clinical and pathologic findings on survival. RESULTS: Ten-year local recurrence free, distant metastasis free, cancer specific, and all-cause survival were 71%, 73%, 67%, and 41%, respectively. In univariate analysis, cancer size, T classification, and lymph node status were associated with distant metastasis free, cancer specific, and all-cause survival. Histologic grade and surgical margin status were significantly associated with worse cancer specific and all-cause survival, but not with distant metastasis free survival. In multivariate analysis, cancer size, margin status, T classification, and lymph node status were identified as significantly associated with cancer specific survival after adjustment for age and gender. CONCLUSIONS: Long term survival is achieved in a significant number of patients treated with radical cystectomy. In this study, patients with organ-confined (< or = pT2) and small size (< or = 3 cm) cancer had favorable 10-year distant metastasis free (93%) and cancer specific survival (88%) after cystectomy. Tumor size, margin status, extravesical involvement, and lymph node metastasis are important pathologic factors and should be considered as stratification variables in identifying patients for whom adjuvant chemotherapy should be evaluated in clinical trials.

Adult↗
PubMed2000

Exogenous FGF-4 can suppress anterior development in the mouse embryo during neurulation and early organogenesis.

Members of the fibroblast growth factor (FGF) family of peptide growth factors are widely expressed in the germ layer derivatives during gastrulation and early organogenesis of the mouse. We have investigated the effect of administering recombinant FGF-4 in the late-primitive streak stage embryo to test if the patterning of the body plan may be influenced by this growth factor. Shortly after FGF treatment the embryonic tissues up-regulated the expression of Brachyury and the RTK signaling regulator Spry2, suggesting that FGF signaling was activated as an immediate response to exogenous FGF. Concomitantly, Hesx1 expression was suppressed in the prospective anterior region of the embryo. After 24 h of in vitro development, embryos displayed a dosage-related suppression of forebrain morphogenesis, disruption of the midbrain-hindbrain partition, and inhibition of the differentiation of the embryonic mesoderm. Overall, development of the anterior-posterior axis in the late gastrula is sensitive to the delivery of exogenous FGF-4. The early response associated with the expression of Spry2 suggests that the later phenotype observed could be primarily related to an inhibition of the FGF signaling pathway.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Molecular cloning and chromosomal mapping of a candidate cytokine gene selectively expressed in human CD34+ cells.

A rare population of human bone marrow (BM) and cord blood (CB) mononuclear cells bearing the CD34 surface marker (CD34+) function as hematopoietic stem/progenitor cells. Cells lacking CD34 expression (CD34-) in BM and CB are largely mature hematopoietic cells of various lineages that are derived from the CD34+ cells. To elucidate molecular mechanisms governing functional differences between CD34+ and CD34- hematopoietic cells, we used representational difference analysis (RDA)-based subtraction to identify genes that are specifically or preferentially expressed in CD34+ cells. Among the 73 RDA fragments initially sequenced, 30% are derived from the CD34 and c-kit genes that are preferentially expressed in CD34+ cells. An additional 27 (37%) are novel or homologous only to entries in expressed sequence tag databases. One (C17) was found four times and is expressed in CD34+ but not in CD34- cell populations from CB or BM. The cloned C17 cDNA encodes a novel polypeptide of 136 amino acids with a signal sequence. No homology to this peptide was found in the public databases. A secondary-structure analysis predicts that the C17 peptide contains four alpha-helices, a characteristic of hematopoietic cytokines and interleukins. This novel gene is mapped to human chromosome 4p15-p16.

Amino Acid Sequence↗
PubMed2000

Electrical Double-Layer Structure at the Rutile-Water Interface as Observed in Situ with Small-Period X-Ray Standing Waves.

X-Ray standing wave (XSW) measurements were made of Rb and Sr adsorbed from aqueous solutions at the rutile (110)-water interface. These experiments were performed to address the extent to which direct measurements of electrical double-layer structure are possible. The experimental results show that the Bragg XSW technique, using small-period standing waves generated by Bragg diffraction from the substrate, can precisely measure ion locations within the condensed layer and the in situ partitioning of ions between the condensed and diffuse layers. Differences in condensed layer ion positions were observed for Sr ions (measured in situ) as compared with Rb ions (in situ) and also for Sr ions (ex situ). An additional constraint on the ex situ Sr site geometry was provided by polarization-dependent surface EXAFS measurements. Such measurements can provide important constraints for the development and verification of electrical double-layer theory especially as applied to ion adsorption at the solid-water interface. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

Cancer heterogeneity and its biologic implications in the grading of urothelial carcinoma.

BACKGROUND: Urothelial carcinoma of the bladder often contains areas with different histologic grades. The influence of cancer heterogeneity on grading and its relation to patient outcome is uncertain. METHODS: The study group consisted of 164 patients with Ta urothelial carcinoma diagnosed at the Mayo Clinic between 1985 and 1986. None had previous or coexistent urothelial carcinoma in situ or invasive carcinoma. The primary (most common) and secondary (second most common if at least 5% of the cancer) patterns of cancer growth were graded by the newly proposed World Health Organization and International Society of Urological Pathology (WHO/ISUP) grading system. Scores of 1, 2, and 3 were assigned to urothelial neoplasms of low malignant potential (LMP), low grade urothelial carcinoma, and high grade urothelial carcinoma, respectively. The mean follow-up was 7.7 years (range, 0-13.3 years; median, 9.2 years). Progression was defined as the development of invasive carcinoma, distant metastasis, or death due to bladder carcinoma. RESULTS: Patient ages ranged from 36 to 96 years (mean, 69 years), and the male-to-female ratio was 4:1. Disease progression developed in 32 patients during a mean follow-up of 7.7 years. The mean interval from diagnosis to progression was 3.1 years (range, 0.01-8.7 years). Progression free survival was 82%, 77%, and 76% at 5, 7, and 10 years, respectively. Primary and secondary grades were different for 52 patients (32%). Based on the worst grade, 19 patients (12%) had urothelial neoplasms of low malignant potential (LMP), 92 (56%) had low grade carcinoma, and 53 (32%) had high grade carcinoma. Histologic grades based on worst, primary, secondary, and combined primary and secondary grades were all significant for predicting progression (P = 0.0009, 0.0004, 0.001, and 0.0001, respectively). Seven-year progression free survival rates for patients with LMP, low grade, and high grade carcinoma (based on worst grade) were 93%, 82%, and 61%, respectively; for patients with combined scores of 2, 3, 4, 5, and 6, survival rates were 93%, 80%, 82%, 68%, and 40%, respectively. The difference between patients with combined scores of 5 or 6 was statistically significant (P = 0.02). CONCLUSIONS: Histologic grade of urothelial carcinoma based on the newly proposed WHO/ISUP grading system stratifies patients into prognostically significant groups. Grading should also take cancer heterogeneity into consideration, and prognostic accuracy appears to be increased when the combined primary and secondary grades are applied. [See editorial counterpoint on pages 1509-12 and reply to counterpoint on pages 1513-6, this issue.]

Adult↗
PubMed2000

Squamous papilloma of the urinary tract is unrelated to condyloma acuminata.

BACKGROUND: To the authors' knowledge, there is no previous report of squamous papilloma of the urinary tract. It is uncertain whether there is a correlation between squamous papilloma, condyloma acuminatum, and verrucous carcinoma. METHODS: The authors evaluated the clinical and pathologic features of squamous papilloma (5 of the bladder, 2 of the urethra), condyloma acuminatum (3 cases), and verrucous carcinoma (3 cases) of the urinary bladder and performed human papillomavirus (HPV) DNA in situ hybridization studies to determine whether HPV was a common feature shared by these lesions. In addition, DNA ploidy evaluation by image cytometry and p53 immunohistochemical staining were performed. RESULTS: Squamous papilloma of the urinary tract occurred in elderly women and followed a benign clinical course with infrequent recurrence. All squamous papillomas were HPV DNA negative and DNA diploid with no or minimal p53 nuclear accumulation. Condyloma acuminata of the bladder contained HPV DNA, increased p53 protein expression, and aneuploid DNA content. All three cases of condyloma acuminata were associated with coexistent condylomata of the external genitalia, and two required pelvic exenteration for uncontrolled expansile growth. Verrucous carcinoma of the bladder occurred in elderly patients. All three cases of verrucous carcinoma were negative for HPV DNA and DNA aneuploid, and they exhibited consistent p53 expression. CONCLUSIONS: These data indicate that squamous papilloma is a distinct entity not related to condyloma or verrucous carcinoma. These lesions are benign, HPV DNA negative, DNA diploid, and they lack p53 overaccumulation.

Adult↗
PubMed2000

Paraganglioma of the urinary bladder: can biologic potential be predicted?

BACKGROUND: Paraganglioma of the urinary bladder is rarely encountered and its biologic behavior is uncertain. The authors sought to determine the prognostic factors that would predict patient outcome. METHODS: The Mayo Clinic experience over 53 years with paraganglioma of the bladder was reviewed. All histologic slides from 16 patients were reviewed by the authors. Eight cases were examined immunohistochemically with cytokeratin (AE1/3, cytokeratin 7, and cytokeratin 20), vimentin, S-100 protein, neuroendocrine markers (chromogranin, synaptophysin, and neuron specific enolase), p53 protein, and MIB-1. DNA ploidy was determined by digital image analysis in formalin fixed, paraffin embedded tissue. The mean follow-up was 6.3 years (range, 0.4-16.4 years). RESULTS: Paraganglioma usually occurred in young adult women (mean age, 45 years; range, 16-74 years). The male-to-female ratio was 1 to 3. The common symptoms and signs were hypertension and hematuria. The tumors were usually located intramurally in the lateral and posterior wall of the bladder and were multifocal in 3 cases (18%). Seven patients were treated by transurethral resection, eight by partial cystectomy, and one by radical cystectomy. T classification was T1 (1 patient), T2 (9 patients), T3 (2 patients), and T4b (4 patients). At the time of diagnosis, one patient had distant metastasis and one had regional lymph node metastasis. One patient developed metastasis 1 year after diagnosis and died of the disease 1.5 years later. None of the patients with T1 or T2 tumors had recurrence or tumor progression. All tumors were aneuploid. The mean MIB-1 labeling index was 1.5% (range, 0.03-7.0%). The tumor cells displayed immunoreactivity for S-100 protein and neuroendocrine markers and were negative for p53 (except 1 case) and cytokeratin. CONCLUSIONS: Paraganglioma of the urinary bladder occurs mostly in young adult women. Patients with tumor of advanced classification (>/=T3) are at risk of recurrence, metastasis, and dying of the disease, whereas patients in this study with T1 or T2 disease had favorable outcomes after complete tumor resection.

Adolescent↗
PubMed2000

Atypical nephrogenic metaplasia of the urinary tract: a precursor lesion?

BACKGROUND: Nephrogenic metaplasia with cytologic atypia (atypical nephrogenic metaplasia) is occasionally encountered and its biologic potential is uncertain. METHODS: The authors describe 18 cases of atypical nephrogenic metaplasia characterized by the presence of prominent cytologic atypia, including nuclear enlargement, nuclear hyperchromasia, and enlarged nucleoli. DNA ploidy analysis by digital image analysis and immunostaining for high-molecular-weight cytokeratin (34betaE12), cytokeratin 7, cytokeratin 20, carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), p53, and MIB-1 were performed in 9 cases. RESULTS: The mean patient age was 62 years (median, 65 years; range, 39-84 years). The male-to-female ratio was 2.6:1. Two patients had a history of noninvasive papillary urothelial carcinoma. The typical clinical presentation was hematuria (8 patients) and voiding symptoms (5 patients). Cystoscopic findings were suspicious for neoplasm in 7 of 13 cases. The neoplastic cells were positive for high-molecular-weight cytokeratin, cytokeratin 7, and EMA, and were usually negative for cytokeratin 20 and CEA. p53 nuclear accumulation and increased MIB-1 labeling index were seen in 4 cases. DNA ploidy analysis showed aneuploid pattern in 2 of 9 cases. The mean patient follow-up was 3.5 years (range, 0.5-10.6 years); 2 patients had recurrent nephrogenic metaplasia, and the remainder were alive without recurrence or urothelial carcinoma. CONCLUSIONS: Atypical nephrogenic metaplasia is benign; it occasionally displays substantial cytologic abnormalities of no apparent clinical significance. Awareness of the spectrum of cytologic changes within this entity is critical to prevent overdiagnosis of cancer and avoid unnecessary treatment. There is no direct evidence that links atypical nephrogenic metaplasia to cancer.

Adult↗