Immunohistochemical expression of PDGFR, VEGF-C, and proteins of the mToR pathway before and after androgen deprivation therapy in prostate carcinoma: significant decrease after treatment.

Targeted therapy in hormone refractory prostate cancer (HRPC) is currently under evaluation in many trials. The effect of androgen deprivation therapy (ADT) on many targets in prostate cancer is incompletely known. For the first time, immunohistochemical expression of the platelet-derived growth factor receptor (PDGFR), epidermal growth factor receptor (EGFR), vascular endothelial growth factor C (VEGF-C), mammalian target of rapamycin (mToR), p70 ribosomal protein S6 kinase 1 (PS6K), human epidermal growth factor receptor 2 (c-erbB-2), and carbonic anhydrase IX (CA9) was evaluated in 44 patients with prostate carcinoma treated with or without ADT, at biopsy time and after radical prostatectomy. PDGFR, VEGF-C, mToR, and PS6K expression was significantly reduced (p = 0.002, p = 0.035, p = 0.025, and p = 0.033, respectively) after ADT, whereas expression of EGFR, c-erbB-2, and CA9 was not influenced by ADT. In conclusion, targeting PDGFR, VEGF-C, mToR, or PS6K after ADT should be considered with precaution, as those targets can severely be altered or functionally deregulated by ADT.

Quantification of extraprostatic perineural spread and its prognostic value in pT3a pN0 M0 R0 prostate cancer patients.

BACKGROUND: The prognostic relevance of the amount of extraprostatic cancer spread in nerves in prostate cancer patients is not well established. METHODS: Eighty-eight patients were included in our study with pT3a pN0 M0 R0 prostate cancer treated with retropubic prostatectomy. Eighty-seven of them showed perineural invasion, 54 were confined to the prostate, 33 showed cancer spread in extraprostatic nerves, which was quantified by counting each transverse section of nerves infiltrated by cancer in totally embedded specimens. Biochemical relapse was established by serum PSA levels of ≥0.2 ng/ml as well as PSA ≥ 0.4 ng/ml and higher according to the EAU guidelines. RESULTS: Extraprostatic but not intraprostatic perineural infiltration was significantly more often found in tumors of higher Gleason score. Intraprostatic number of infiltrated nerves (NIN) correlated with extraprostatic NIN. There was no association between extraprostatic or intraprostatic NIN and Gleason score, lymphatic, or blood vessel invasion. Extraprostatic neural infiltration in ≤10 nerves extended relapse free survival in univariate analysis for PSA 0.2 and 0.4 ng/ml (P = 0.002 and P < 0.000001, respectively) and remained significant in multivariate analysis for PSA 0.4 ng/ml (P = 0.039). CONCLUSIONS: High amount of extraprostatic NIN correlates with tumor progression and seems to be an independent prognostic parameter.

Expression of secretagogin in clear-cell renal cell carcinomas is associated with a high metastasis rate.

Renal cell carcinomas are divided into several subgroups according to their histopathologic characteristics. The outcome, therapy responses, and the applicability of molecular-targeted therapies depend on the tumor classification and on the tumor stage. Recent advances within the biomarker research facilitated the exact classification of the molecular character of the renal tumor. For example, the calcium-binding proteins parvalbumin and S-100A1 are characteristically expressed in renal cell carcinoma subgroups. This led us to investigate the expression of the novel calcium-binding protein secretagogin in renal cell carcinomas. Tissue microarray cylinders including 94 clear-cell renal cell carcinomas, 61 non-clear-cell renal cell carcinomas (37 papillary renal cell and 24 chromophobe carcinomas), and 30 oncocytomas were analyzed by immunohistochemistry. This showed remarkable secretagogin expression in 37% of the clear-cell renal cell carcinomas. Non-clear-cell renal cell carcinomas and oncocytomas were completely negative. Consequently performed immunoblotting analyses confirmed this expression profile. Because publicly available data direct toward a formation of a hierarchical cluster of secretagogin overexpressing clear-cell renal cell carcinomas, we conducted a clinical follow-up of the patients with clear-cell renal cell carcinoma. This revealed significantly more metastasis within the secretagogin-positive clear-cell renal cell carcinoma subgroup (49% versus 28%; P < .05). In conclusion, we report on detection of the novel calcium-binding protein secretagogin within a subgroup of clear-cell renal cell carcinomas. The increased metastasis rates within the secretagogin-positive subgroup of clear-cell renal cell carcinomas direct toward a clinical impact of our findings.

Expression of platelet-derived growth factor-alpha receptor in human osteosarcoma is not a predictor of outcome.

AIMS: The aims of this study were to examine the prognostic relevance of platelet-derived growth factor-α receptor (PDGFRA) expression in human osteosarcomas and to evaluate the mutation status of exon 12 and exon 18 of the PDGFRA gene. METHODS: PDGFRA expression was examined in 100 human osteosarcomas by immunohistochemistry using paraffin embedded tumour tissues, and capillary sequencing of genomic DNA was performed to search for mutations in exons 12 and 18 of the PDGFRA gene. RESULTS: Ninety-six osteosarcomas showed PDGFRA expression ranging from 4% to 90% (mean 40%, median 37.5%, SD 27.11%). Furthermore, DNA sequence of exon 12 and exon 18 of the PDGFRA gene were not altered in 40 tumours with high PDGFRA expression. Overall and disease-free survival analysis did not reveal any differences between osteosarcoma patients with high PDGFRA expression and patients with low PDGFRA expression. CONCLUSIONS: The protein expression is not linked to mutations in exon 12 or exon 18 of PDGFRA gene. Therefore, treatment modalities based on the suppression of PDGFRA tyrosine kinase activity may need further investigation. PDGFRA expression is not a prognostic marker for osteosarcoma patients.

Expression of platelet-derived growth factor-alpha receptor and c-kit in giant cell tumours of bone.

AIMS: Platelet-derived growth factor-alpha receptor (PDGFRA) and c-kit are tyrosine kinase receptors expressed in many neoplasms. We investigated protein expression in 34 giant cell tumours of bone and two specimens of lung metastases. METHODS: The expression of PDGFRA and c-kit was analysed by immunohistochemistry. Additionally, capillary sequencing of genomic DNA was performed to search for mutations in therapeutically relevant exons 12 and 18 of the PDGFRA gene and exons 9 and 11 of the c-kit gene. RESULTS: PDGFRA expression was detected in all specimens and all cellular components such as reactive osteoclast-like giant cells and neoplastic stromal cells. C-kit expression was found in six cases of giant cell tumour and one specimen of lung metastasis in all cellular components ranging from 5 to 50% (mean 4.8%, SD 12.4). A further 13 cases showed labelling of osteoclast-like giant cells. DNA sequence of exons 12 and 18 of the PDGFRA gene and exons 9 and 11 of the c-kit gene were not altered in these tumours. CONCLUSION: PDGFRA and c-kit play a functional role in the growth of giant cell tumours of bone but genetic changes of therapeutically relevant exons of the PDGFRA gene and the c-kit gene are not seen in these tumours.

Expression of platelet-derived growth factor-AA and platelet-derived growth factor-alpha receptor in ameloblastomas.

BACKGROUND: Platelet-derived growth factor (PDGF)-AA isoform and its receptor, PDGF-alpha receptor (PDGFRA) regulate tooth development and growth. We investigated the expression of both proteins in ameloblastomas, to contribute the understanding of the potential role of the PDGF/PDGFR system in this odontogenic neoplasm. METHOD: Twenty-nine specimens of ameloblastoma were analyzed for PDGF-AA and PDGFRA expression using immunohistochemistry. The proliferation activity was investigated with the MIB-1 antibody. Additionally, capillary sequencing of genomic DNA was performed to search for mutations in therapeutically relevant exons 12 and 18 of the PDGFRA gene. RESULTS: PDGF-AA and PDGFRA expression were detectable in all cases with the exception of one tumor. However, protein expression levels did neither correlate with each other nor with MIB-1 expression. Unicystic ameloblastomas did not differ from solid tumors with regard to PDGF-AA, PDGFRA, and MIB-1 expression. One tumor revealed a somatic mutation of exon 12 of the PDGFRA gene. CONCLUSION: PDGF-AA and PDGFRA proteins are regularly expressed in variable levels in ameloblastomas, and somatic mutations of exon 12 and exon 18 of the PDGFRA gene are rare findings.

The dielectric properties of human pineal gland tissue and RF absorption due to wireless communication devices in the frequency range 400-1850 MHz.

In order to enable a detailed analysis of radio frequency (RF) absorption in the human pineal gland, the dielectric properties of a sample of 20 freshly removed pineal glands were measured less than 20 h after death. Furthermore, a corresponding high resolution numerical model of the brain region surrounding the pineal gland was developed, based on a real human tissue sample. After inserting this model into a commercially available numerical head model, FDTD-based computations for exposure scenarios with generic models of handheld devices operated close to the head in the frequency range 400-1850 MHz were carried out. For typical output power values of real handheld mobile communication devices, the obtained results showed only very small amounts of absorbed RF power in the pineal gland when compared to SAR limits according to international safety standards. The highest absorption was found for the 400 MHz irradiation. In this case the RF power absorbed inside the pineal gland (organ mass 96 mg) was as low as 11 microW, when considering a device of 500 mW output power operated close to the ear. For typical mobile phone frequencies (900 MHz and 1850 MHz) and output power values (250 mW and 125 mW) the corresponding values of absorbed RF power in the pineal gland were found to be lower by a factor of 4.2 and 36, respectively. These results indicate that temperature-related biologically relevant effects on the pineal gland induced by the RF emissions of typical handheld mobile communication devices are unlikely.

High-resolution numerical model of the middle and inner ear for a detailed analysis of radio frequency absorption.

In order to enable a detailed analysis of radio frequency (RF) absorption in the human middle and inner ear organs, a numerical model of these organs was developed at a spatial resolution of 0.1 mm, based on a real human tissue sample. The dielectric properties of the liquids (perilymph and endolymph) inside the bony labyrinth were measured on samples of ten freshly deceased humans. After inserting this model into a commercially available numerical head model, FDTD-based computations for exposure scenarios with generic models of handheld devices operated close to the head in the frequency range 400-3700 MHz were carried out. For typical output power values of real handheld mobile communication devices the obtained results showed only very small amounts of absorbed RF power in the middle and inner ear organs. Highest absorption in the middle and inner ear was found for the 400 MHz irradiation. In this case, the RF power absorbed inside the labyrinth and the vestibulocochlear nerve was as low as 166 microW and 12 microW, respectively, when considering a device of 500 mW output power operated close to the ear. For typical mobile phone frequencies (900 MHz and 1850 MHz) and output power values (250 mW and 125 mW) the corresponding values of absorbed RF power were found to be more than one order of magnitude lower than the values given above. These results indicate that temperature-related biologically relevant effects on the middle and inner ear, induced by the RF emissions of typical handheld mobile communication devices, are unlikely.

Expression of c-kit in human osteosarcoma and its relevance as a prognostic marker.

AIMS: To examine the prognostic relevance of c-kit expression in human osteosarcomas and to evaluate the mutation status in exon 9 and exon 11 of the c-kit gene. METHODS: c-kit expression was examined in 100 human osteosarcomas by immunohistochemistry using paraffin embedded tumour tissues, and capillary sequencing of genomic DNA was performed to search for mutations in exons 9 and 11 of the c-kit gene. RESULTS: 20 osteosarcomas showed c-kit expression ranging from 5% to 90% (mean 5.9%; SD 16.74%). Furthermore, DNA sequences of exon 9 and exon 11 of the c-kit gene were not altered in these tumours. Overall and disease free survival analysis did not reveal any differences between patients with osteosarcoma with c-kit expression and those with c-kit negative tumours. CONCLUSIONS: C-kit expression is not a prognostic marker in patients with osteosarcoma. The protein expression is not linked to mutations in exon 9 or exon 11 of the c-kit gene. Therefore, these exons may not function as targets for treatment modalities based on the suppression of c-kit tyrosine kinase activity.

The changing distribution of pT stage in testicular germ cell tumours from 1976 to 2005: a single-centre analysis of histopathological reports.

OBJECTIVE: To assess the changing distribution of stage in seminoma and nonseminomatous germ cell tumours (NSGCTs), as recent reports contained no detailed information on pT stage and vascular invasion, important factors in the decision for further treatment. PATIENTS AND METHODS: Histopathological reports from 1976 to 2005, from patients who had surgery for testicular tumours at the authors' institution, were investigated with special focus on pT stage and its distribution. The whole study period was divided into six 5-year periods. The incidence of seminoma was compared with NSGCT, defined according to the Tumour-Nodes-Metastasis (TNM) classification. RESULTS: In each 5-year period the median number of tumours treated surgically was 86; the distribution of seminomas and NSGCTs remained stable during the study period (P = 0.201). pT4 and pT3 tumours declined or disappeared in both histopathological groups, while pT2 and pT1 tumours increased during the study period. Since 1996-2000, pT1 tumours decreased, whereas pT2 tumours increased in seminomas (P = 0.085) and NSGCTs (P = 0.003). CONCLUSION: The incidence of seminoma and NSGCT has not changed over the last 30 years in Vienna. With the establishment of vascular invasion in the TNM classification in 1997, the incidence of pT1 decreased while that of pT2 increased. Since then, the incidence of pT1 tumours in seminomas was 45.8% and 29.1% in NSGCT. According to generally accepted treatment guidelines, these patients might need no adjuvant treatment after surgery.

Tissue reactions induced by different embolising agents in cerebral arteriovenous malformations: a histopathological follow-up.

AIMS: Comparative histopathological analysis was performed in 47 incompletely embolised and resected cerebral arteriovenous malformations (AVMs). METHODS: Thirty-three AVMs were embolised with n-butyl-cyanoacrylate (NBCA), four with iso-butyl-cyanoacrylate (IBCA), seven with polyvinyl alcohol particles (PVA), one with a fibrin mixture, one with silicon pellets, and one with microcatheter balloons. Maximum exposure time (MET) of the embolising agent (interval between embolisation and surgery) ranged from <24 hours to 80 months. All AVMs were investigated regarding angionecrosis, angiofibrosis, acute inflammation, chronic inflammation, foreign-body reactions, vascular calcification, blood admixture to embolising cast, and capillary recanalisation within the AVMs. These parameters were correlated with MET, comparing different embolising agents, age, and sex. RESULTS: A typical sequence of events depending on MET is observed in all embolised AVMs: acute inflammation with mural angionecrosis is soon replaced by prominent chronic granulomatous vasculitis, which remains stable and is detectable for a very long time, even in AVMs with a MET of more than 6 years. CONCLUSION: Capillary recanalisation is always present in incompletely embolised AVMs, detectable after 3 months of MET, irrespective of the embolising agent used. Age and sex does not influence pattern and time course of tissue lesions and recanalisation in incompletely embolised AVMs.

Lymphatic endothelial progenitor cells contribute to de novo lymphangiogenesis in human renal transplants.

De novo lymphangiogenesis influences the course of different human diseases as diverse as chronic renal transplant rejection and tumor metastasis. The cellular mechanisms of lymphangiogenesis in human diseases are currently unknown, and could involve division of local preexisting endothelial cells or incorporation of circulating progenitors. We analyzed renal tissues of individuals with gender-mismatched transplants who had transplant rejection and high rates of overall lymphatic endothelial proliferation as well as massive chronic inflammation. Donor-derived cells were detected by in situ hybridization of the Y chromosome. We compared these tissues with biopsies of essentially normal skin and intestine, and two rare carcinomas with low rates of lymphatic endothelial proliferation that were derived from individuals with gender-mismatched bone marrow transplants. Here, we provide evidence for the participation of recipient-derived lymphatic progenitor cells in renal transplants. In contrast, lymphatic vessels of normal tissues and those around post-transplant carcinomas did not incorporate donor-derived progenitors. This indicates a stepwise mechanism of inflammation-associated de novo lymphangiogenesis, implying that potential lymphatic progenitor cells derive from the circulation, transmigrate through the connective tissue stroma, presumably in the form of macrophages, and finally incorporate into the growing lymphatic vessel.

Diagnostic significance of aquaporin-1 in liver tumors.

The diagnostic utility of aquaporin (AQP)-1 in liver tumors was tested and compared with other well-established markers. In 30 cholangiocarcinomas (CCs), 20 hepatocellular carcinomas (HCCs), and 10 metastatic colorectal carcinomas (MCCs) of the liver, expression of AQP-1, CD10, cytokeratin (CK) 7, CK20, and polyclonal carcinoembryonic antigen (pCEA) was tested. In addition, staining patterns of CD10 and pCEA were analyzed. To compare the selectivity of AQP-1 and CK7 as possible markers for differentiated cholangiocytes, liver biopsies of cholestatic disease were also analyzed. Aquaporin-1 expression was found in 93% of all CCs compared with 0% of HCC (P < .000001) and with 30% of MCC (P < .01). CD10 was positive in 16.7% of CC compared with 40% of HCC (P < .04) and to 20% of MCC (not significant). Cytokeratin 7 was positive in 90% of CC compared with 10% of HCC (P < .00001) and with 20% of MCC (P < .0001). Cytokeratin 20 was positive in 90% of MCC compared with 16.7% of CC (P < .0001) and with 20% of HCC (P < .00001). Canalicular staining patterns of CD10 and pCEA were observed in HCC (100% and 89.5%, respectively) but typically not in CC (0% and 6.7%, respectively) and never in MCC. In cholestatic disease, AQP-1 was expressed in differentiated epithelial cells of the bile ducts, whereas CK7-positive hepatocytes of Rappaport zone 1 did not show any AQP-1 reactivity. Therefore, AQP-1 seems to be a highly selective marker for differentiated cholangiocytes and can be very helpful in the differential diagnosis of liver tumors.

Osteoclast-like giant cell tumor in mucinous cystadenocarcinoma of the pancreas: an immunohistochemical and molecular analysis.

Osteoclast-like giant cell tumors (OLGT) are rare neoplasms of the pancreas and mostly associated with ductal adenocarcinomas. In this report, we present the rare case of OLGT associated with mucinous cystadenocarcinoma (MCC). We investigated the expression profile of both tumors by methods of molecular biology and immunohistochemistry. The panel of markers included osteopontin, her2/neu, mismatch repair genes, K-ras, p53, E-cadherin, VEGF-C, and podoplanin. Osteopontin was expressed by the osteoclast-like giant cells but not by the mononuclear tumor cells of the OLGT. We detected an amplification and overexpression of her2/neu in the MCC but not in the OLGT. Although we observed an immunohistochemical expression of hMSH2 and hMLH1 in the OLGT, we were not able to confirm this result by western blot analysis. We also did not find any microsatellite instability (D2S123, BAT26). While mutation of K-ras codon 12 was found in both tumor components, there was wild-type DNA of p53. E-cadherin was expressed in MCC but not in OLGT. VEGF-C was only positive in osteoclast-like giant cells and some of the mononuclear cells of OLGT. The vessel-rich stroma of OLGT did not present any podoplanin-positive lymphatic vessel. The observation of our case and others in the published literature may indicate separating OLGT with undifferentiated carcinoma from OLGT with MCC for the better clinical outcome of the latter.

Expression of kidney-specific cadherin distinguishes chromophobe renal cell carcinoma from renal oncocytoma.

Distinguishing renal oncocytoma from chromophobe and other renal carcinomas is essential, considering their differing biological potentials. Although renal oncocytoma is considered a benign tumor, chromophobe renal cell carcinoma has potentially malignant biological behavior. The numerous reported studies on distinguishing these 2 entities have been based on morphological, histochemical, immunohistochemical, ultrastructural, and cytogenetic features. But none of these features has proven to be reliably specific, especially in tumors with overlapping phenotypes. We report a novel immunohistochemical approach based on the expression of a recently described kidney-specific cadherin (Ksp-cadherin) for the differential diagnosis of these 2 tumors. We compared Ksp-cadherin expression in 212 renal tumors, including 102 clear cell renal carcinomas, 46 papillary renal cell carcinomas, 30 chromophobe carcinomas, 3 collecting duct carcinomas, and 31 oncocytomas. In addition, we examined the expression of epithelial membrane antigen, vimentin, CK7, and Hale's colloidal iron staining. We found that chromophobe renal cell carcinomas consistently (96.7% of cases) demonstrated a distinctive membrane pattern of Ksp-cadherin expression, whereas renal oncocytomas (3.2%), clear cell renal cell carcinomas (0%), papillary renal cell carcinomas (2.2%), and collecting duct carcinomas (0%) usually did not express Ksp-cadherin. CK7 expression was found in 90.0%, 6.5%, 7.8%, 76.1%, and 33.3% of these tumor cases, respectively. Whereas CK7 was detected in different types of renal cell carcinomas, Ksp-cadherin was expressed almost exclusively in chromophobe renal cell carcinomas. Immunohistochemical analysis of Ksp-cadherin offers a fast, reliable approach for the distinguishing between renal oncocytoma and chromophobe renal cell carcinoma that is applicable for routine pathology laboratory studies without the need for time-consuming and costly ancillary studies.

Expression of aquaporins and PAX-2 compared to CD10 and cytokeratin 7 in renal neoplasms: a tissue microarray study.

Diagnostic use of antibodies against aquaporin water channel proteins and PAX-2, a nuclear transcription factor in renal development, was tested in 202 renal neoplasms, using tissue microarray technique. Immunohistochemistry for aquaporin-1, aquaporin-2, PAX-2, CD10, and cytokeratin 7 was performed on 102 clear cell renal cell carcinomas, 44 papillary renal cell carcinomas (among them 34 type 1 and 10 type 2), 24 chromophobe renal cell carcinomas, three collecting duct carcinomas (carcinomas of the collecting ducts of Bellini), and 29 oncocytomas. Aquaporin-1 expression was found in clear cell renal cell carcinomas and papillary renal cell carcinomas of both types (78 and 73%, respectively), but not in chromophobe renal cell carcinomas, collecting duct carcinomas, and oncocytomas. Aquaporin-2 expression was not seen in any of the tested tumors. PAX-2 and CD10 was found in the majority of clear cell renal cell carcinomas (88 and 85%, respectively) but only in few papillary renal cell carcinomas, chromophobe renal cell carcinomas and oncocytomas. Decrease or loss of aquaporin-1 and PAX-2 was shown in higher grades compared to lower grades of clear cell renal cell carcinomas (P<0.0001 and <0.0245, respectively). Cytokeratin 7 was rarely seen in clear cell renal cell carcinomas, type 2 papillary renal cell carcinomas, and oncocytomas, but was found in the majority of type 1 papillary renal cell carcinomas (97.1%) and chromophobe renal cell carcinomas (88%). Aquaporin-1 and PAX-2 expression was found to correlate with nuclear grading for clear cell renal cell carcinomas but not for papillary renal cell carcinomas. No correlation of tumor stage and aquaporin-1 and PAX-2 expression was seen. Aquaporin-1 and PAX-2 are reliable markers for clear cell renal cell carcinomas of lower grades but not for higher grades. CD10 expression remains stable, independent of nuclear grading.

Dielectric properties of human brain tissue measured less than 10 h postmortem at frequencies from 800 to 2450 MHz.

The dielectric properties of gray matter in the frequency range of 800-2450 MHz were measured on 20 human brains immediately after excision, less than 10 h after death. The brains were obtained during autopsy of 10 male and 10 female humans who died at ages between 47.5 and 87.5 years [70.4 +/- 9.8 years, mean +/- standard deviation (SD)]. The tissue temperature at the measurement sites ranged between 18 and 25 degrees C (21.35 +/- 1.6 degrees C, mean +/- SD). On each brain, four specific locations on the temporal lobe were measured on the right and left sides, i.e., 160 different measurements of the dielectric properties were performed. The dielectric probe was placed on the intact arachnoid on a gyrus in the selected area. The measurements yielded a mean value (+/-SD) of gray matter equivalent conductivity of 1.13 +/- 0.12 and 2.09 +/- 0.16 S/m at 800 and 2450 MHz, respectively. The mean value of measured relative permittivity was 58.2 +/- 3.3 and 54.7 +/- 3.3 at 800 and 2450 MHz, respectively. Taking into account a positive temperature coefficient of equivalent conductivity, these measurements indicate that the equivalent conductivity of human gray matter at body temperature is somewhat higher than today's generally accepted value, which is based on measurements on animal tissue and excised samples of human tissue measured more than 24 h postmortem.

Derivation of nephrogenic adenomas from renal tubular cells in kidney-transplant recipients.

BACKGROUND: Nephrogenic adenomas are benign, tumor-like lesions within the urothelial mucosa of the urinary tract that are not uncommon in renal-transplant recipients. We investigated the origin of nephrogenic adenomas in renal-transplant recipients. METHODS: Tissue sections were analyzed by fluorescence in situ hybridization with the use of probes for the X and Y chromosomes, by immunohistochemical methods with the use of antibodies to renal tubular antigens, and by lectin histochemical methods. Forty-six nephrogenic adenomas from 29 patients were analyzed. RESULTS: All nephrogenic adenomas in 14 female recipients of transplants from male donors and 10 male recipients of transplants from female donors showed the same sex-chromosome status as the donor kidney, but not the same sex-chromosome status as the recipient's surrounding bladder tissue. The nephrogenic adenomas from all 6 female recipients of transplants from female donors showed female chromosomes, and those from the 16 male recipients of transplants from male donors showed male chromosomes. The presence of aquaporin 1, PAX2, and lectin-binding capacity for peanut agglutinin, Lotus tetragonolobus agglutinin, and Sophora japonica agglutinin in nephrogenic adenomas indicated an origin from renal tubular cells. CONCLUSIONS: Nephrogenic adenomas in renal-transplant recipients are derived from tubular cells of the renal transplants and are not metaplastic proliferations of the recipient's bladder urothelium.