Biomedical subjects

R Moll

Publications and source records attributed to R Moll.

At least 91 records · Page 5Linked to original sources

PubMed1996

Cytokeratin and vimentin expression in primary and recurrent carcinoma of the vulva: correlations with prognostic factors and the course of disease.

Radical vulvectomy for the treatment of a vulvar carcinoma inevitably entails severe psychosexual consequences for the patients. Thus, for such tumors, reliable histological prognostic parameters are needed to allow; when appropriate, the use of less radical operative measures. One possible approach to this problem might be to examine tumors immunohistochemically for the presence of cytoskeletal components. To assess the utility of this method, we applied a panel of antibodies directed against cytokeratins (CKs) and vimentin to a groups of vulvar carcinomas (62 primary and 35 recurrent tumors) and examined the results for possible correlations with the course of disease and various clinical parameters. all of the investigated CKs typical of squamous epithelia had no prognostic relevance. In contrast, the present of CKs typical of glandular differentiation as well as vimentin, suggesting early dedifferentiation, resulted in a less favorable prognosis. Thus, the procedures applied in the present study may have a role to play a decisions concerning the appropriate therapy for such tumors.

Female↗

PubMed1996

Merkel cells in mouse skin: intermediate filament pattern, localization, and hair cycle-dependent density.

The distribution and antigen expression of Merkel cells in mouse skin is as yet ill defined. Since the mouse offers an excellent model for studying the origin and functions of Merkel cells, the Merkel cell distribution as well as the expression of intermediate filament proteins and neuronal markers was characterized in C57 BL/6 mouse skin by immunohistochemistry and electron microscopy. Merkel cells in whisker pads, back, and foot pad skin as identified by staining for neuron-specific enolase-an established neuroendocrine marker--expressed cytokeratins (CK) 8,18, and 20 (i.e., simple-epithelial CKs), but not CKs 4 and 13. Sequential double staining for neuron-specific enolase and CK 20 showed consistent co-expression in Merkel cells, establishing CK 20 as a specific immunocytochemical marker for mouse Merkel cells. The Merkel cells also were immunoreactive for synaptophysin but not for neurofilament proteins, peripherin, S-100 protein, and neural cell adhesion molecule. Using CK 8, 18, and 20 as markers, we detected many Merkel cells in the outer roots sheath of vibrissae hair follicles and in foot pad skin. However, only few Merkel cells were found in back skin. These were restricted to small clusters, localized basally within the Haarscheiben epidermis of tylotrich hair follicles, and formed close contacts to prominent nerve fiber terminals as shown by electron microscopy. In striking contrast to human skin, Merkel cells were never found in the epithelium of pelage hair follicles. Even more strikingly, the density of Haarscheiben-associated Merkel cells changed substantially during the highly synchronized, depilation-induced C 57 BL/6 hair cycle, with a minimum in back skin with all hair follicles in telogen or catagen, and a maximum in back skin with all hair follicles in anagen IV-VI. These observations on the Merkel cell hair cycle-dependent distribution in murine skin point to important differences in Merkel cell functions between humans and mice, and raise intriguing questions as to the role of Merkel cells in hair biology.

Animals↗

PubMed1996

Differences of bcl-2 protein expression between Merkel cells and Merkel cell carcinomas.

The bcl-2 gene, originally identified in B-cell lymphomas, encodes for proteins which may assume oncogenic functions by blocking apoptosis. Bcl-2 proteins are broadly distributed among various tissues, including epithelial ones. Within the skin, bcl-2 is strongly expressed in melanocytes, but its further distribution is yet unclear. The Merkel cells, neuroendocrine-epithelial cells of the skin, are present within the epidermis and hair follicles, mostly nerve-associated, and are believed to be postmitotic and long lived. Possibly they give rise to the malignant Merkel cell carcinomas. In the present study we investigated the bcl-2 expression on the protein level by means of immunohistochemical techniques including double confocal laser scanning microscopy, as well as on the RNA level by RT-PCR techniques, in Merkel cells, Merkel cell carcinomas, and cell lines. Merkel cells were identified by double staining for cytokeratins 20 or 8/18. We demonstrate that fetal epidermal and dermal Merkel cells are immunostained for bcl-2 protein, most of them clearly weaker than melanocytes. Adult Merkel cells also express bcl-2 protein very heterogeneously, mostly weak. In contrast, Merkel cell carcinomas are usually strongly positive for bcl-2 protein with some degree of heterogeneity. This is different from malignant melanomas in which bcl-2 expression is reduced as compared to normal melanocytes. Bcl-2 gene expression was also shown for Merkel cell carcinoma cell lines on both the mRNA and the protein level. Possibly bcl-2 protein expression is downregulated during the life span of Merkel cells, arguing that they may succumb to a certain cell turnover. The comparably high bcl-2 protein level in Merkel cell carcinomas may reflect peculiar biological and clinical characteristics.

Adult↗

PubMed1996

Epithelioid leiomyoma of the prostate.

We report a case of an unusual mesenchymal tumor of the prostate. Rectal-digital palpation and transrectal ultrasound showed a circumscribed and inhomogeneous tumor within the right prostatic lobe. Surgical treatment consisted of transurethral resection of the right prostatic lobe. On the basis of morphology and immunohistochemical detection of desmin and smooth-muscle-type actin, the diagnosis of an epithelioid leiomyoma was made. This is the first report of this entity in the prostate. A definite prediction of the biological potential is currently not yet possible.

Humans↗

PubMed1996

[Cell adhesion molecules and extracellular matrix components as target structures of autoimmunity].

A number of cell-cell and cell-matrix adhesion molecules as well as several extracellular matrix components represent target structures of antibody-mediated autoimmunity which recently have been extensively characterized at the molecular biological level. Pathogenic autoantibodies against these molecules have been found to be causally related to disturbances of cell and tissue adhesion that become apparent as various (muco-)cutaneous blistering diseases. In desmosomes, desmosomal cadherins (desmogleins and desmocollins) mediate epidermal intercellular adhesion. Among these, desmoglein 1 and desmoglein 3 are the autoantigens of pemphigus foliaceus and pemphigus vulgaris, respectively, being characterized by intraepidermal blistering. The pathogenic relevance of autoantibodies against desmocollins (IgA pemphigus and other pemphigus types) and desmoplakins (paraneoplastic pemphigus) still remains unclear. Hemidesmosomes contain the plaque protein BPAG1 and the partly collagen-like transmembrane protein BPAG2, representing the autoantigens of bullous pemphigoid and pemphigoid gestations which show subepidermal blistering. A certain subtype of cicatricial (benign mucous membrane) pemphigoid is characterized by autoantibodies against laminin 5 present in the subhemidesmosomal anchoring filaments. Both epidermolysis bullosa acquisita and bullous SLE exhibit autoantibodies against collagen type VII which constitutes the anchoring fibrils. Besides, autoantibodies against a particular collagen type IV chain of the glomerular basement membrane are responsible for the manifestation of Goodpasture's syndrome. These recent molecular biological findings might be the basis for the development of novel therapeutic strategies.

Animals↗

PubMed1995

EPR characterization of an archaeal succinate dehydrogenase in the membrane-bound state.

The membrane-bound succinate dehydrogenase from the thermoacidophilic archaeon Thermoplasma acidophilum was characterized by EPR spectroscopy and its functional properties were determined. The highest turnover values of succinate dehydrogenase activity were observed at pH 7.4, which is somewhat above the internal pH value of T. acidophilum. The temperature optimum of the reaction was determined as 78 degrees C and the Km value for succinate using phenazine methosulfate as the electron acceptor at 53 degrees C was 0.32 mM. The membrane-bound enzyme was able to reduce the artificial electron acceptors phenazine methosulfate, N,N,N',N'-tetramethyl-p-phenylenediamine, and 2,6-dichloroindophenol. Succinate oxidation was coupled to oxygen consumption in a completely 2-n-heptyl-4-hydroxyquinoline-N-oxide-sensitive manner. In the oxidized state, T. acidophilum membranes exhibited an almost isotropic EPR spectrum with g-values at gz = 2.017, gy = 2.000, and gx = 1.968 that were assigned to a [3Fe-4S]1+ cluster (S3). Upon reduction with succinate, the membranes displayed a spectrum characteristic of 2Fe-2S clusters (S1), with g-values at gz = 2.029, gy = 1.935, and gx = 1.915. In the dithionite-reduced state, additional resonances can be observed. An axial component, with g-values at gz = 2.057, gy = 1.917, and gx = 1.917 was assigned to a [4Fe-4S]1+ cluster. The saturation behaviour of the S1 cluster was strongly altered in the dithionite-reduced form, thus indicating spin-spin interaction between the S1 center and another paramagnetic center, possibly cluster S2. In both the succinate and the dithionite-reduced membranes, parallel-mode EPR spectra displayed a resonance at g = 14, which may be due to a transition of the S = 2 multiplet of the reduced 3Fe-4S cluster. Spin quantitation yielded a relative stoichiometry of cluster S1 to cluster S3 of 1:1. The results obtained by EPR spectroscopy indicated that the characteristic iron-sulfur cluster S1 [2Fe-2S], S2 [4Fe-4S], and S3 [3Fe-4S], were also present in this archaeal succinate dehydrogenase. EPR redox titrations of T. acidophilum membranes at pH 5.5 yielded a reduction potential of +60 +/- 20 mV for cluster S3 and of +68 +/- 20 mV for cluster S1. The axial [4Fe-4S]2+/1+ center had a reduction potential of -210 +/- 20 mV.

Dithionite↗

PubMed1995

Purification, cloning, and sequencing of archaebacterial pyrophosphatase from the extreme thermoacidophile Sulfolobus acidocaldarius.

Cytoplasmic pyrophosphatases are indispensible for the function of cellular bioenergetics. From the extreme thermoacidophilic archaeon Sulfolobus acidocaldarius, situated at one of the lowest branches of the phylogenetic tree, a cytosolic pyrophosphatase has been isolated and purified 200-fold to electrophoretic homogeneity by combining ion-exchange and gel-exclusion chromatography. The native enzyme consists of a homotetramer of 71 kDa apparent molecular mass; the subunit displays an apparent molecular mass of 17 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme has an absolute requirement for divalent cations (Mg2+) and a temperature optimum of 75 degrees C coinciding with the growth optimum of the organism; the apparent estimated activation energy is 79.5 kJ/mol. A large variety of cytosolic extracts from other archaebacteria has been probed with a polyclonal antiserum raised against the purified protein; surprisingly, except for an extremely weak signal with S. solfataricus none of the other organisms showed any cross-reactivity. Also, Escherichia coli PPase does not cross-react. Based on N-terminal sequencing the gene has been cloned and sequenced. It codes for a 173-amino-acid protein with a calculated molecular mass of 19,365 kDa. Alignment with known eucaryotic and procaryotic PPases reveals invariant conservation of all residues presently assumed to be involved in metal and substrate binding. Unexpectedly, the highest similarity is found with the enzyme from the phylogenetically extremely distant eubacterium E. coli, but immunological cross-reactivity is absent. Similarity to the only known other archaebacterial PPase is much weaker. Using the 3D structure of the Thermus thermophilus enzyme as a scaffold an energy-minimized structural model is presented, deviating only minimally from the former. The structural features are discussed. The enzyme provides an excellent model for studies of thermostability and folding dynamics since heterologous overexpression has been achieved and genetically mutated forms become accessible.

Amino Acid Sequence↗

PubMed1995

Nucleotide sequence of a gene cluster encoding ribosomal proteins in the thermoacidophilic crenarchaeon Sulfolobus acidocaldarius.

A 1.6 kb genomic DNA fragment derived from the extremely thermoacidophilic archaeon Sulfolobus acidocaldarius (DSM 639) comprises four open reading frames. The sequence contains three genes encoding crenarchaeal ribosomal proteins with apparent molecular masses of 6.3 kDa, 15.2 kDa and 9.9 kDa, which all represent strongly basic properties. These were identified by sequence comparison as RL46, RL31 and RL33. One open reading frame encodes a new polypeptide (22.1 kDa, pI = 7.3) with no homology to known proteins. The latter is transcribed as a common mRNA with RL46 and RL31. This gene cluster immediately precedes another cluster including genes encoding the putative SRP receptor alpha subunit as well as the putative secEp.

Amino Acid Sequence↗

PubMed1995

New cell lines of gastric and pancreatic cancer: distinct morphology, growth characteristics, expression of epithelial and immunoregulatory antigens.

Two new cell lines from stomach cancers and one from a pancreatic carcinoma are presented. MZ-GC-1 was established from a hepatic metastasis of a well differentiated gastric adenocarcinoma. MZ-GC-2 was derived from ascites induced by a poorly differentiated gastric adenocarcinoma. MZ-PC-1 originated from the pleural effusion of a moderately well differentiated pancreatic ductal adenocarcinoma. MZ-GC-1 cells were adherent and partially polarized, connected tightly via desmosomes. In contrast MZ-GC-2 cells consisted of slightly adherent or floating subpopulations and displayed no desmosomes. MZ-PC-1 cells were adherent and showed polarized growth, connected by apical junctional complexes. Cell doubling times were 7 days for MZ-GC-1 and 45 h for MZ-GC-2 and MZ-PC-1 cells. MZ-GC-2 and MZ-PC-1 gave rise to nude mouse tumours, resembling the original lesions. Chromosome analysis of the cell lines revealed a high range of numerical abnormalities. Each cell line had cytokeratin patterns fitting well to typical in vivo patterns. Furthermore the cell lines expressed a panel of antigens typical for gastrointestinal epithelia. Unique for MZ-PC-1 were high amounts of secreted Ca19-9. gamma-Interferon enhanced HLA-class I antigens up to twofold and induced ICAM-1 expression on each cell line. HLA-class II antigens were differentially enhanced by gamma-interferon. Due to their distinct characteristics the three tumour cell lines may be useful models in the investigation of the cell biology and immunogenicity of gastrointestinal tumours.

Adenocarcinoma↗

PubMed1995

Increased numbers of cytokeratin-positive interstitial reticulum cells (CIRC) in reactive, inflammatory and neoplastic lymphadenopathies: hyperplasia or induced expression?

A total of 291 enlarged lymph nodes showing a range of reactive-inflammatory processes, primary and metastatic neoplasms were studied to determine the distribution and immunoprofile of their cytokeratin-positive interstitial reticulum cells (CIRC) in comparison with normal nodes. In 258/291 nodes (89%), CIRC numbers were distinctly increased in the subcapsular, paracortical and, occasionally, in the medullary zones; often, these increased CIRC formed networks around follicles, sinuses and vessels. CIRC had comparatively small, irregularly shaped bodies and dendritic processes; occasionally, giant forms were noted. CIRC contained cytokeratins (CK) 8 and 18 but not 19, as shown by immunohistochemistry, and by gel electrophoresis with subsequent immunoblotting. They co-expressed vimentin consistently, alpha-smooth-muscle actin frequently, and desmin less frequently. They did not contain desmoplakins, Factor VIII, S-100, LCA, B and T lymphocyte- and macrophage-associated antigens, chromogranin A, synaptophysin or the A-80 glycoprotein. We found no clear correlation between the increased CIRC and given nodal disease processes. However, CIRC were most abundant in nodes free of but draining malignant tumours; bizarre CIRC assemblies were noted in HIV lymphadenopathy. CIRC appear to represent a subset of the so-called "fibroblastic reticulum cells" of lymph nodes. Their function remains undetermined; their increase in diverse lymphadenopathies suggests that they partake in nodal reactions to injury. It remains unclear whether the increase in CIRC relative number is due to proliferation or to CK gene induction processes but their presence and potential capability to undergo hyperplasia with dysplastic forms should alert pathologists to possible diagnostic pitfalls. In addition, we discuss that CIRC may undergo transformation and represent the "cell of origin" of certain CK-positive tumours restricted to lymph nodes.

Cytoskeletal Proteins↗

PubMed1995

Differentiation potential of ovarian dysgerminoma: an immunohistochemical study of 15 cases.

An immunohistochemical study of 15 ovarian formalin-fixed, paraffin-embedded dysgerminomas showed positive staining of tumor cells for vimentin in all cases. Ten dysgerminomas stained for cytokeratin 18. Desmin positivity of single tumor cells was detected in four dysgerminomas. Glial fibrillary acidic protein was present in two tumors. Prominent human beta chorionic gonadotropin staining was seen in one tumor. S-100 protein was found in two and carcinoembryonic antigen in one of the dysgerminomas. Placental alkaline phosphatase was present in 12 of the 15 tumors studied. The heterogeneity of the cytoskeletal profile and of other markers showed some similarities to our previously published results on testicular seminomas. Thus, in contrast to previous concepts, dysgerminoma, as is the case with its testicular counterpart the seminoma, appears to be capable of further differentiation, albeit at a primitive level. Our observations also may help to elucidate the relationship between dysgerminoma and other nondysgerminomatous ovarian germ cell tumors, and may be of help in the differential diagnosis with poorly differentiated carcinoma, ovarian lymphoma, or other germ cell tumors.

Biomarkers, Tumor↗

PubMed1995

Gynaecomastia in a patient with a hCG producing giant cell carcinoma of the lung. Case report.

Gynaecomastia, or enlargement of the male breast may result from various endocrine dysfunctions and often reflects ectopic production of substances such as hCG and estradiol. We report on the case of a 30 year old man who presented with gynaecomastia and elevated plasma levels of hCG, estradiol and testosterone. As a result of several diagnostic procedures such as selective venous sampling and magnetic resonance tomography (MRT), a hCG producing tumor of the upper lobe of the left lung was found. This hormonal overproduction induced an enhanced secretion of estradiol and testosterone in the testicular tissue. Histology revealed a giant cell carcinoma with positive immunostaining for hCG. This case report further underlines the necessity of an intensive search for ectopic beta-hCG production due to malignant tumours, in particular in the adult.

Adult↗

PubMed1995

Cytokeratin 20 is a general marker of cutaneous Merkel cells while certain neuronal proteins are absent.

Merkel cells are difficult to identify in tissue sections. Previous studies have used cytokeratins (CK) 8, 18, and 19 as histologic markers of Merkel cells. However, these CKs are also expressed in some outer root sheath keratinocytes and some early fetal epidermal cells and thus are not truly specific of Merkel cells in general. Using selective antibodies against a newly described CK, number 20--originally found in intestinal epithelium and Merkel cell carcinomas--in comparison to a key protein of neuroendocrine cells, chromogranin A, we established CK 20 as a specific Merkel cell marker in skin of humans, pigs, and mice. CK 20 seems to be an even more general and sensitive Merkel cell marker as compared to CgA. In double-labeling experiments with stratified-squamous epithelial CK (numbers 5 and 13-17) and simple epithelial CK (numbers 8, 18, and 20) antibodies evaluated by confocal laser scanning microscopy, no cell expressing CKs of both types (i.e., no cell of so-called "transitional" character between Merkel cells and keratinocytes) was identified in human skin. In addition, various neuronal markers present in Merkel cell carcinomas including neurofilaments, peripherin, nerve growth factor receptor, and neuronal cell adhesion molecule appear to be absent in normal Merkel cells. Thus, Merkel cells exhibit a distinct and unique marker profile, with CK 20 being of particularly high value in various species.

Adult↗

PubMed1995

Epithelial markers and differentiation in adnexal neoplasms of the skin: an immunohistochemical study including individual cytokeratins.

Applying immunohistochemical procedures for the detection of eight different cytokeratin (CK) polypeptides and other differentiation markers, we compared the staining patterns of normal cutaneous structures with those of benign adnexal tumors (n = 65). Syringomas exhibited a marker pattern highly reminiscent of that seen in normal dermal eccrine ducts (EMA in peripheral cells, CK 10 in intermediate cells, and CK 6, CK 19, and CEA in luminal cells). Nodular hidradenomas exhibited complex patterns suggesting relationship between tumor cells, including clear cells, and normal secretory coil cells (CK 7, CK 8, CK 19, and EMA); however, dermal-duct and epidermoid differentiation were also detectable. In both cylindromas and spiradenomas, zonal staining patterns were apparent: modified myoepithelial cells were positive for smooth-muscle-type actin, while the luminal cells mainly expressed ductal markers (CK 6 and CK 19) and, less prominently, secretory-coil markers including CK 7. Eccrine poromas exhibited a widespread reaction for CK 5/6 and EMA, analogous to peripheral dermal duct cells, but focal maturation toward inner-ductal and secretory-coil cells was also demonstrable. The staining pattern observed in trichoepitheliomas resembled that of the outer but not the inner root sheath. In conclusion, the detailed marker profiles obtained in the present study have broadened our understanding of the differentiation and nature of these highly singular tumor types.

Adenoma↗

PubMed1995

[Recent prognostic factors in vulvar carcinoma: histological, immunohistochemical and flow cytometry studies].

OBJECTIVES: Are newer histologic investigations helpful in the evaluation of the prognosis of vulvar carcinoma? METHODS: 147 primary squamous cell carcinomas of the vulva were examined for overall- and disease-free survival (mean observation 59.6 months). RESULTS: A significance in prognosis was found for FIGO-stage, a new-created histologic grade, p53- and vimentin-expression and amount of T-lymphocytes in tumoral stroma. Unfavourable prognosis was detected for tumors with elevated growth fraction, high proliferating cell-compartment (S + G2 + M) and increased cytokeratin-8-expression. CONCLUSIONS: These investigations are able to describe the malignant potential of a vulvar carcinoma and should therefore influence the decision for a modified radical therapy.

Biomarkers, Tumor↗

PubMed1995

Uroplakins, specific membrane proteins of urothelial umbrella cells, as histological markers of metastatic transitional cell carcinomas.

Uroplakins (UPs) Ia, Ib, II, and III, transmembrane proteins constituting the asymmetrical unit membrane of urothelial umbrella cells, are the first specific urothelial differentiation markers described. We investigated the presence and localization patterns of UPs in various human carcinomas by applying immunohistochemistry (avidin-biotin-peroxidase complex method), using rabbit antibodies against UPs II and III, to paraffin sections. Positive reactions for UP III (sometimes very focal) were noted in 14 of the 16 papillary noninvasive transitional cell carcinomas (TCCs) (88%), 29 of the 55 invasive TCCs (53%), and 23 of the 35 TCC metastases (66%). Different localization patterns of UPs could be distinguished, including superficial membrane staining like that found in normal umbrella cells (in papillary carcinoma), luminal (microluminal) membrane staining (in papillary and invasive carcinoma), and, against expectations, peripheral membrane staining (in invasive carcinoma). Non-TCC carcinomas of various origins (n = 177) were consistently negative for UPs. The presence of UPs in metastatic TCCs represents a prime example of even advanced tumor progression being compatible with the (focal) expression of highly specialized differentiation repertoires. Although of only medium-grade sensitivity, UPs do seem to be highly specific urothelial lineage markers, thus operating up interesting histodiagnostic possibilities in cases of carcinoma metastases of uncertain origin.

Amino Acid Sequence↗

PubMed1995

Development of renal podocytes cultured under medium perifusion.

BACKGROUND: In the past, podocytes have been described as highly susceptible to dedifferentiation under cell culture. Whether this process resulted from insufficient culture conditions or whether it was a consequence of missing cellular interactions remained unclear. A further reason could be that podocytes within the maturing kidney are irreversibly growth-arrested at a very early point of development because proliferating cells have been detected at the S-shaped body stage but not at the capillary loop stage or in the maturing glomeruli. These were important reasons that hindered the establishment of podocyte cell culture systems. EXPERIMENTAL DESIGN: The aim of our present study was to culture podocytes under the most organotypic conditions possible to maintain typical cellular characteristics. Cortex explants of neonatal rabbit kidneys consisting of nephrogenic tissue were used as a source for podocytes. No serum additives were given for the whole culture period of 13 days. An organ-specific environment was obtained by keeping the podocytes within the surrounding renal tissue and by ensuring a permanent exchange of medium. RESULTS: mAb were used to characterize podocytes and the other glomerular cell types. Cultured podocytes and parietal cells of Bowman's capsule were identified by EnPo 1. Ks 19.2.105, a marker for cytokeratin 19, was used to discriminate among these epithelial cells because cytokeratin 19 is expressed by the parietal cells of Bowman's capsule but not by podocytes. The Ab EC1 specifically detected endothelial cells. Glomerular endothelium cultured under medium perifusion expressed these typical Ag and thus could be unequivocally discriminated. Furthermore, by means of the proliferation marker Ki-67, it could be demonstrated that glomerulus-like structures developed under culture by proliferation of visceral and parietal cells of Bowman's capsule. CONCLUSIONS: A culture model is presented that allows the maintenance of developing podocytes within the organ-specific tissue environment and under permanent medium perifusion.

Animals↗

PubMed1995

Establishment and characterization of two divergent cell lines derived from a human chromophobe renal cell carcinoma.

The chromophobe renal cell carcinoma is a distinct type of renal cancer presumably derived from the intercalated cell of the collecting duct system and exhibiting a better prognosis than other types of renal cell carcinoma. Chromophobe carcinomas can be separated from other types of renal cell carcinoma by their characteristic cytomorphology, ultrastructural appearance, cytoskeletal architecture, and cytogenetic aberrations. As no permanent cell line of the chromophobe tumor type has previously been described, we are the first to report on the successful establishment and characterization of two divergent permanent cell lines, ie, chrompho-A and chrompho-B, derived from the same chromophobe renal cell carcinoma. With immunocytochemistry, two-dimensional gel electrophoresis, and Western blot, chrompho-A and chrompho-B exclusively exhibited cytokeratins (Nos. 7, 8, 18, and 19) but not vimentin. Ultrastructural studies revealed numerous cytoplasmic microvesicles as well as coated vesicles that are known to be characteristic features of the intercalated cell. Chrompho-B cells exhibited a shorter mean population doubling time (tD = 43 hours) than chrompho-A cells (tD = 51 hours). Both cell lines failed to produce tumors in nude mice with the subrenal capsule assay. Cytogenetic analyses revealed hyperdiploid chromosome numbers in both cell lines with telomeric associations as well as numeric aberrations known from chromophobe renal cell carcinomas in vivo.

Aged↗