Evaluation of Color-matching Ability of a Structural Colored Resin Composite.

PURPOSE: The present study evaluated the color-matching ability of a structural colored resin composite to compare it with resin composites employing pigments. METHODS AND MATERIALS: A structural colored resin composite (Omnichroma [OMC]), a supranano-filled resin composite (Estelite ∑ Quick [ELQ]), and a nano-filled resin composite (Filtek Supreme Ultra [FSU]) were used. Each resin composite was packed into a Teflon mold and pressed down with a clear strip under a glass slide. The specimens were light irradiated through the slide with a light-emitting diode curing unit. The thickness of the specimens (n=6) was measured with a digital caliper before being transferred to distilled water and stored at 37°C for 24 hours. The measurements of the optical characteristics of the specimens on a black-and-white background were performed using a spectrophotometer. D65 (CIE D65) was used as a light source for the spectrophotometer. Measurements were repeated three times for each specimen under each color-measurement condition, and average values for three same-shade specimens were calculated. One-way analysis of variance and Tukey post hoc tests were used (α=0.05). To determine its ability to match the color of artificial teeth, each shade of resin composite was placed in a cavity before performing color measurements. Using a spectrophotometer (CMS-35F S/C) with a flexible sensor, L*, a*, and b* values were obtained. RESULTS: The spectral reflectance curve of OMC showed that it reflected light wavelengths from 430-700 nm regardless of the background color and thickness of the specimens. The percentage of reflectance of ELQ decreased near wavelengths of 550-580 nm. Regarding the influence of background color on CIE L*, a*, b* values, the L* level showed significantly higher values for all tested materials with white backgrounds, and OMC was most affected by the difference in background color. However, a* values of ELQ and FSU were significantly higher with a black background than with a white background, and OMC showed a significantly higher value with a white background than with a black background. The b* values were higher with a white background than with a black background and were significantly higher for all three products, and these tendencies were much greater for ELQ and FSU. CONCLUSIONS: The ability of OMC to match the color of artificial teeth showed acceptable color compatibility, regardless of the shade of the artificial teeth and the depth of the cavity. However, ELQ and FSU showed reduced color compatibility, especially for a cavity depth of 3.0 mm. Excellent color matching ability was confirmed for the structural colored resin composite OMC, resulting in reduced color differences and therefore improving the esthetic appearance of the restoration, simplifying shade matching, and compensating for any color mismatch.

Functional role of ALK-related signal cascades on modulation of epithelial-mesenchymal transition and apoptosis in uterine carcinosarcoma.

BACKGROUND: Anaplastic lymphoma kinase (ALK), which is a receptor tyrosine kinase, is essentially and transiently expressed in the developing nervous system. Recently, the deregulated expression of full-length ALK has been observed in some primary solid tumors, but little is known about its involvement in the tumorigenesis of uterine carcinosarcomas (UCSs). Here we examined the functional role of the ALK gene in UCSs. METHODS: Regulation and function of the ALK gene were assessed using two endometrial carcinoma cell lines. Expression of ALK and its related molecules were also investigated using clinical samples of UCSs. RESULTS: In cell lines, ALK promoter activity was significantly increased by transfection of Sox11 and N-myc, which are known to contribute to neuronal properties. Cells stably overexpressing full-length ALK showed an enhancement of EMT properties mediated by TGF-ß1 and HGF, along with an increase in phosphorylated (p) Akt and nuclear p65. Overexpression of p65 also led to transactivation of Twist1 gene, known as an EMT inducer. Finally, treatment of the stable ALK-overexpressing cells with doxorubicin resulted in inhibition of apoptosis with progressive increase in the expression ratio of both pAkt and bcl2 relative to total Akt and bax, respectively. In clinical samples, strong cytoplasmic ALK immunoreactivity and mRNA signals without rearrangement or amplification of the ALK locus were frequently observed in UCSs, particularly in the sarcomatous components. Further, ALK IHC score was found to be positively correlated with Sox11, N-myc, Twist1, and bcl2 scores. CONCLUSION: ALK-related signal cascades containing Akt, NF-κB, Twist1, and bcl2 may participate in initial signaling for divergent sarcomatous differentiation driven from carcinomatous components in UCSs through induction of the EMT process and inhibition of apoptotic features.

Transcription factor Egr1 acts as an upstream regulator of beta-catenin signalling through up-regulation of TCF4 and p300 expression during trans-differentiation of endometrial carcinoma cells.

The beta-catenin/TCF4/p300 pathway is involved in early signalling for trans-differentiation towards the morular phenotype of endometrial carcinoma cells, but little is known about the upstream regulators. Here we show that transcription factor early growth response 1 (Egr1) acts as an initial mediator through up-regulating the expression of TCF4 and p300. In an endometrial carcinoma cell line with abundant oestrogen receptor alpha, Egr1 expression at both mRNA and protein levels was significantly increased by serum and 17beta-oestradiol stimuli. Serum-stimulated cells also showed increased expression of TCF4 and p300, while inhibition of Egr1 by specific siRNAs resulted in decreased expression. Transfection of Egr1 led to transactivation of TCF4 as well as p300 genes, through specific binding to a promoter region, and thus in turn resulted in nuclear accumulation of beta-catenin mediated by the up-regulating TCF4. The overexpression also caused inhibition of beta-catenin/TCF4/p300-mediated transcription, probably through sequestration of p300. Egr1 promoter activity was increased by serum but not 17beta-oestradiol, in contrast to the marked repression associated with TCF4, p300, and Egr1 itself, indicating that the regulation involves several feedback loops. In clinical samples, cells immunopositive for nuclear Egr1, as well as beta-catenin and TCF4, were found to be sporadically distributed in glandular components of endometrial carcinoma with morules. A significant positive correlation between nuclear beta-catenin and TCF4 was observed, but no such link was evident for Egr1, probably due to the existence of negative feedback regulation. Together, these data indicate that Egr1 may participate in modulation of the beta-catenin/TCF4/p300 signalling pathway as an initial event during trans-differentiation of endometrial carcinoma cells, through its impact on several signalling networks.

Diagnostic and prognostic significance of cyclin A expression in low-grade astrocytomas: comparison with astrogliosis and high-grade tumours.

AIM: Definitive distinction between low-grade astrocytoma and astrogliosis is a long-standing difficulty due to their similar histopathological characteristics. To clarify differences in biological significance, this study focused on various components of the cell cycle machinery and proliferation as key parameters, comparing expression in astrogliosis, as well as low- and high-grade astrocytomas. METHODS: The expression of p16, p21 and p27, and cyclin A, cyclin D1, cyclin E, Rb and Ki-67 was immunohistochemically examined in 40 cases of astrogliosis and 48 cases of low-grade astrocytomas (grade II), as well as 50 high-grade tumours (grades III and IV). The results were also compared with survival data for the astrocytomas. RESULTS: Cell proliferation determined by Ki-67 immunoreactivity did not differ between astrogliosis and low-grade tumours. Average labelling indices (LIs) for p16, p21, Rb, cyclin A and cyclin E showed a stepwise increase from astrogliosis, through low- to high-grade astrocytomas, indicating the possibility that over 9%, 6% and 4% of LIs for p16, p21 and cyclin A, respectively, may be useful predictors in the case of the latter, in contrast to significant decrease in p27 LIs. Significantly higher mean LI values for cyclin D1 were also evident in astrogliosis (12.42) as compared with astrocytomas (low grade, 2.26; high grade, 4.60). Positive correlations between LIs for Rb and Ki-67 were observed with astrogliosis and low- but not high-grade tumours. In addition, high cyclin A LI values were independently associated with poor outcome in low-grade tumours. CONCLUSION: These findings provide evidence that expression of cell-cycle-related molecules may be a reliable parameter for differential diagnosis of low-grade astrocytomas and astrogliosis. Moreover, detection of cyclin A appears to be useful for predicting behaviour of low-grade astrocytomas.

Crosstalk between NF-kappaB/p65 and beta-catenin/TCF4/p300 signalling pathways through alterations in GSK-3beta expression during trans-differentiation of endometrial carcinoma cells.

Beta-catenin/TCF4/p300 signalling loops play an important role in trans-differentiation towards the morular phenotype of endometrial carcinomas. Crosstalk between NF-kappaB and beta-catenin pathways has been proposed and we focused here on associations between these two pathways during trans-differentiation. In normal endometrium, nuclear phosphorylated p65 (pp65), the active form NF-kappaB subunit, was found to be significantly increased in the secretory phase, correlating positively with vimentin and E-cadherin and inversely with Snail mRNA expression. On transfection of p65, vimentin, E-cadherin, and Snail were transcriptionally altered, indicating possible roles in establishment and maintenance of the secretory phenotype. In endometrial carcinomas with morules, levels of nuclear pp65, Snail mRNA, vimentin, and cytoplasmic TNF-alpha were reduced during trans-differentiation, correlating inversely with nuclear beta-catenin. Nuclear accumulation of GSK-3beta, along with beta-catenin, was observed in morules. In cell lines, overexpression of p65 inhibited beta-catenin/TCF4-mediated transcription, while transfection of GSK-3beta resulted in repression of TNF-alpha-induced NF-kappaB activity. Moreover, nuclear GSK-3beta was increased by overexpression of beta-catenin, as well as induction of G1-cell cycle arrest. These findings provide evidence that a shift from NF-kappaB to beta-catenin signalling pathways through alterations in GSK-3beta expression may be essential for the induction of trans-differentiation of endometrial carcinoma cells, leading to a shut-down of mesenchymal markers.

Intra-articular fracture of the knee with spondyloepiphyseal dysplasia congenita: successful result of open reduction and internal fixation.

In spondyloepiphyseal dysplasia congenita (SEDC), since the cartilage is congenitally abnormal, functional recovery of an intra-articular fracture is uncertain even with surgical treatment. We report a 29-year-old Japanese woman with SEDC whose left knee injury (intercondylar femur fracture and tibial plateau fracture) was surgically reduced and fixed. Although special care was required during the operation for associated atlantoaxial instability and cardiopulmonary suppression due to severe thoracolumbar kyphoscoliosis as well as osteopenia, she had neither restriction of knee motion nor pain at follow-up 2 years and 4 months after surgery. Therefore, although the situation involving fractures in a patient with SEDC is complicated, we believe the main problem to be solved is whether the risk-related kyphoscoliosis and atlantoaxial instability can be managed or not. Fractures themselves can be treated based on the principles used for patients without SEDC.

Age-dependent differences in tumor cell polarity in endometrial carcinomas.

PURPOSE: Cell polarization is dependent on the structural asymmetry of apical and basolateral domains. Although clinical and biological heterogeneity of endometrial carcinomas in aged individuals has been proposed, little is known about the age-dependent differences in tumor morphology in terms of cell polarity. To clarify a possible significance of tumor cell polarity, a total of 92 cases of grade (G) 1 and G2 endometrial carcinomas (endometrioid type) were investigated. METHODS: Cell polarity for tumor glandular components was evaluated by examining the degree of three morphological parameters: nuclear ordering, basal positioning of nuclei within cells, and papillary snouting/glandular convolution. The results were also compared with findings for cell proliferation, expression of p21(Cip1)(p21), p27(Kip1)(p27), estrogen and progesterone receptors, p53 accumulation, and several clinicopathological factors. RESULTS: Average values for each polarity parameter showed a stepwise decrease from tumors of pre-, through peri-, to post-menopausal patients, the difference being significant. Significantly high values for all polarity scores were also evident in tumors adjacent to secretory non-neoplastic endometrium as compared to those in non-secretory tissue. Positive correlations with low cell proliferation determined with respect to Ki-67 labeling indices, early clinical stage, and upper myometrial invasion were also noted, while there were no associations with expression of p21, p27, p53, and two hormone receptors. CONCLUSIONS: These findings indicate that in endometrial carcinomas, the age-dependent differences in tumor cell polarity may be related to status of endogenous ovarian hormones, closely linked with cell proliferation and some prognostic factors.

Loss of DCC expression in astrocytomas: relation to p53 abnormalities, cell kinetics, and survival.

AIMS: Although frequent reduction or loss of DCC (deleted in colorectal carcinomas) has been demonstrated in gliomas, the association with cell kinetics and survival is still unclear. METHODS: A total of 119 astrocytomas, comprising 39 grade IV, 36 grade III, and 44 low grade tumours, were immunohistochemically investigated, along with 26 normal adult brain samples and two fetal brains. The results were compared with p53 abnormalities, Ki-67 labelling index (LI), mitotic index (MI), apoptotic index (AI), and survival. RESULTS: In normal adult and fetal brain tissues, DCC expression was detected in mature and terminally differentiated neuronal cells but not glial elements. In astrocytomas, whereas DCC expression was still clearly shown with low grade malignancy, DCC scores were significantly decreased in high histological grade malignancy, along with an increase in cell kinetics determined by AI, MI, and Ki-67 LI values. In addition, p53 LI values were significantly increased, although a direct link between DCC scores and p53 LI values was not evident. Univariate analysis revealed that high DCC scores and low p53 LI values were closely related to a favourable outcome for astrocytoma, although only the AI was an independent prognostic factor. CONCLUSIONS: The loss of DCC expression may be closely related to changes in cell kinetics and tumour phenotype in astrocytomas, independent of p53 abnormalities.

Possible associations among expression of p14(ARF), p16(INK4a), p21(WAF1/CIP1), p27(KIP1), and p53 accumulation and the balance of apoptosis and cell proliferation in ovarian carcinomas.

BACKGROUND: Although there are several reports of changes in expression of cyclin-dependent kinase inhibitors in ovarian carcinomas, little is known about their associations with tissue kinetics in the various histologic subtypes. METHODS: In total, 131 carcinomas were immunohistochemically investigated for expression of p14(ARF) (p14), p16(INK4a) (p16), p21(WAF1/Cip1) (p21), and p27(Kip1) (p27). The results also were compared with data for apoptosis, cell proliferation, p53 status, and survival. Western blot and mRNA analyses were conducted on 35 malignant ovarian tumor samples. RESULTS: Significant differences in tissue kinetics determined by ratios of apoptotic relative to mitotic indices were observed among histologic subtypes of ovarian carcinomas, showing a shift toward predominance of cell proliferation in serous and cell deletion in clear cell types. The expression of p16, p21, p27, and p53 was associated closely with changes in cell proliferation rather than apoptosis and survival, dependent on the subtype. Positivity for p16 and p21 in the Western blot assay was significantly related to the results for immunohistochemical but not mRNA analyses, indicating possible posttranscriptional regulation of these genes. CONCLUSIONS: The findings indicate that the several cyclin-dependent kinase inhibitors investigated are expressed differently among histologic subtypes of ovarian carcinomas, associated with differences in tissue kinetics and the balance of apoptosis and cell proliferation.

Significant correlations of E-cadherin, catenin, and CD44 variant form expression with carcinoma cell differentiation and prognosis of extrahepatic bile duct carcinomas.

To clarify the relation between alteration of expression of cell adhesion molecules and progression of extrahepatic bile duct carcinomas. 55 cases were immunohistochemically examined for E-cadherin, alpha-catenin, beta-catenin, and CD44, with additional reverse transcription-polymerase chain reaction and Southern blotting hybridization (RT-PCR/SBH) assays. Levels of E-cadherin, alpha-catenin, and beta-catenin proteins were lower in carcinomas than in normal mucosa, while CD44 variants 3 and 6 were upregulated. Well-differentiated carcinoma showed higher expression of E-cadherin and alpha-catenin than moderately to poorly differentiated types. Macroscopically papillary lesions had higher expression of E-cadherin than their nonpapillary counterparts. RT-PCR/SBH for CD44 revealed the CD44 variant form to be more prevalent in carcinoma than in normal mucosa, correlating with the immunohistochemical results, and with more exon variety. The Cox proportional hazards test identified histologic type and E-cadherin expression as prognostic factors. Among the examined molecules, E-cadherin was especially related to papillary mass formation and a good prognosis.

[Septic shock due to pyonephrosis-calculosa: a case report].

A 69-year-old female was admitted to hospital with the complaint of high-grade fever and clouding of consciousness. Physical examination and laboratory data revealed septic shock, disseminated intravascular coagulation and multiple organ failure. Ultrasonography demonstrated left hydronephrosis and a cystic mass in peri-renal fatty tissue. KUB showed a left ureteral stone. A diagnosis of septic shock due to pyonephrosis-calculosa and peri-renal abscess was considered. A left nephrectomy, endotoxin removal therapy and continuous hemodiafiltration was performed. Thereafter all morbidities improved. A nephrectomy and intensive treatment are the good alternative method for such a case.

[Sexual function in men with lower urinary tract symptoms].

PURPOSE: Recently there have been several alternatives not only to improve symptoms but to retain an acceptable quality of life as well as to reduce the complications. Therefore the objective of this study was to evaluate quantitatively and qualitatively the degree of erectile dysfunction in the population of men with lower urinary tract symptoms (LUTS). MATERIALS AND METHODS: Total 252 men with LUTS were investigated using the International Prostate Symptom Score (I-PSS) and sexual function inventory (SFI) consisting of sexual drive, erection and ejaculation. Spearman's rank order correlation was used to determine the degree of any correlation between age, the total I-PSS, the individual I-PSS questions and the various sexual function scores. RESULTS: 208 patient data were available for analysis. There were poor function patients in 67.8% for sexual drive, in 46.2% for erection and in 47.1% for ejaculation. On the other hand, 24% considered their sexual drive to be a big or medium problem, 20.7% for erection and 18.3% for ejaculation. Overall, 27.4% of the men were mostly or very dissatisfied with their sex life. There was a significant correlation between a patient's age and his score for each of the three sexual variables (p < 0.05). Furthermore, a significant correlation was noticed between the total I-PSS and the SFI score (p < 0.05). It might be suggested that the more symptomatic a patient for LUTS, the poorer his sexual function will be. CONCLUSIONS: About 20% men with LUTS are bothered by their sexual symptoms. Erectile dysfunction in dependent of age and the extent of LUTS. Consideration of the high population of erectile dysfunction in men with LUTS is necessary to the treatment of their urinary symptoms.

Frequent nuclear beta-catenin accumulation and associated mutations in endometrioid-type endometrial and ovarian carcinomas with squamous differentiation.

Focal squamous differentiation is a common feature of endometrioid endometrial and ovarian carcinomas (E-Em and E-Ova Cas). A close association between mutated beta-catenin accumulation and alteration in cellular morphology has recently been demonstrated in murine L cell lines. To clarify the possible role of beta-catenin abnormalities and changes in tumour morphology, 60 grade (G) 1 or G2 E-Em Cas with areas of squamous differentiation (SqD), including morules and squamous metaplastic (SqM) foci, as well as 32 G1 or G2 tumours without such lesions, were investigated and the results compared with findings for c-jun and wnt-1 expression. Twenty-three E-Ova Cas, with and without SqD lesions, were also examined. In E-Em Cas, frequent nuclear beta-catenin accumulation was observed in 22 (84.6%) of 26 tumours with morules and 15 (45.5%) of 33 with SqM foci, in contrast to 4 (12.5%) of 32 without such lesions. Similar findings were also noted for mutations in exon 3 of the beta-catenin gene, involving codons 32, 33, 34, 37, 41, and 45, the single nucleotide substitutions being identical between SqD and the surrounding carcinoma tissue in most informative cases. The mutations were positively related to nuclear immunopositivity, but inversely to membrane expression, while there was no association with the status of c-jun or wnt-1. These E-Ova Cas, nuclear beta-catenin accumulation and mutations were limited to tumours with SqD features, independent of c-jun and wnt-1 status. These data indicate that beta-catenin abnormalities are relatively common in E-Em and E-Ova Cas with SqD features, implying a role in the squamous differentiation of tumour cells, not necessarily related to c-jun and/or wnt-1 status.

CD44 variant overexpression in gallbladder carcinoma associated with tumor dedifferentiation.

BACKGROUND: Recent studies have suggested a correlation between increased or decreased expression of CD44 variant molecules and tumor metastasis. CD44 expression in gallbladder carcinoma was examined and compared with tumor differentiation. METHODS: Eighty-three samples of gallbladder carcinoma, 17 gallbladder adenoma samples, and 66 normal control mucosa samples were stained immunohistochemically for CD44 standard form (CD44s), variant 3 (CD44v3), and variant 6 (CD44v6). RNA extracted from nine patients with carcinoma also was investigated with reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and Southern blot hybridization (SBH) for the CD44 gene. RESULTS: Normal gallbladder mucosa showed strong, membranous staining for CD44s but not for CD44v3 or CD44v6. In gallbladder tumors, CD44s was stained as strongly as it was in normal mucosa, but immunoreactivity for CD44v3 and CD44v6 also was significant. In well differentiated, advanced adenocarcinomas (n = 38), CD44s immunoreactivity was significantly lower in the invasive component than in the intramucosal component of the tumors (P = 0.0048). Immunoreactivity for CD44v3 and CD44v6 in moderately and poorly differentiated areas was significantly higher than in well differentiated areas (P < 0.0001 and P = 0.0378, respectively). RT-PCR and SBH signals for CD44v3 and CD44v6, including exons 7 and 10, were strong in carcinoma samples but weak in normal samples, in line with the results of immunohistochemistry. The prognosis of patients with gallbladder carcinoma was not associated significantly with altered expression of CD44s, CD44v3, or CD44v6. CONCLUSIONS: The current study demonstrated that CD44 variant overexpression in patients with gallbladder carcinoma was linked closely with histologic dedifferentiation rather than clinicopathologic factors, including prognosis.

More frequent beta-catenin exon 3 mutations in gallbladder adenomas than in carcinomas indicate different lineages.

To clarify the contribution of beta-catenin, which is related to cell adhesion and intranuclear transcription, to gallbladder carcinogenesis, we investigated its expression using immunohistochemistry, and beta-catenin exon 3 mutations by DNA direct sequencing, in 18 gallbladder adenomas and 82 adenocarcinomas. Membranous expression was significantly lower in moderately and poorly differentiated than in well-differentiated adenocarcinoma cases (P < 0.001). The gallbladder adenomas showed significantly stronger expression in the cytoplasm and the nucleus than carcinomas (P < 0.05 and P < 0.001, respectively), and exon 3 mutations were observed in 62.5% (10 of 16) of adenomas, but only 4.8% (1 of 21) of carcinomas. With beta-catenin as a molecular marker, the adenoma-carcinoma sequence can be considered to be a minor pathway in gallbladder carcinogenesis.

beta- Catenin mutations and aberrant nuclear expression during endometrial tumorigenesis.

To clarify the possible role of aberrant beta-catenin expression during endometrial tumorigenesis, a total of 199 cases of endometrial carcinomas (endometrioid type), as well as 37 cases of simple/complex and 32 of atypical hyperplasias, was consecutively investigated for immunohistochemistry, along with 141 normal endometrial samples distant from carcinomas. Of 199 carcinoma cases, 73 tumours as well as 44 normal samples were also analysed using a combination of RT-PCR and Southern blot hybridization, Western blot, and mutation gene assays. Cell membrane beta-catenin immunoreactivity showed a stepwise decrease from normal, through atypical hyperplasia, to grade 3 carcinomas. In contrast, the nuclear accumulation in atypical hyperplasias and grade 1 or 2 tumours was higher than in simple/complex hyperplasias. Mutations in exon 3 of the beta-catenin gene involving codons 33, 34, 37, 41, and 45 were observed in 16 (22.9%) of 70 endometrial carcinomas, as well as 3 (12.5%) of 24 atypical hyperplasias, the results being significantly related to low membrane and high nuclear immunoreactivity but not relative mRNA expression levels, suggesting that the gene mutations may be closely associated with changes in subcellular distribution. In addition to significant association between beta-catenin mutation and low grade histological malignancy (P = 0.048), the mutations were detected in none of 15 and 13 (26%) of 50 tumours with or without lymph node metastasis, the difference being significant (P = 0.027). These findings suggest that beta-catenin abnormalities may play an important role in a relatively early event during the endometrial hyperplasia-carcinoma sequence.

[Clinical evaluation of basic fetoprotein in bladder cancer].

PURPOSE: The early diagnosis of bladder cancer allows for effective local treatment and optimizes the success of surgical therapy. Basic fetoprotein (BFP), measured using a rapid latex immuno-agglutination method, was introduced for the detection of transitional cell carcinoma. The objective of this study was to determine whether there was a correlation between urine BFP level and the grade or stage of bladder cancer, and whether the level could serve as a biochemical marker of bladder cancer. MATERIALS AND METHODS: Single voided specimens were obtained from 66 patients with confirmed or suspicious bladder cancer on cystoscopy, urine cytology or BFP. Each sample was divided into 3 aliquots of which 1 was for urine analysis, 1 was tested for BFP according to latex immunoagglutination method and 1 was sent for cytological examination. All patients subsequently underwent bladder biopsy. RESULTS: There were 54 (82%) patients with biopsy confirmed bladder cancer and 12 (18%) with benign conditions of the bladder. Overall sensitivity with BFP and urine cytology was 38.9% and 48.1% respectively. Specificity was 58.3% and 75.0%, and positive predictive value was 80.8% and 89.7%, respectively. The positive rate of BFP and cytology was higher in invasive cancer (75% and 100%, respectively) than in superficial cancer (36% and 28%). There was no correlation between BFP level and tumor grade, while cytology had a strong association. Linear regression analysis showed the significant correlation between BFP level and tumor size (r = 0.695, p < 0.0001). The detection rate of bladder cancer was higher by the combination of BFP and cytology than by using alone. CONCLUSIONS: BFP in conjunction with urine cytology can increase the detection rate of bladder cancer. But BFP alone cannot be used as a screening test for bladder cancer.

Changes in expression of estrogen receptors alpha and beta in relation to progesterone receptor and pS2 status in normal and malignant endometrium.

To clarify changes in estrogen receptor (ER) alpha and ERbeta during endometrial tumorigenesis, 48 endometrial carcinomas (endometrioid type), as well as 40 samples of normal endometrial tissue, were investigated using a combination of reverse-transcription and polymerase chain reaction with Southern blot hybridization and western blot assays, and the results were compared with findings for progesterone receptor (PR) and pS2 mRNA status. In addition, 166 carcinomas were also examined for immunohistochemistry, along with 171 normal specimens. Relative amounts of ERalpha at both mRNA and protein levels were significantly greater than those for ERbeta in normal and malignant endometrial lesions. ERalpha mRNA showed a stepwise decrease from normal or grade (G) 1 through to G3 tumor lesions, in line with changes in the protein levels, in contrast to ERbeta mRNA or protein expression, which did not alter, suggesting a shift in the ratio of the two ER subtypes during endometrial tumorigenesis. PR mRNA expression was significantly correlated with ERalpha, but not ERbeta mRNA status. Although significantly higher expression of pS2 mRNA or protein was observed in carcinomas than in the normal cases, there was no apparent association with the ER status. The findings suggest that alteration in estrogen signaling pathways may occur during endometrial tumorigenesis, and provide evidence that ERalpha expression may play an important role in the regulation of PR, but not pS2 expression in normal and malignant endometrium.

Colonic mucin-carbohydrate components in colorectal tumors and their possible relationship to MUC2, p53 and DCC immunoreactivities.

To clarify changes in mucus components during colorectal tumorigenesis, we developed novel monoclonal antibodies (Abs) against carbohydrate chains of human colorectal mucin (HCM) obtained from normal sigmoid and rectal mucosae. A hundred and ninety-nine cases of colorectal carcinoma and 67 cases of tubular adenoma, along with 250 normal colonic tissue samples, were investigated immunohistochemically. The results were compared with clinical stage, survival and MUC2 (core protein of the intestinal type mucin) expression, as well as with the status of the p53 and DCC (deleted in colorectal carcinomas) genes. In the normal colonic epithelium, HCM14 Ab reacted with the cytoplasmic regions of the goblet cells and enterocytes, while HCM21 Ab bound to mucous droplets in the former, suggesting a more mature carbohydrate structure. Both HCM14 and 21 scores were significantly decreased in adenomas and carcinomas. This is in line with an altered PAS-Alcian blue staining, indicating accumulation of mucins with incomplete or abnormal glycosylation in tumors. Levels of HCM14 and 21 binding tended to show a positive correlation with expression of MUC2 and DCC, and a negative association with p53 protein accumulation in carcinomas, although there was no apparent link to Duke's stage or the prognostic outcome. These findings suggest a possible involvement of alterations in mucin carbohydrate in colorectal tumor development. The observed changes may be associated with loss of MUC2 and DCC expression, as well as with p53 protein accumulation.