Human adipose tissue-derived stromal cells can differentiate into megakaryocytes and platelets by secreting endogenous thrombopoietin.

UNLABELLED: Essentials Manufacturing platelets from a donor-independent source is highlighted in transfusion medicine. We examined the differentiation of adipose tissue-derived stromal cells (ASCs) into platelets. Endogenous thrombopoietin (TPO) induced ASCs differentiation into megakaryocytes and platelets. TPO secretion from ASCs was due to an interaction of transferrin with its receptor CD71. SUMMARY: Background Ex vivo production of megakaryocytes (MKs) and platelets from a donor-independent source is currently of intense interest in transfusion medicine. Adipose tissue-derived stromal cells (ASCs) constitute an attractive candidate cell source, because inducing these cells into MK lineages requires no gene transfer and only endogenous transcription factors containing p45NF-E2/Maf, an MK-inducing factor. Objectives To examine whether ASCs differentiate into MK lineages by using endogenous thrombopoietin (TPO), a primary cytokine that drives MK lineages. Methods TPO levels were measured by quantitative real-time PCR and ELISA. To investigate the effects of endogenous TPO on MK and platelet production, surface marker expression and functions for platelets were analyzed in ASC-derived cells cultured in the presence or absence of recombinant TPO. Based on a screening test, the role of transferrin receptor CD71 in TPO production and MK differentiation was examined with anti-CD71 antibody, small interfering RNA (siRNA) against CD71 (siRNA-CD71), and CD71-positive/negative cells. Results ASCs secreted TPO during MK differentiation, and the endogenous TPO facilitated MK and platelet production from ASCs. TPO secretion from ASCs occurred in a transferrin-dependent manner. ASCs treated with anti-CD71 antibody or transfected with siRNA-CD71 produced markedly less TPO. The TPO levels and MK yield were significantly higher when CD71-positive ASCs were used than when CD71-negative ASCs were used. Conclusions CD71 might be an appropriate marker for MK progenitor cells among human ASCs, because of the higher capacity of CD71-positive cells to produce TPO and their ability to differentiate into MKs. These findings could help to establish an efficient method for platelet production.

Recurrent vesical calculi, hypercalciuria, and biochemical evidence of increased bone resorption in an adult male with paraplegia due to spinal cord injury: is there a role for intermittent oral disodium etidronate therapy for prevention of calcium phosphate bladder stones?

STUDY DESIGN: Clinical case report with comments by colleagues from Sweden, Poland, Spain, Brazil, Japan, Belgium and Switzerland. OBJECTIVES: To discuss the role of disodium etidronate therapy for prevention of calcium phosphate vesical calculi in persons with spinal cord injury, who have hypercalciuria and biochemical evidence of increased bone resorption. SETTING: Regional Spinal Injuries Centre, Southport, UK. METHODS: A 21-year-old male sustained paraplegia (T-10; ASIA scale: A) in a road traffic accident in June 2001. He had an indwelling urethral catheter until the end of August 2001, when he started self-catheterisation. He developed bladder stones and electrohydraulic lithotripsy (EHL) was performed in May 2002. All stone fragments were removed. Recurrence of vesical calculi was noted in October 2002. These stones were fragmented by lithoclast lithotripsy in two sessions, in December 2002 and February 2003; all stone fragments were removed at the end of the second session. This patient reverted to indwelling catheter drainage when vesical calculi recurred. In September 2003, X-ray of the abdomen showed recurrence of vesical calculi. By February 2004, the stones had increased in size and number. EHL of vesical calculi was again performed in April 2004. Complete clearance was achieved. RESULTS: A 24-h urinalysis detected hypercalciuria--18.7 mmol/day (reference range: 2.5-7.5). Biochemical analysis of vesical calculus revealed calcium phosphate (85%) and magnesium ammonium phosphate (15%). Plasma C-terminal telopeptide (CTX) was increased - 1.06 ng/ml (reference range: 0.1-0.5 ng/ml). Free deoxypyridinoline/creatinine ratio (fDPD/Cr) in urine was also increased - 20.2 (reference range: 2.3-5.4). In April 2004, this patient was prescribed disodium etidronate 400 mg day. Nearly 3 months after commencing therapy with etidronate, plasma CTX decreased to 0.87 ng/ml. fDPD/Cr in urine also decreased to 12.4. After 4 months of etidronate therapy, 24-h urinary calcium excretion had decreased to 6.1 mmol/day. CONCLUSION: Etidronate (400 mg daily) is a very effective inhibitor of calcium phosphate crystallisation. Etidronate decreased urinary excretion of calcium, an important factor in prevention of calcium phosphate bladder stones. Etidronate therapy is not a substitute for other well-established methods for prevention of vesical calculi in spinal cord injury patients, for example, large fluid intake, avoiding long-term catheter drainage. Intermittent therapy with etidronate may be considered in selected patients, in whom hypercalciuria persists after instituting nonpharmacological therapy for an adequate period, for example, early mobilisation, weight-bearing exercises, and functional electrical stimulation. However, possible side effects of etidronate, and the fact that etidronate is not licensed in United Kingdom for prevention of urolithiasis, should be borne in mind.

Intravesical combined chemoimmunotherapy with epirubicin and bacillus Calmette-Guérin is not indicated for superficial bladder cancer.

PURPOSE: The short-term effects of intravesical chemoimmunotherapy with epirubicin and bacillus Calmette-Guérin (BCG) administered repeatedly for prophylaxis of recurrence of superficial bladder cancer (pTa, pT1) were investigated in 24 patients aged a median of 70 years between March 1996 and February 1999, and were compared with those of BCG monotherapy in 50 patients from March 1990 to February 1999. PATIENTS AND METHODS: The patients underwent intravesical instillation of the Tokyo strain BCG with or without epirubicin after transurethral resection (TUR) of bladder cancer. For the combined treatment, at 1-2 weeks after TUR, epirubicin (40 mg) and BCG (80 mg) were istilled into the bladder by turns once a week for 12 weeks. For the group receiving only BCG, 80-mg instillations were done with the same schedule. Thereafter, the patients were followed by cystoscopy and urinary cytology every 3 months for up to 3 years after intravesical therapy. RESULTS AND CONCLUSIONS: At 2 years after treatment, the simple recurrence rate was 26.1% (6/23) in patients with chemoimmunotherapy and 32.0% (16/50) in BCG-treated patients. Adverse reactions, including increased frequency of urination, urgency and miction pain, were observed in 18 patients (85.7%) undergoing chemoimmunotherapy and 58.0% undergoing BCG monotherapy. One patient receiving chemoimmunotherapy was withdrawn from treatment because of symptoms of severe bladder irritation due to the instillation. Intravesical chemoimmunotherapy using epirubicin and BCG was finally found to be inferior in comparison with BCG monotherapy for the prophylaxis of recurrence of superficial bladder cancer.

Functions and ATP-binding responses of the twelve histidine residues in the TF1-ATPase beta subunit.

The C2 proton signals of all (twelve) histidine residues of the TF1 beta subunit in the 1H-NMR spectrum have been identified and assigned by means of pH change experiments and site-directed substitution of histidines by glutamines. pH and ligand titration experiments were carried out for these signals. Furthermore, the ATPase activity of the reconstituted alpha3beta3gamma complex was examined for the twelve mutant beta subunits. Two of three conserved histidines, namely, His-119 and 324, were found to be important for expression of the ATPase activity. The former fixes the N-terminal domain to the central domain. His-324 is involved in the formation of the interface essential for the alpha3beta3gamma complex assembly. The other conserved residue, His-363, showed a very low pK(a), suggesting that it is involved in the tertiary structure formation. On the binding of a nucleotide, only the signals of His-173, 179, 200, and 324 shifted. These histidines are located in the hinge region, and its proximity, of the beta subunit. This observation provided further support for the conformational change of the beta monomer from the open to the closed form on the binding of a nucleotide proposed by us [Yagi et al. (1999) Biophys. J. 77, 2175-2183]. This conformational change should be one of the essential driving forces in the rotation of the alpha3beta3gamma complex.

Tubularized incised-plate urethroplasty for secondary hypospadias surgery.

PURPOSE: Reoperation for failed hypospadias has been considered to be seriously bothersome because abundant penile skin does not tend to remain for urethroplasty or for penile shaft skin coverage. In this study, the tubularization of incised urethral plate was employed for those who had no excessive penile skin after failure of hypospadias repair. METHODS: Five patients with hypospadias underwent tubularized incised-plate urethroplasty as salvage surgery. The surgical techniques necessary for the performance of the reoperation were not different from those for the primary repair. The urethral plate was incised sufficiently deeply in its midline from the tip of the glans to the regressed meatus. The incised urethral plate was tubularized without tension over a catheter of an appropriate size. RESULTS: Four of those who underwent secondary tubularized incised-plate urethroplasty were successfully repaired without complications. A urethrocutaneous fistula occurred at the corona in the remaining patient. CONCLUSIONS: The absence of preputial skin in reoperative cases makes tubularized incised-plate urethroplasty the ideal option, although the series was small and postoperative duration is still short. In addition, this procedure can give excellent functional and cosmetic results even in patients who require revisional hypospadias surgery.

Human prostate cancer cells adhere specifically to hemoglobin: a possible role in bone-specific metastasis.

From the supernatant of rabbit bone marrow, we isolated an organ-specific factor, which was related with the metastasis of prostate cancer to the bone and examined its adhesion to prostate cancer cells (PC-3). Molecular weight and amino acid sequence analyses of the active component obtained by high performance liquid chromatography revealed that a component identical to the alpha chain of hemoglobin accounted for 80% of the biological activity. Hemoglobin showed over 50% adhesion to PC-3 cells but only 10% adhesion to human colon cancer cell lines, representative of organ non-specific metastasis, and leukemia cells line, representative of a non-solid tumor. Some substance in the bone marrow may promote the first step of adhesion of cancer cells to bone marrow in the metastasis of prostate cancer to the bone, possibly an amino acid sequence or some tertiary structure similar to hemoglobin.

S-Adenosyl-L-methionine-dependent O-methylation of 2-hydroxy-3-alkylpyrazine in wine grapes: a putative final step of methoxypyrazine biosynthesis.

The final step of 2-methoxy-3-alkylpyrazine (MP) biosynthesis has been presumed to involve O-methylation of 2-hydroxy-3-alkylpyarzine (HP), although this reaction has never been demonstrated in organisms. We detected 2-hydroxy-3-isobutylpyrazine (IBHP) and 2-hydroxy-3-isopropylpyrazine (IPHP) in unripe grapes, and S-adenosyl-L-methionine-dependent O-methyltransferase (OMT) activity toward HP in crude extracts from young shoots and unripe grapes that accumulate MP at different levels. The levels of HP in the berries and stems were estimated by using 2-hydroxy-3-sec-butylpyrazine as an internal standard. The OMT activity observed in the crude extracts from young shoot and berries was extremely low, but no MP-decomposing activity was detected in the solutions. The levels of HP and OMT activity were closely related with the level of MP in the grapes. These results indicate that the predicted final step of MP biosynthesis exists in wine grapes.

[A case of recurrent lung cancer successfully treated with vinorelbine and cisplatin].

A 56-year-old female underwent lobectomy with ND2a lymph node dissection for left lung cancer in April 1999. Histopathological examination demonstrated moderately differentiated adenocarcinoma (pT2N2M0, stage III A). She received one course of a combination of etoposide and cisplatin as adjuvant therapy, followed by oral intake of UFT. In November 1999, a left para-aortic lymph node recurrence was found. She received radiation therapy (total 60 Gy) to the mediastinum. In April 2000, new lung and left supraclavicular lymph node recurrences were found. She received three courses of vinorelbine 20 mg/m2 (days 1, 8) and cisplatin 80 mg/m2 (day 1) followed by radiation therapy (total 50.4 Gy) to the left supraclavicular lesion. After the chemotherapy, a complete response (CR) of all metastatic lesions was achieved. Adverse reactions were grade 1 alopecia, grade 2 nausea/vomiting, grade 3 neutropenia, hypochromia, and injection site reaction. The combination of vinorelbine and cisplatin is a useful regimen in non-small-cell lung cancer.

One-stage repair of moderately severe hypospadias using a transverse preputial tubularized island flap.

BACKGROUND: Transverse preputial tubularized island flap (TPTIF) urethroplasty has been used for the repair of moderately severe hypospadias since Duckett described the procedure in 1980. In spite of the excellent results reported by Duckett, subsequent studies showed high complication rates. A TPTIF procedure modified to reduce the complication rate is presented. METHODS: Between 1996 and 1997, 13 boys with moderately severe hypospadias were repaired with the TPTIF procedure. Patient age ranged from 10 months to 3 years with an average age of 23 months. To prevent urethrocutaneous fistula, the neourethra was constructed with a two-layer closure and the portion of anastomosis was wrapped between the native urethra and the neourethra with the tissue of the corpus spongiosum. RESULTS: The moderately severe hypospadias was repaired without complication in 12 of 13 patients. A urethrocutaneous fistula developed at the midshaft of the penis in one patient. No meatal stenosis, urethral stricture or diverticulum developed. CONCLUSION: Transverse preputial tubularized island flap urethroplasty provided excellent cosmetic and functional results for moderately severe hypospadias, and postoperative complications could be decreased by the two-layer closure of the neourethra and application of the wrapping technique of the proximal anastomosed portion with corpus spongiosum tissue.

Primary and salvage urethroplasty using Mathieu meatal-based flip-flap technique for distal hypospadias.

BACKGROUND: Numerous surgical procedures have been attempted for correction of distal hypospadias. The Mathieu procedure was employed in this study for secondary cases as well as primary cases. METHODS: The length of the skin flap is determined by measuring the distance from the meatus to the glans tip and then the ventral meatal-based skin flap is incised. The proximal skin flap is flipped and anastomosed to the distal urethral plate. Additionally, subcutaneous tissue of the flipped flap is sutured to cover the original suture lines completely. RESULTS: The Mathieu urethroplasty was successful in one stage in 13 of the 16 primary repair cases (81%). Twelve of the 13 (92%) who underwent a secondary Mathieu procedure were successfully repaired with no problems. An overall success rate of 86% was achieved at the first operation for both primary and secondary cases. In the remaining 14% of the cases, success was achieved with only one additional procedure. CONCLUSIONS: The Mathieu flip-flap procedure is feasible for relatively short urethral defects if the ventral penile skin demonstrates adequate mobility and there is no chordee. Even in patients who require revisional hypospadias surgery, the Mathieu procedure can give excellent functional and cosmetic results.

KAI1 expression can be a predictor of stage A prostate cancer progression.

The disease progression and rate of cancer death were analyzed in 52 patients with stage A prostate cancer who underwent transurethral resection of the prostate (TURP) or retropubic subcapsular prostatectomy (SCP) between 1987 and 1998. We performed immunohistochemistry on 16 patients to determine the correlation between the expression of the tumor metastasis suppressor gene KAI1 and the subsequent progression of stage A prostate cancer. Nineteen and 33 of the patients had cancer at stage A1 and stage A2, respectively, and their subsequent courses were followed for an average of 53.7 months (24-134 months). Progression to clinical cancer was found in six patients (one with stage A1, and five with stage A2). This progression was evident 40.8 months (5-80 months) after TURP or SCP. Four (66.7%) of the patients died of cancer progression (average 31 months) after prostatectomy. All four patients had stage A2, poorly differentiated adenocarcinoma, and had been followed with administration of diethylstilbestrol diphosphate (DES-P). The disease-free patients (n=10) showed overexpression of KAI1 protein, compared to those with disease progression (n=6). These results indicate that progression arose mainly in the patients with stage A2 cancer, and that poorly differentiated, focal and weak expression of KAI1 protein is highly associated with disease progression. It is suggested that patients in this group should be treated with immediate total androgen blockade, radiation, or radical prostatectomy after diagnosis.Prostate Cancer and Prostatic Diseases (2001) 4, 150-153.

Purification and characterization of a O-methyltransferase capable of methylating 2-hydroxy-3-alkylpyrazine from Vitis vinifera L. (cv. Cabernet Sauvignon).

An S-adenosyl-L-methionine-dependent O-methyltransferase capable of methylating 2-hydroxy-3-alkylpyrazine (HP) was purified 7,300-fold to apparent homogeneity with an 8.2% overall recovery from Vitis vinifera L. (cv. Cabernet Sauvignon) through a purification procedure including column chromatography on DEAE-Sepharose FF, Ether-5PW, hydroxyapatite, G2000SW(XL), and DEAE-5PW. The relative molecular mass of the native enzyme estimated on gel permeation chromatography was 85 kDa, and the subunit molecular mass was estimated to be 41 kDa on SDS-polyacrylamide gel electrophoresis. The enzyme also methylates caffeic acid. The Vmax for IBHP and caffeic acid were 0.73 and 175 pkatals/mg, respectively, and the respective Km for IBHP and caffeic acid were 0.30 and 0.032 mm. The optimum pH for IBHP (8.5) was different from that for caffeic acid (7.5).

Solitary fibrous tumor of the peritoneum found in the prevesical space.

Solitary fibrous tumors (SFT) are well recognized in the pleura, but their rare occurrence at other sites has become appreciated only in recent years. We experienced a 68-year-old male patient who presented with frequency of urination and difficulty in voiding. Computed tomographic scan revealed a solid and cystic mass which measured 12 x 10 cm in the prevesical space. This tumor showed typical histopathologic features of SFT, and was immunostained positive for vimentin, CD34 and CD99. This is an extremely rare case of SFT arising from the parietal peritoneum found in the prevesical space.

Aberration of chromosomes 8 and 11 in bladder cancer as detected by fluorescence in situ hybridization.

Although a bladder cancer-specific abnormality in chromosomes or genes has not been reported, chromosomal regions that tend to become abnormal have been recognized. In this study, we investigated abnormalities in chromosomes 8 and 11. There were 27 patients with bladder cancer, 16 males and 11 females, who participated in this study. Abnormalities in chromosomes 8 and 11 were investigated by the fluorescence in situ hybridization (FISH) method. Probes used in this study were chromosome 8 alpha-satellite and chromosome 11 alpha-satellite (Oncor Co.). Of 27 cases, 15 cases were positive for chromosome 8 (55.6%) and ten cases were positive for chromosome 11 (37.0%). Since the FISH method detects chromosomal abnormality by the number of signals generated in cancer cells, this method is objective and simple and thus may be applicable in clinical practice.

Clinical features of primary hyperparathyroidism: preoperative localization and parathyroidectory.

The introduction of the multichannel autoanalyser made measurement of serum calcium concentrations easier, and led to a dramatic change in clinical presentations. The reliable methods such as computed tomography (CT), ultrasonography (US) and magnetic resonance imaging (MRI) for preoperative localization of abnormal parathyroid glands has long been sought to increase the cure rate of surgical treatment. We report the clinical feature of primary hyperparathyroidism (PHPT). Patients were classified into four stages in chronological order. The early patients (the first stage, 1970-1979) were mainly diagnosed in the treatment of urolithiasis. Approximately 20% of patients in the second stage (1980-1986) were symptom-free, and hypercalcemia was detected by autoanalyzer. Patients in the third stage (1987-1993) underwent preoperative localization studies including CT. scintigraphy, ultrasonography and MRI. The recent patients (the fourth stage, 1993-1999) were mostly treated in the present hospital. In the first stage, PHPT was an uncommon metabolic disorder hat was typically associated with nephrolithiasis and was two to three times more common in men than in women. In the second, third and fourth stages, PHPT is a common and often symptomless endocrine disorder. The ratio of male to female is decreasing, because men are dominant in stone-formers. Four parathyroid glands were searched carefully in the first and second stages, and unilateral cervical exploration was performed in some preoperatively localized parathyroid glands in the third and fourth stages.

Depolarization-associated iron release with abrupt reduction in pulmonary endothelial shear stress in situ.

This study evaluated the roles of endothelial cell membrane potential and reactive oxygen species (ROS) in the increase of tissue free iron during lung ischemia. Oxygenated ischemia was produced in the isolated rat lung by discontinuing perfusion while ventilation with O2 was maintained. We have shown previously that tissue oxygenation is maintained in this model of ischemia and that biochemical changes are the result of an abrupt reduction in endothelial shear stress. With 1 hr oxygenated ischemia, generation of ROS, evaluated by oxidation of dichlorodihydrofluorescein (H2DCF) to fluorescent dichlorofluorescein, increased 8.0-fold, lung thiobarbituric acid reactive substances (TBARS) increased 3.4-fold, and lung protein carbonyl content increased 2.4-fold. Lung tissue free iron, measured in the lung homogenate with a fluorescent desferrioxamine derivative, increased 4.0-fold during ischemia. Pretreatment of lungs with thapsigargin abolished the increase in free iron with ischemia indicating that this effect is dependent on Ca2+ release from intracellular stores. Perfusion of lungs with high (25 mM) K+ to depolarize the endothelium also led to a significant increase in tissue free iron. Pretreatment of lungs with 35 microM cromakalim, a K+-channel agonist, significantly inhibited both ischemia-induced tissue oxidant injury and the increase in free iron with ischemia or with high K+ perfusion. A similar increase in free iron was observed when lungs were ventilated with either O2 or N2 during the ischemic period or were pre-perfused with an inhibitor of ROS production (diphenyleneiodonium). These results indicate that ROS generation is not required for ischemia-mediated iron release. Thus, ROS generation and iron release with ischemia are independent although both are subsequent to endothelial cell membrane depolarization.

Intravascular origin of metastasis from the proliferation of endothelium-attached tumor cells: a new model for metastasis.

Metastasis is a frequent complication of cancer, yet the process through which circulating tumor cells form distant colonies is poorly understood. We have been able to observe the steps in early hematogenous metastasis by epifluorescence microscopy of tumor cells expressing green fluorescent protein in subpleural microvessels in intact, perfused mouse and rat lungs. Metastatic tumor cells attached to the endothelia of pulmonary pre-capillary arterioles and capillaries. Extravasation of tumor cells was rare, and it seemed that the transmigrated cells were cleared quickly by the lung, leaving only the endothelium-attached cells as the seeds of secondary tumors. Early colonies were entirely within the blood vessels. Although most models of metastasis include an extravasation step early in the process, here we show that in the lung, metastasis is initiated by attachment of tumor cells to the vascular endothelium and that hematogenous metastasis originates from the proliferation of attached intravascular tumor cells rather than from extravasated ones. Intravascular metastasis formation would make early colonies especially vulnerable to intravascular drugs, and this possibility has potential for the prevention of tumor cell attachment to the endothelium.

Functional conformation changes in the TF(1)-ATPase beta subunit probed by 12 tyrosine residues.

The effect of nucleotide binding on the structure of the F(1)-ATPase beta subunit from thermophilic bacillus PS-3 (TF(1)beta) was investigated by monitoring the NMR signals of the 12 tyrosine residues. The 3,5-proton resonances of 12 tyrosine residues could be observed for the specifically deuterated beta subunit. The assignment of 3,5-proton resonances of all of the tyrosine residues was accomplished using 14 mutant proteins, in each of which one or two tyrosine residues were replaced by phenylalanine. Binding of Mg. ATP induced an upfield shift of Tyr(341) resonance, suggesting that their aromatic rings are stacked to each other. Besides Tyr(341), the signal shift observed on Mg.ATP binding was restricted to the resonances of Tyr(148), Tyr(199), Tyr(238), and Tyr(307), suggesting that Mg.ATP induces a conformational change in the hinge region. This can be correlated to the change from the open to closed conformations as implicated in the crystal structure. Mg.ADP induced a similar but distinctly different conformational change. Therefore, the intrinsic conformational change in the beta subunit induced by the nucleotide binding is proposed to be one of the essential driving forces for the F(1) rotation. Reconstitution experiments showed that Tyr(277), one of the four conserved tyrosines, is essential to the formation of the alpha(3)beta(3)gamma complex.

Osteopontin expression in prostate cancer and benign prostatic hyperplasia.

OBJECTIVES: Osteopontin (OPN), a secreted adhesive glycoprotein, has been shown to be produced in excessive amounts in a variety of experimental models of malignancy. Increased levels of OPN exist in blood from the lungs, breasts, and gastrointestinal tracts of cancer patients with metastases. However, there have been no reports on the expression of OPN in human urological malignancies. The present study investigates the presence of OPN in adenocarcinoma of the human prostate and in benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Using prostate tissue from 34 patients with primary prostate cancer, 13 patients with prostate cancer after having undergone hormonal therapy, and 12 patients with BPH, formalin-fixed paraffin sections were prepared. Specimens were obtained by needle biopsy or radical prostatectomy. Immunohistochemical staining (ABC method) was then performed. Staining was divided into either negative or positive categories. RESULTS: Positive staining of OPN was observed on cancer cells and macrophages in 52.9% of the primary prostate cancers and 14.5% of the prostate cancers after hormonal therapy. In BPH specimens, 66.7% of the cases displayed positive staining of OPN. The staining level of OPN showed no correlation with serum prostate-specific antigen, but did correlate with stage, differentiation, and Gleason's score. CONCLUSIONS: The result postulates that the expression of OPN is an indicator of cell differentiation; however, it cannot be used as a marker of malignancy in prostate cancer.