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Background The von Hippel-Lindau (VHL) tumor suppressor gene located on chromosome 3p25-26 is implicated in VHL disease. Two informative single nucleotide polymorphisms are at positions 19 and 1149 on the nucleotide sequence from Gene Bank NM_000551 . In this study we examined the allele frequencies at these two loci in the Taiwanese population and compared the results to those from European ethnic populations. Methods The allele frequency was examined in 616 healthy individuals including 301 university students and 315 neonates. Both A/G polymorphisms were investigated using restriction fragment length polymorphism analysis created by restriction enzymes, BsaJ I and Acc I. Results Among these subjects, the allele frequencies at 19 SNP and 1149 SNP for variant G were 0.130 and 0.133, respectively. And these results were significant differences from those of the Caucasian populations. In addition, 90% of the tested subjects had identical genotypes at these two loci suggesting the existence of nonrandom association of alleles. Conclusion We found that the G allele frequency at these two loci in the Taiwanese population is much lower than that in people from Western countries. This phenomenon may be attributed to ethnic effects.

Our purpose was to investigate the histopathologic changes in uterine leiomyomas in cell proliferation, proliferating cell nuclear antigen expression, angiogenesis, and apoptosis after treatment with gonadotropin-releasing hormone agonist.Fifteen consecutive patients who had undergone gonadotropin-releasing hormone agonist treatment before surgery and 44 patients who did not were studied. The volumes of myomas were determined ultrasonographically, and in patients receiving gonadotropin-releasing hormone agonist therapy measurements were done again after administration of the gonadotropin-releasing hormone agonist to evaluate the response to treatment. Paraffin sections were stained with hematoxylin and eosin, PC 10 for proliferating cell nuclear antigen expression, MIB 1 for measurement of cell proliferation, ApopTag for apoptosis, and factor VIII for quantitation of microvessel density. A deoxyribonucleic acid fragmentation test was also done on nine cases with available frozen tissues.Most of the leiomyomas showed substantial expression of proliferating cell nuclear antigen. Gonadotropin-releasing hormone agonist therapy further induced significant overexpression of proliferating cell nuclear antigen (p = 0.0004, chi 2 test). All three leiomyomas that failed to respond to therapy showed less proliferating cell nuclear antigen staining compared with the good responders. In contrast, data from MIB 1 immunostaining showed that0.3% of leiomyoma cells were proliferating. However, positive-staining cells were more frequently detected in the treatment group (0.075% +/- 0.091% vs 0.002% +/- 0.010%, p = 0.0002, Mann-Whitney U test). Apoptosis developed spontaneously in leiomyoma cells independent of gonadotropin-releasing hormone agonist therapy. No significant change in apoptosis but a significant increase in microvessel density was observed in the treatment group compared with the control group.Enhanced deoxyribonucleic acid damage or repair with cell growth arrest may be responsible for the action of gonadotropin-releasing hormone agonist in shrinking uterine leiomyomas. Moreover, the extent of proliferating cell nuclear antigen expression seems to be associated with the response to gonadotropin-releasing hormone agonist therapy.

To investigate the differences of biological aggressiveness in terms of proliferating cell nuclear antigen (PCNA) expression, cell proliferation, and microvessel density between uterine leiomyosarcoma and leiomyoma.All patients with uterine leiomyosarcoma undergoing surgery at National Cheng Kung University Hospital were eligible. Forty-four patients with uterine myoma were also studied as the benign counterpart. The paraffin-embedded slides were stained with hematoxylin and eosin to confirm the presence of tumor and to quantitate mitoses, PC 10 for measurement of PCNA expression, MIB 1 for measurement of cell proliferation, and factor VIII for quantitation of microvessel density. The immunohistochemical findings of the slides were correlated with clinocopathologic findings of the patients, and the data were analyzed by either chi2 or unpaired t test.Six patients with uterine leiomyosarcoma and 44 patients with uterine leiomyoma were studied. Statistically significant higher mean levels of PCNA and MIB 1 were observed in uterine leiomyosarcoma compared with those of uterine myoma (for PCNA expression, P = 0.0001; for MIB 1, 11.61 +/- 11.42% vs 0.45 +/- 0.21%, P0.0001). No significant difference of microvessel density was observed between these two groups (65.73 +/- 48.62 vs 41.97 +/- 28.20, P = 0.084). Among the six patients with leiomyosarcoma, two patients with a higher percentage of MIB 1-positive tumor cells died of recurrent disease. In contrast, two patients with lower MIB 1 counts were disease-free for 3 years or more.Deregulated cell growth in uterine leiomyosarcoma may account for the biological aggressiveness of this tumor. Furthermore, the percentage of MIB 1-positive tumor cells seems to be associated with the prognosis or extent of uterine leiomyosarcoma.

Objective To investigate the correlation of intratumoral blood flow in uterine myoma with cell proliferation, angiogenesis, tumor size, and tumor volume. Methods Thirty-nine patients who had been scheduled for surgery because of symptomatic uterine myomas were evaluated by transvaginal sonography and color Doppler ultrasound before surgery. The largest dimension of each tumor and the volumes of myomas were determined ultrasonographically. Pulsatility index (PI) was determined by color Doppler ultrasound according to the maximum systolic, end-diastolic, and the mean flow velocities measured within the uterine nodules. After surgery, the paraffinembedded slides containing representative leiomyoma tissues were stained with hematoxylin and eosin, proliferating cell nuclear antigen for measurement of cell proliferation, and factor VIII for quantitation of microvessel density. The ultrasonographic findings were correlated postoperatively with pathologic findings, and the data were analyzed by simple linear regression and Fisher r to z transformation. Results Simple regression analysis of the intratumoral PI values on the sizes of myomas showed a negative correlation ( r = −0.47, P = .003; n = 39), whereas a less significant correlation between PI values and tumor volumes was observed ( r = −0.42, P = .008). In contrast, no statistically significant correlation was observed between the intratumoral PI values and the values of the proliferating cell nuclear antigen index ( r = 0.10, P = .547) or microvessel density counts ( r = 0.18, P = .282). Conclusion The intratumoral blood flow by transvaginal color Doppler ultrasound correlated with a reduced tumor size and tumor volume, but did not correlate with cell proliferation or angiogenesis.

Hepatic angiosarcoma (HAS) is a rare primary mesenchymal malignancy of liver with close association to arsenic intoxication. Although the southwest coastal area of Taiwan is well known for its prevalence of arsenic intoxication from drinking well water, few cases of HAS associated with arsenic ingestion have been reported. We report a case of HAS complicated by spontaneous hepatic rupture in a 68-year-old female farmer who presented with acute onset of abdominal pain and shock. The arsenic level in her drinking water had been found to be 0.12 ppm at her childhood home and 0.005 ppm at her residence from age 21 to 68 years. The total ingested arsenic was estimated to be 1.9 g, and the latent period was about 25 years with a weighted mean exposure of 0.12 mg/day. We also reviewed data collected by the National Cancer Registry Program from 1981 to 1999 and identified 25 additional reported cases. The median age of these patients was 55 years, and the male-to-female ratio was 1.9 (17:9). Whereas no case was found during this period in the blackfoot disease (BFD) endemic area, a hyperendemic area of arsenic intoxication in Taiwan, this case demonstrates the existence of cases of HAS associated with exposure to high levels of arsenic near the BFD area in Taiwan.

The detection is described of hepatitis B virus (HBV)-DNA in preserved hepatocellular carcinoma tissues, which were derived from 14 HBV-seropositive patients. Detection was by polymerase chain reaction (PCR) amplification of the target sequence, followed by specific localization of the PCR product with in situ hybridization. PISH (PCR-in situ hybridization) yielded strong positive signals in most of the tumor tissues despite very low copy numbers of chromosome-integrated HBV genome, whereas no signal was detected in control samples, indicating that the signals were specific for HBV. Positive signals were sometimes detected in cirrhotic nodules surrounding the tumor regions, indicating that HBV had infected non-transformed liver cells. HBV-DNA was detected in both nucleus and cytoplasm in some specimens, possibly representing HBV at different stages of the life cycle. In one case, a gradient of viral DNA was revealed, with the highest DNA signal centered at the site of viral antigen expression. Taken together, PISH is shown to be a highly sensitive molecular detection method that is capable of detecting the presence of a low copy number viral genome in situ.