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Biomedical subjects

K Fujikawa

Publications and source records attributed to K Fujikawa.

At least 109 records · Page 6Linked to original sources
PubMed1999

A case of malignant lymphoma producing autoantibody against platelet glycoprotein Ib.

A 61-year-old woman was referred to our hospital for refractory thrombocytopenia (3 x 10(3)/microliter) and massive melena. Bone marrow aspiration revealed normal cellularity and increased megakaryocytes (250/microliter). An abdominal computerized axial tomography scan showed isodensity masses on both adrenal glands. 67 Ga-scintigraphy exhibited strong uptake into the bilateral adrenal tumor and mediastinal region. IgM-type antibody against platelet glycoprotein Ib (GpIb) was detected in the patient's serum. A needle biopsy of the right adrenal tumor was performed, and histology was non-Hodgkin's lymphoma (NHL), diffuse large B-cell type. Following the diagnosis of autoimmune thrombocytopenia associated with lymphoma, administration of corticosteroid (predonisolone 60 mg/day) and high-dose intravenous globulin (15 g/day x 4 days) was carried out, but neither was effective in normalizing the thrombocytopenia. Immunosuppressive therapy (cyclophosphamide 500 mg and 1 mg of vincristine) markedly restored the platelet counts to 7.2 x 10(4)/microliter and ceased the melena; furthermore, the size of adrenal tumors decreased by more than 60% after therapy. We cultured the lymphoma cells drawn by needle biopsy with IL-6 in vitro and found that the lymphoma cells produced IgM-type antiplatelet antibodies against platelet GpIb in the culture supernatant. Thus this is a rare case of NHL in which the production of antiplatelet antibody from lymphoma cells was confirmed in vitro.

Autoantibodies↗
PubMed1998

Malignant tumors of the kidney, brain, and soft tissues in children and young adults with the tuberous sclerosis complex.

BACKGROUND: The tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by seizures, mental retardation, and benign tumors of the brain, heart, skin, and kidney. Malignant tumors also can occur in patients with tuberous sclerosis, particularly in the kidney, although they occur less frequently than benign tumors. The types of malignancy that occur in TSC have not been characterized fully. METHODS: Clinical and pathologic features of 8 malignant tumors from 6 TSC patients ranging in age from 22 months to 21 years are reviewed. Six tumors were renal, one was from the inguinal region, and one was from the brain. The tumors were analyzed for loss of heterozygosity (LOH) in the chromosomal regions of the TSC1, TSC2, and VHL genes. RESULTS: Three patients (ages 7, 8, and 20 years) had renal cell carcinomas (RCCs). Two of these patients had multifocal RCCs. All three patients with RCC also had prominent multifocal dysplasia of renal cyst epithelium. Two patients (ages 20 and 21 years) had malignant angiomyolipomas (1 renal and 1 inguinal). One patient (age 22 months) had a Grade 4 giant cell astrocytoma (glioblastoma multiforme). LOH in the region of the TSC2 gene was found, either in the malignant tumor or in benign tumors, in all five patients whose DNA could be analyzed. CONCLUSIONS: Children with TSC, as well as adults with the disease, are at risk for developing malignant tumors. Two types of renal malignancy occur in TSC: RCC, which appears to arise from dysplastic renal cyst epithelial cells, and malignant angiomyolipoma. Tumors cytologically similar to malignant angiomyolipomas also may occur at extrarenal sites. LOH analyses suggest that the majority of patients with TSC who develop malignant tumors have germline TSC2, rather than TSC1, gene mutations.

Adult↗
PubMed1998

The mutations induced by oxidatively damaged nucleotides, 5-formyl-dUTP and 5-hydroxy-dCTP,in Escherichia coli.

The mutational properties of 5-formyl-2'-deoxyuridine 5'-triphosphate (5-CHO-dUTP) and 5-hydroxy-2'-deoxycytidine 5'-triphosphate (5-OH-dCTP), the major oxidatively damaged pyrimidine nucleotides derived from dTTP and dCTP, respectively, were analyzed by an in vivo assay. 5-CHO-dUTP and 5-OH-dCTP were directly incorporated into Escherichia coli , and their mutagenicities were evaluated by the chromosomal lacI forward mutation assay. The mutation frequencies increased, depending on the dose of these damaged nucleotides, indicating that these nucleotides were incorporated into E.coli and acted as mutagens in vivo . The mutagenicities of 5-CHO-dUTP and 5-OH-dCTP were comparable to that of 8-hydroxy-2'-deoxyguanosine 5'-triphosphate, a major form of dGTP oxidative damage. 5-CHO-dUTP induced G.C to A.T, A.T to G.C and G.C to T.A mutations, and 5-OH-dCTP elicited G.C to A.T, A.T to C.G and G.C to T.A mutations.

Bacterial Proteins↗
PubMed1998

Combining volume-weighted mean nuclear volume with Gleason score and clinical stage to predict more reliably disease outcome of patients with prostate cancer.

BACKGROUND: Various criteria for patients with prostate cancer have been reported to be of prognostic value, and we have reported that estimates of volume-weighted mean nuclear volume (MNV), developed by Gundersen and Jensen based on a stereological technique, accurately predict the prognosis of prostate cancer. However, all of these studies were conducted on cases in a single institution, and it has remained unclear whether MNV calculations obtained at one institution apply to cases at another institution. In attempting to solve this problem, we made a prognostic index (P.I.) based on data from one hospital, and tested whether these data could be used to predict the prognosis of patients at another hospital. MATERIALS AND METHODS: A retrospective, multivariate prognostic study of 195 patients with prostate cancer, diagnosed at Kyoto University Hospital and treated conservatively, indicated that clinical stage, Gleason score, and MNV were all significantly correlated with the prognosis of patients with prostate cancer. From the relative strengths of these prognostic factors in a multivariate analysis, the following P.I. was constructed: P.I. = Clinical stage x 1.8040 + Gleason score x 1.5245 + MNV x 2.3162 (the constants correspond to the risk ratio estimated by Cox analysis). The P.I. was calculated for 104 patients with prostate cancer diagnosed at Shizuoka City Hospital and treated conservatively for analysis of disease-specific survival. RESULTS: The prognostic index ranged from 3.841-16.142. Using the median value of 12.5 as a cutoff point, a clear separation of cases with poor and favorable prognosis was achieved (P < 0.0001, observation period: 1-167 months). CONCLUSIONS: The results of this study suggest that estimates of MNV can be evaluated at multiple institutions with the use of P.I. calculation. Furthermore, combining estimates of MNV with Gleason score and clinical stage predicts most powerfully disease outcome of patients with prostate cancer.

Aged↗
PubMed1998

Tie2 receptor ligands, angiopoietin-1 and angiopoietin-2, modulate VEGF-induced postnatal neovascularization.

Angiopoietin-1 (Ang1) has been recently identified as the major physiological ligand for the tyrosine kinase receptor Tie2 and assigned responsibility for recruiting and sustaining periendothelial support cells. Angiopoietin-2 (Ang2) was found to disrupt blood vessel formation in the developing embryo by antagonizing the effects of Ang1 and Tie2 and was thus considered to represent a natural Ang1/Tie2 inhibitor. In vivo effects of either angiopoietin on postnatal neovascularization, however, have not been previously described. Accordingly, we used the cornea micropocket assay of neovascularization to investigate the impact of angiopoietins on neovascularization in vivo. Neither Ang1 nor Ang2 alone promoted neovascularization. Pellets containing vascular endothelial growth factor (VEGF) alone induced corneal neovascularity extending from the limbus across the cornea. Addition of Ang 1 to VEGF (Ang1+VEGF) produced an increase in macroscopically evident perfusion of the corneal neovasculature without affecting macroscopic measurements of length (0.58+/-0.03 mm) or circumferential neovascularity (136+/-10 degrees). In contrast, pellets containing Ang2+VEGF promoted significantly longer (0.67+/-0.05 mm) and more circumferential (160+/-15degrees) neovascularity than VEGF alone or Ang1+VEGF (P<0.05). Excess soluble Tie2 receptor (sTie2-Fc) precluded modulation of VEGF-induced neovascularization by both Ang2 and Ang1. Fluorescent microscopic findings demonstrated enhanced capillary density (fluorescence intensity, 2.55+/-0.23 e+9 versus 1.23+/-0.17 e+9, P<0.01) and increased luminal diameter of the basal limbus artery (39.0+/-2.8 versus 27.9+/-1.3 microm, P<0.01) for Ang1+VEGF compared with VEGF alone. In contrast to Ang1+VEGF, Ang2+VEGF produced longer vessels and, at the tip of the developing capillaries, frequent isolated sprouting cells. In the case of Ang2+VEGF, however, luminal diameter of the basal limbus artery was not increased (26.7+/-1.9 versus 27.9+/-1.3, P=NS). These findings constitute what is to our knowledge the first direct demonstration of postnatal bioactivity associated with either angiopoietin. In particular, these results indicate that angiopoietins may potentiate the effects of other angiogenic cytokines. Moreover, these findings provide in vivo evidence that Ang1 promotes vascular network maturation, whereas Ang2 works to initiate neovascularization.

Angiopoietin-1↗
PubMed1998

The Ets-1 and Ets-2 transcription factors activate the promoters for invasion-associated urokinase and collagenase genes in response to epidermal growth factor.

Urokinase plasminogen activator (uPA) has been associated with invasion and metastasis in breast cancer. The expression of uPA and 92 kDa type IV collagenase (gelatinase B/MMP-9) is regulated by growth factors, receptor-type tyrosine kinases and cytoplasmic oncoproteins. Here, we have identified transcriptional requirements for the induction of uPA and 92 kDa type IV collagenase by epidermal growth factor (EGF). EGF stimulates the motile and invasive activities specifically in the ErbB-2-overexpressing SK-BR-3 cells. Expression of extracellular matrix-degrading proteases including type I collagenase/MMP-1, 92 kDa type IV collagenase/MMP-9, uPA and uPA receptor were induced. EGF also transiently stimulated expression of the transcription factors Ets-1 and Ets-2. Reporter transfection assays revealed the activation of uPA and MMP-9 collagenase promoters by EGF and the requirement of each of the composite Ets and AP-1 transcription factor binding sites for an EGF response. Most notably, transfections with the Ets-1 and Ets-2 expression vectors potentiated uPA and MMP-9 promoter activation in response to EGF. Mutation of the threonine 75 residue of chicken Ets-2 conserved in the Pointed group of the Ets family proteins abrogated the ability of Ets-2 to collaborate with EGF. Ets-1 and Ets-2 were highly expressed in invasive breast tumor cell lines. Our results suggest that Ets-1 and Ets-2 provide the link connecting EGF stimuli with activation of uPA and 92 kDa type IV collagenase promoters and may contribute to invasion phenotypes.

Breast Neoplasms↗
PubMed1998

Concentrations of thrombopoietin in bone marrow in normal subjects and in patients with idiopathic thrombocytopenic purpura, aplastic anemia, and essential thrombocythemia correlate with its mRNA expression of bone marrow stromal cells.

The function of bone marrow (BM) stromal thrombopoietin (TPO) in megakaryopoiesis remains unknown. In the present study we attempted to clarify the pathophysiological implications of stromal TPO in normal subjects (NS) and in patients with idiopathic thrombocytopenic purpura (ITP), aplastic anemia (AA), and essential thrombocythemia (ET) by measuring TPO concentrations in BM and peripheral blood (PB) and by estimating the levels of stromal TPO mRNA with TaqMan fluorescence-based post-reverse transcription-polymerase chain reaction product detection system. The results showed that TPO concentrations in PB were significantly elevated in patients with ITP (34.9 +/- 11.7 pg/mL) and AA (364.1 +/- 153.5 pg/mL) but within normal range in patients with ET (each 20.0 and 22.1; NS, 22.1 +/- 8.2 pg/mL). In all subjects, the TPO concentrations in BM correlated well with the PB levels, and the former were consistently higher than the latter. The concentrations of TPO in BM also correlated with the levels of TPO mRNA in stromal cells. Furthermore, expression levels of TPO mRNA clearly correlated with megakaryocyte counts in NS and patients with ITP, indicating that stromal TPO actually enhances megakaryopoiesis. Thus, our results in the present study indicate that TPO from BM stromal cells is considered to play an essential role for megakaryopoiesis under various patho-physiological conditions.

Anemia, Aplastic↗
PubMed1998

Induction of chromosomal gene mutations in Escherichia coli by direct incorporation of oxidatively damaged nucleotides. New evaluation method for mutagenesis by damaged DNA precursors in vivo.

We have developed a new strategy for the evaluation of the mutagenicity of a damaged DNA precursor (deoxyribonucleoside 5'-triphosphate) in Escherichia coli. 8-Hydroxydeoxyguanosine triphosphate (8-OH-dGTP) and 2-hydroxydeoxyadenosine triphosphate (2-OH-dATP) were chosen for this study because they appear to be formed abundantly by reactive oxygen species in cells. We introduced the oxidatively damaged nucleotides into competent E. coli and selected mutants of the chromosomal lacI gene. Both damaged nucleotides induced lacI gene mutations in a dose-dependent manner, whereas unmodified dATP and dGTP did not appear to elicit the mutations. The addition of 50 nmol of 8-OH-dGTP and 2-OH-dATP into an E. coli suspension induced 12- and 9-fold more substitution mutations than the spontaneous event, respectively. The 8-OH-dGTP induced A.T --> C.G transversions, and the 2-OH-dATP elicited G.C --> T.A transversions. These results indicate that the two oxidatively damaged nucleotides are mutagenic in vivo and suggest that 8-OH-dGTP and 2-OH-dATP were incorporated opposite A and G residues, respectively, in the E. coli DNA. This new method enables the evaluation and comparison of the mutagenic potentials of damaged DNA precursors in vivo.

Bacterial Proteins↗
PubMed1998

HRG Tokushima: molecular and cellular characterization of histidine-rich glycoprotein (HRG) deficiency.

Previously, we found the first congenital deficiency of histidine-rich glycoprotein (HRG) in a Japanese woman with thrombosis. To elucidate the genetic basis of this deficiency, we first performed Southern blot analysis and found no gross deletion or insertion in the proband's HRG gene. We then examined the nucleotide sequences of all seven exons of the proband's HRG gene. A single nucleotide substitution, G to A at nucleotide position 429, which mutates Gly85 to Glu in the first cystatin-like domain, was found in exon 3 in 13 of 22 amplified clones. This mutation generates a unique Taq I site. Exon 3 was amplified from the proband, her family members, and 50 unrelated normal Japanese individuals, and Taq I fragmentation was examined. Fragmentation of exon 3 was observed in one allele of the genes from the proband and the family members who also have decreased plasma levels of HRG. Fifty unrelated normal Japanese individuals had a normal HRG gene, indicating that the G to A mutation is not a common polymorphism. To elucidate the identified mutation as a cause for the secretion defect of HRG in the proband's plasma, we constructed and transiently expressed the recombinant Tokushima-type HRG mutant (Gly85 to Glu) in baby hamster kidney (BHK) cells, and examined an intracellular event of the mutant protein. The results showed that only about 20% of the Tokushima-type HRG was secreted into the culture medium, and intracellular degradation of the mutant was observed. Thus, the present study strongly suggests that the HRG deficiency is caused by intracellular degradation of the Gly85 to Glu mutant of HRG in the proband.

Adult↗
PubMed1998

SEK1/MKK4 is required for maintenance of a normal peripheral lymphoid compartment but not for lymphocyte development.

SAPK is a member of the group of evolutionary conserved stress-activated kinases that mediate control of cellular death and proliferation. In lymphocytes, the SAPK pathway has been implicated in signaling from antigen, costimulatory, and death receptors; SEK1, which directly activates SAPK, is required for early embryonic development and has also been reported to be essential for normal lymphocyte development. In contrast to the latter findings, we have used RAG-2-deficient blastocyst complementation to show that SEK1-deficient embryonic stem cells support unimpaired T and B lymphocyte development. Moreover, mature SEK1-deficient lymphocytes are capable of SAPK activation. Surprisingly, however, aging SEK1-deficient chimeric mice frequently develop lymphadenopathy and polyclonal B and T cell expansions. Thus, SEK1 is not required for lymphocyte development, but is required for maintaining peripheral lymphoid homeostasis.

Animals↗
PubMed1998

Spectroscopic studies on the interaction of pradimicin BMY-28864 with mannose derivatives.

Pradimicin BMY-28864 (Pm) is an antibiotic effective against yeasts and fungi, and is known to bind mannose in the presence of Ca2+. We examined spectroscopically the mode of interactions among Pm, Ca2+, and glycosides of mannose and mannose oligosaccharides (Manalpha1-OMe, Manalpha1-2Manalpha1-OMe, Manalpha1-3Manalpha1-OMe, Manalpha1-4Manalpha1-OMe, Manalpha1-6Manalpha1-OMe, Manalpha1-6(Manalpha1-3)Manalpha1-OMe, and Man9GlcNAc2-Asn, a high mannose type N-linked oligosaccharide). All the mannosides interacted with Pm in the presence of Ca2+ and caused absorbance changes. The absorbance changes occurred nonlinearly with respect to the carbohydrate concentration and do not follow a simple binding isotherm equation, suggesting a unique multistep interaction mode. The concentrations that induced half the maximum absorbance change were approximately 10 mM for the mono- and di-mannosides and around 1.5 mM for the trimannoside and Man9GlcNAc2-Asn. Methyl alpha-D-glucopyranoside, methyl alpha-D-galactopyranoside, lactose, and myo-inositol did not affect the absorbance of Pm up to 50 mM. Ca2+ alone also influenced the absorbance of Pm. The absorbance between 200 and 700 nm decreased hypochromically when Ca2+ was added. The concentration that gave half the maximum absorbance decrease caused by Ca2+was around 15 microM. Our results suggest that two Pm molecules bind one C a2+, and each Pm binds two mannosyl residues.

Anthracyclines↗
PubMed1998

Tensile load and the metabolism of anterior cruciate ligament cells.

It generally is recognized that tensile load plays a major role in maintaining the homeostasis of the anterior cruciate ligament fibers, but its detailed mechanism remains a matter of controversy. The effect of cyclic tensile load on the metabolism of the anterior cruciate ligament were investigated experimentally using cultured cells from the anterior cruciate ligament of rabbits. Using culture plates with flexible rubber bases, a cyclic tensile load was applied to the cultured cells for 24 hours, and the changes in shape, alignment, and metabolism of the cells were analyzed. Under the cyclic tensile load, the shape of the cells from the anterior cruciate ligament changed to spindle and aligned perpendicularly to the direction of the tensile load. The cyclic tensile load also caused an increase in collagen synthesis by the cells from the anterior cruciate ligament, which was predominant in Type I. The cells from the synovium showed similar changes in shape and alignment under the cyclic tensile load, but no significant change was observed in cell metabolism. These observations suggest that the application of cyclic tensile load on the anterior cruciate ligament cells is an important factor in the regulation of collagen synthesis in the anterior cruciate ligament.

Animals↗
PubMed1998

High production of nondisjunction mutants in the offspring of Drosophila melanogaster females exposed to carbon dioxide at meiosis I.

Drosophila melanogaster females homozygous for X-linked recessive markers, y and wi, were exposed to CO2 and mated with y+ w+/Y males. The progeny were sampled and inspected for y wi/y wi/Y (XXY) and y+ w+/O (XO) mutants. The frequency of nondisjunction XXY mutants after a 90-min exposure to CO2 increased 100-fold above the control level in the first-day brood but did not increase above the control level in the second to sixth broods, showing that CO2 is an extremely potent inducer of nondisjunction in mature oocytes during meiotic metaphase I but is not harmful to immature oocytes. Nondisjunction-causing damage induced by CO2 in mature oocytes disappeared completely within one day after CO2 treatment, as evidenced by a reduction of the number of XXY mutants to the control level when the mating of CO2-treated females was delayed by one day. CO2-induced nondisjunction is probably due to damage to spindle microtubules in mature oocytes at metaphase I. N2 is a less potent inducer of nondisjunction than CO2. Maternal X-irradiation with 4 Gy did not induce XXY mutants, showing that medium-level radiation does not induce nondisjunction. The results support Gaulden's hypothesis that oxygen deficits and CO2 increases in the microenvironment of mature oocytes can be potent inducers of nondisjunction. The possible relationship to the cluster of Down syndrome seen in Berlin shortly after the Chernobyl accident is discussed.

Aneuploidy↗
PubMed1997

Characterization of the precursor of prostate-specific antigen. Activation by trypsin and by human glandular kallikrein.

The precursor or zymogen form of prostate-specific antigen (pro-PSA) is composed of 244 amino acid residues including an amino-terminal propiece of 7 amino acids. Recombinant pro-PSA was expressed in Escherichia coli, isolated from inclusion bodies, refolded, and purified. The zymogen was readily activated by trypsin at a weight ratio of 50:1 to generate PSA, a serine protease that cleaves the chromogenic chymotrypsin substrate 3-carbomethoxypropionyl-L-arginyl-L-prolyl-L-tyrosine-p-nitroanili ne- HCl (S-2586). In this activation, the amino-terminal propiece Ala-Pro-Leu-Ile-Leu-Ser-Arg was released by cleavage at the Arg-Ile peptide bond. The recombinant pro-PSA was also activated by recombinant human glandular kallikrein, another prostate-specific serine protease, as well as by a partially purified protease(s) from seminal plasma. The recombinant PSA was inhibited by alpha1-antichymotrypsin, forming an equimolar complex with a molecular mass of approximately 100 kDa. The recombinant PSA failed to activate single chain urokinase-type plasminogen activator, in contrast to the recombinant hK2, which readily activated single chain urokinase-type plasminogen activator. These results indicate that pro-PSA is converted to an active serine protease by minor proteolysis analogous to the activation of many of the proteases present in blood, pancreas, and other tissues. Furthermore, PSA is probably generated by a cascade system involving a series of precursor proteins. These proteins may interact in a stepwise manner similar to the generation of plasmin during fibrinolysis or thrombin during blood coagulation.

Enzyme Activation↗
PubMed1997

Histologic characteristics of renal cell carcinomas with lymph node metastasis.

BACKGROUND: This study was conducted to determine if there are any specific histologic features that are associated with lymph node metastasis in renal cell carcinoma (RCC). METHODS: TNM classification, histologic grade, mean nuclear volume, cell type, and histologic architecture of the tumors were evaluated in 66 patients who had undergone nephrectomy and lymphadenectomy for RCC. In the 18 patients with positive lymph node metastasis, both primary lesions and metastatic lymph nodes were evaluated. RESULTS: Lymph node status was correlated with primary tumor stage, venous involvement, and distant metastasis. The tumor grade was higher, and the mean nuclear volume was larger, in both primary and metastatic lesions of RCCs with lymph node metastasis than in tumors with no metastasis. In primary lesions of RCCs with lymph node metastasis, clear cell, alveolar, or cystic patterns were observed less frequently, and granular or spindle/pleomorphic cells and papillary or solid patterns, were observed more frequently, as compared to those lesions without metastasis. Comparison between primary and metastatic lesions in individual patients revealed no significant difference in grade or mean nuclear volume. The development of new cell types or histologic architectures, which was not noted in the primary lesions, was also a rare event in the metastatic lesions. CONCLUSION: Several characteristic histologic features, which may reflect the increased metastatic potential of the tumor, were observed in both primary and metastatic lesions in cases of RCC with lymph node metastasis. No substantial difference in histologic features was observed between the primary or metastatic lesions of individual patients.

Adolescent↗
PubMed1997

Intratumoral heterogeneity in prostate cancer demonstrated by volume-weighted mean nuclear volume.

This study was conducted to investigate the degree of heterogeneity of the volume-weighted mean nuclear volume (MNV) calculated from radical prostatectomy specimens, and to evaluate how closely the MNV calculated from transrectal biopsy specimens reflected the overall malignancy. MNV was evaluated using 77 sections of histological specimens from 9 patients who underwent radical prostatectomy at Shizuoka City Hospital between January 1990 and December 1995. The MNV values calculated from radical prostatectomy specimens were compared with those calculated from preoperative transrectal biopsy specimens. MNV was judged to be homogeneous in six cases and heterogeneous in three cases. Of the heterogeneous cases, MNV calculated from the transrectal biopsy specimens was judged to be underestimated in 2 of 3 cases. This study shows that intratumoral heterogeneity of prostate cancer may affect clinical estimates of the grade of malignancy based on the MNV, and indicates the need for a sufficient number of specimens in order to evaluate the MNV by transrectal biopsy.

Adenocarcinoma↗
PubMed1997

Role of volume weighted mean nuclear volume for predicting disease outcome in patients with renal cell carcinoma.

PURPOSE: Histological grading of malignancy in renal cell carcinoma is based on qualitative, morphological examination and suffers from poor reproducibility. On the other hand, estimate of volume weighted mean nuclear volume, which was developed based on a stereological technique, is an easy method to perform with high reproducibility. Furthermore, it has been reported that mean nuclear volume is remarkably correlated with prognosis of bladder and prostate cancer. We compared mean nuclear volume to a histological grading method and TNM classification in determining the prognosis of renal cell carcinoma using a Cox proportional hazards model. MATERIALS AND METHODS: A retrospective, prognostic study was done of 65 patients with renal cell carcinoma diagnosed by radical nephrectomy or needle punch biopsy between January 1978 and November 1995. Unbiased estimates of mean nuclear volume were compared to TNM classification and histological grading to determine prognostic value. RESULTS: Univariate analysis indicated that all TNM classifications, histological grades and estimates of mean nuclear volume were significantly correlated with prognosis of renal cell carcinoma. However, multivariate analysis revealed that estimates of mean nuclear volume and metastasis at diagnosis were the 2 most powerful independent predictors of disease specific survival. CONCLUSIONS: Our results indicate that estimates of mean nuclear volume are prognostically superior to morphological grading of renal cell carcinoma. We recommend mean nuclear volume estimates as an adjunct to subjective histological grading in patients with this disease.

Carcinoma, Renal Cell↗