Single nucleotide polymorphisms in the Gc gene for vitamin D binding protein in common cancers in Thailand.

BACKGROUND: This case-control study aimed to determine if there were any associations between the two single nucleotide polymorphisms (SNPs) in Gc, rs7041 (Asp416Glu) and rs4588 (Thr420Lys) and 3 common cancers (breast, lung and colorectal) in Thai patients. MATERIALS AND METHODS: Two hundred and eighty two colorectal, 101 breast and 113 lung cancer patients were recruited from one institute during 2011-2013. The controls were age-matched volunteers who had a negative history of index cancers. In addition, vitamin D levels were compared among different genotypes in the 2 SNPs. RESULTS: The minor allele frequencies of rs7041 (G) and rs4588 (A) were 0.32 and 0.24, respectively. Under the dominant model, the study found significant associations between minor-allele genotypes of the SNP rs7041 (TG/GG) and lung cancer (odds ratio [OR] 1.78, 95% CI 1.05-3.03). When subgroup analysis was performed according to sex and age at diagnosis, the study found that the minor- allele genotypes of rs7041 (TG/GG) were significantly associated with colorectal cancer in patients whose age at diagnosis was more than 60 years (OR 1.67, 95%CI 1.06-2.61) and the minor-allele genotypes of rs4588 (CA/AA) were significantly associated with colorectal cancer in males aged 60 years or less (OR 2.34, 95%CI 1.25-4.37). When SNP combinations (rs7041-rs4588) were examined, the TT-CA combination had a significant protective association with lung cancer (OR 0.44, 95% CI 0.22-0.85). On evaluation of serum 25(OH)D levels in 205 individuals without cancer (males 144, females 61), the proportion of subjects with low serum vitamin D (< 20 ng/ml) in those harboring CA or AA genotypes of rs4588 (41.7%) was significantly higher than the CC genotype (15.5%, p-value < 0.01). CONCLUSIONS: Genetic polymorphisms in Gc were associated with lung and colorectal cancers in Thai patients. Lower serum 25(OH)D in minor variants of rs4588 may explain this association.

HBV DNA level could predict significant liver fibrosis in HBeAg negative chronic hepatitis B patients with biopsy indication.

BACKGROUND: Non-invasive models and methods to substitute liver biopsy in chronic hepatitis B (CHB) patients were investigated but their roles as predictors of significant liver histology for diagnosis of HBeAg-negative CHB patients who had indication for liver biopsy according to The American Association for the Study of Liver Diseases (AASLD) and The Asian Pacific Association for the Study of the Liver (APASL) guidelines are still unknown. This study was designed to identify predictors of significant liver necroinflammation as defined by a Histology Activity Index of necroinflammatory score ≥ 4 or Metavir necroinflammatory activity score ≥ 2 and significant liver fibrosis as defined by a Metavir fibrosis score ≥ 2 in HBeAg-negative CHB patients that had a hepatitis B virus (HBV) DNA level ≥ 2,000 IU/ml and age ≥ 40 years or elevated alanine aminotransferase level between 1-2 times the upper limit of normal. METHODS: Twenty-two patients were prospectively included and performed liver biopsies. Clinical and laboratory parameters including age, gender, underlying disease, family history of cirrhosis or hepatocellular carcinoma, body mass index (BMI), HBV DNA level, HBsAg level, liver function test, complete blood count, aspartate aminotransferase-to-platelet ratio index and transient elastography were collected and analyzed with liver histology profiles. RESULTS: Five patients (23%) had significant liver inflammation and 7 patients (32%) had significant liver fibrosis. Factors associated with significant liver inflammation were a lower BMI and higher alkaline phosphatase level while a factor associated with significant liver fibrosis was lower age. On multivariate analysis, only HBV DNA level > 5.5 log IU/ml could predict significant liver fibrosis (odds ratio 28.012, 95% CI, 1.631-481.240, p = 0.022) and its sensitivity, specificity, positive predictive value and negative predictive value were 71.4%, 93.3%, 83.3% and 87.5% respectively. CONCLUSIONS: An HBV DNA level of > 5.5 log IU/ml was able to predict significant liver fibrosis for treatment of HBeAg-negative CHB patients that had indication for liver biopsy as recommended by AASLD and APASL guidelines.

Expression of BMP6 is associated with its methylation status in colorectal cancer tissue but lacks prognostic significance.

BACKGROUND: The study aimed to evaluate the incidence of CpG island promoter methylation of BMP6, a member of the transforming growth factor beta family, in tissue samples from colorectal cancers (CRC) and look for its association with BMP6 expression and clinicopathological correlation. MATERIALS AND METHODS: Methylation specific PCR for the BMP6 promoter region was performed with 85 frozen tissue samples of CRC and 45 of normal colon. Methylation status of MLH1 was also determined by the same method. Expression of BMP6 was evaluated by immunohistochemistry (IHC), using Allred's scoring system. The methylation status was analyzed against clinical and pathological parameters in CRC. RESULTS: The study revealed BMP6 hypermethylation in 34 of 85 tumor specimens (40%), and 15 out of 45 normal tissue samples from CRC (33%). The incidence of hypermethylation was inversely correlated with IHC score. Allred's scores of 7 or more were correlated with lower frequency of BMP6 hypermethylation (29% compared to 50% in the remaining, p-value 0.049). However, there was no association between hypermethylation status and any clinicopathological parameters. The methylation status of BMP6 was not correlated with that of MLH1, a key methylation determinant in CRC. On survival analysis, there was no significant difference in progress-free survival (PFS) between the cases with and without hypermethylation (2-year PFS 74% and 76%, respectively). CONCLUSIONS: CpG island methylation of BMP6 is found in high frequency in CRC and this epigenetic event is associated with suppressed protein expression in the tumor tissue. However, the marker is not associated with tumor progression of the disease.

1189 Gastrointestinal stromal tumor (GIST): computed tomographic features and correlation of CT findings with histologic grade.

OBJECTIVE: To characterize the CT features and to identify predictors of malignancy from CT of GISTs. MATERIAL AND METHOD: A retrospective review of CT images of 50 patients with pathologically and immunohistochemically proven GISTs was done by two radiologists and final interpretations were reached by consensus. Images were evaluated for site, size, contour boundary, growth pattern, enhancement pattern, degree of enhancement, necrosis, calcification, ulceration, perilesionalfat stranding, evidence ofbowel obstruction, and signs of malignancy. Categorical variables were compared using Fisher's exact test and continuous variables used the t-test. Univariate and multivariate logistic regression models were used to identify significant predictors ofa high mitotic rate. RESULTS: Of the 50 patients, the most common location of GISTs was stomach (62%) The mean size was 10.2 cm (SD 5.2 cm). The contour was lobulated in 84%. The boundary was smooth in 84%. The growth pattern was exophytic in 68%. Most of tumors had heterogeneous density on post-contrast images (88%). Necrosis (84%), calcification (14%), ulceration (40%), perilesionalfat stranding (44%), and bowel obstruction (2%) were present in the tumors. The CT signs of malignancy found were adjacent organ invasion (18%), ascites (18%), lymphadenopathy (6%), liver metastasis (20%), andperitoneal seeding (16%). Necrosis and peritoneal seeding were statistically significant independent predictors for high mitotic GISTs in multivariate logistic regression (p<0.05). The probability of a high mitotic rate was 1 (95% CI, 0.40-1.00) in the presence of both necrosis and peritoneal seeding. CONCLUSION: The stomach was the most common site of GIST The CT features of GIST were lobulated, smooth tumor margins, exophytic growth pattern, and heterogeneous enhancement on post-contrast CT images. Presence of both necrosis and peritoneal seeding were found to be a significant predictor of high mitotic rate of GISTs. The probability of a high mitotic rate was 1 (95% CI, 0.40-1.00).

Mutations of fibroblast growth factor receptor 3 gene (FGFR3) in transitional cell carcinoma of urinary bladder in Thai patients [Revision-2a].

OBJECTIVE: Determine the incidence of FGFR3 mutations in Thai patients with bladder transitional cell carcinoma (TCC), and evaluate their correlation with pathological characteristics. MATERIAL AND METHOD: One hundred twenty two frozen tissue samples from TCC patients were analyzed for mutations in exons 7, 10, and 15 of FGFR3 by polymerase chain reaction and direct DNA sequencing. RESULTS: FGFR3 mutations were detected in 22 of 122 cases (18%) studied, all of which were found within previously identified hotspots, including S249C (13 cases; 59%) and R248C (4 cases; 18%) in exon 7, and Y375C (5 cases; 23%) in exon 10, but no mutations in exon 15. Sixty-five patients (53%) were categorized as non-muscle-invasive TCC (pTa-pT1). The incidence of mutations is significantly higher in non-muscle-invasive tumors (28%) compared to the muscle-invading group (7%) (p < 0.01). Patients with grade (G) 1 TCC have significantly higher mutation frequency (40%) compared to other grades (4%) (p < 0.01). When T stage and grade were considered together, mutations were most commonly found in Ta-T1/G1 TCC (18/45 cases, 40%). Mean follow-up period was 45.1 months. Two-year and four-year overall survival (OS) was 70% and 56% respectively. Three-year OS in non-muscle-invasive TCC (80%) is significantly higher than that of muscle invading TCC (41%) (p < 0.01). However three-year OS in cases with an FGFR3 mutation (73%) is not significantly different from cases without a mutation (61%). In 16 cases with an FGFR3 mutation and recurrent disease, no mutations were detected in metachronous disease. CONCLUSION: The overall incidence of FGFR3 mutations in Thai patients with TCC was lower than similar reports from other ethnic groups. In the presented cases, although FGFR3 mutations were frequently detected in low-grade, non-muscle-invasive TCC, identical mutation was not conserved in metachronous disease, thereby precluding the use of this marker in detection of tumor recurrence.

NTRK3 is a potential tumor suppressor gene commonly inactivated by epigenetic mechanisms in colorectal cancer.

NTRK3 is a member of the neurotrophin receptor family and regulates cell survival. It appears to be a dependence receptor, and thus has the potential to act as an oncogene or as a tumor suppressor gene. NTRK3 is a receptor for NT-3 and when bound to NT-3 it induces cell survival, but when NT-3 free, it induces apoptosis. We identified aberrantly methylated NTRK3 in colorectal cancers through a genome-wide screen for hypermethylated genes. This discovery led us to assess whether NTRK3 could be a tumor suppressor gene in the colon. NTRK3 is methylated in 60% of colon adenomas and 67% of colon adenocarcinomas. NTRK3 methylation suppresses NTRK3 expression. Reconstitution of NTRK3 induces apoptosis in colorectal cancers, if NT-3 is absent. Furthermore, the loss of NTRK3 expression associates with neoplastic transformation in vitro and in vivo. We also found that a naturally occurring mutant NTRK3 found in human colorectal cancer inhibits the tumor suppressor activity of NTRK3. In summary, our findings suggest NTRK3 is a conditional tumor suppressor gene that is commonly inactivated in colorectal cancer by both epigenetic and genetic mechanisms whose function in the pathogenesis of colorectal cancer depends on the expression status of its ligand, NT-3.

Chalkley microvessel but not lymphatic vessel density correlates with axillary lymph node metastasis in primary breast cancers.

This study aimed to investigate tumor microvessel density (MVD) and lymphatic vessel density (LVD) using the Chalkley method as predictive markers for the risk of axillary lymph node metastasis and their relationship to other clinicopathological parameters in primary breast cancer cases. Forty two node-positive and eighty node-negative breast cancers were immunostained for CD34 and D2-40. MVD and LVD were counted by the Chalkley method at x400 magnification. There was a positive significant correlation of the MVD with the tumor size, coexisting ductal carcinoma in situ (DCIS) and lymph node metastases (P<0.05). In multivariate analysis, the MVD (2.86-4: OR 5.87 95%CI 1.05-32; >4: OR 20.03 95%CI 3.47-115.6), lymphovascular invasion (OR 3.46, 95% CI 1.13-10.6), and associated DCIS (OR 3.1, 95%CI 1.04-9.23) independently predicted axillary lymph node metastasis. There was no significant relationship between LVD and axillary lymph node metastasis. However, D2-40 was a good lymphatic vessel marker to enhance the detection of lymphatic invasion compared to H and E staining. In conclusion, MVD by the Chalkley method, lymphovascular invasion and associated DCIS can be additional predictive factors for axillary lymph node metastases in breast cancer. No relationship was identified between LVD and clinicopathological variables, including axillary lymph node metastasis.

Transforming growth factor-beta signaling promotes hepatocarcinogenesis induced by p53 loss.

UNLABELLED: Hepatocellular carcinoma (HCC) results from the accumulation of deregulated tumor suppressor genes and/or oncogenes in hepatocytes. Inactivation of TP53 and inhibition of transforming growth factor-beta (TGF-ß) signaling are among the most common molecular events in human liver cancers. Thus, we assessed whether inactivation of TGF-ß signaling, by deletion of the TGF-ß receptor, type II (Tgfbr2), cooperates with Trp53 loss to drive HCC formation. Albumin-cre transgenic mice were crossed with floxed Trp53 and/or floxed Tgfbr2 mice to generate mice lacking p53 and/or Tgfbr2 in the liver. Deletion of Trp53 alone (Trp53(KO) ) resulted in liver tumors in approximately 41% of mice by 10 months of age, whereas inactivation of Tgfbr2 alone (Tgfbr2(KO) ) did not induce liver tumors. Surprisingly, deletion of Tgfbr2 in the setting of p53 loss (Trp53(KO) ;Tgfbr2(KO) ) decreased the frequency of mice with liver tumors to around 17% and delayed the age of tumor onset. Interestingly, Trp53(KO) and Trp53(KO) ;Tgfbr2(KO) mice develop both HCC and cholangiocarcinomas, suggesting that loss of p53, independent of TGF-ß, may affect liver tumor formation through effects on a common liver stem cell population. Assessment of potential mechanisms through which TGF-ß signaling may promote liver tumor formation in the setting of p53 loss revealed a subset of Trp53(KO) tumors that express increased levels of alpha-fetoprotein. Furthermore, tumors from Trp53(KO) mice express increased TGF-ß1 levels compared with tumors from Trp53(KO) ;Tgfbr2(KO) mice. Increased phosphorylated Smad3 and ERK1/2 expression was also detected in the tumors from Trp53(KO) mice and correlated with increased expression of the TGF-ß responsive genes, Pai1 and Ctgf. CONCLUSION: TGF-ß signaling paradoxically promotes the formation of liver tumors that arise in the setting of p53 inactivation.

Clinical outcomes of gastrointestinal stromal tumor in southern Thailand.

AIM: To review a single institutional experience in clinical management of gastrointestinal stromal tumors (GIST) and analyze for factors determining treatment outcome. METHODS: Clinicopathological data of patients with a diagnosis of GIST who were treated at our institute during November 2004 to September 2009 were retrospectively reviewed. RESULTS: Ninety-nine cases were included in the analysis. Primary tumor sites were at the stomach in and small bowel in 44% and 33%, respectively. Thirty-one cases already had metastasis at presentation and the most common metastatic site was the liver. Sixty-four cases (65%) were in the high-risk category. Surgical treatment was performed in 77 cases (78%), 3 of whom received upfront targeted therapy. Complete resection was achieved in 56 cases (73% of operative cases) and of whom 27 developed local recurrence or distant metastasis at a median duration of 2 years. Imatinib was given as a primary therapy in unresectable cases (25 cases) and as an adjuvant in cases with residual tumor (21 cases). Targeted therapy gave partial response in 7 cases (15%), stable disease in 27 cases (57%) and progressive disease in 13 cases (28%). Four-year overall survival was 74% (95% CI: 61%-83%). Univariate survival analysis found that low-risk tumor, gastric site, complete resection and response to imatinib were associated with better survival. CONCLUSION: The overall outcomes of GIST can be predicted by risk-categorization. Surgery alone may not be a curative treatment for GIST. Response to targeted therapy is a crucial survival determinant in these patients.

Peripheral precocious puberty in a male caused by Leydig cell adenoma harboring a somatic mutation of the LHR gene: report of a case.

While a germline activating mutation of the luteinizing hormone receptor (LHR) gene is known to cause autonomous production of testosterone from testicular Leydig cells in male-limited precocious puberty, only a few studies have addressed the role of somatic LHR mutation in testicular pathology. The authors report a case of a 6-year-old boy who developed secondary sex characteristics including facial acne, enlarging genitalia, and aggressive behavior, for which serial biochemical evaluation confirmed the status of peripheral precocious puberty. Examination revealed asymmetrical testicular volume, following which a left testicular tumor was detected through ultrasonography. A left orchiectomy was performed, and histopathology revealed a well-circumscribed Leydig cell tumor Molecular study of the exon 11 of the LHR gene revealed a missense mutation at the nucleotide position 1,732, leading to a substitution of histidine for aspartic acid at codon 578. Interestingly, the substitution was consistent with all previously reported LHR alteration in pediatric Leydig cell adenoma, but which had never before been reported in male-limited precocious puberty, suggesting that the mutation is a molecular signature of the adenoma.

The significance of galectin-3 immunohistochemistry, clinical characteristics and liver imaging in differentiating intrahepatic cholangiocarcinoma from adenocarcinoma liver metastasis.

OBJECTIVE: To identify differences of Galectin-3 (Gal-3) immunostaining, clinical profiles, and images in patients with intrahepatic cholangiocarcinoma (IHC) and adenocarcinoma liver metastasis, and be able to recognize these parameters as diagnostic tools for differentiating these two diseases. MATERIAL AND METHOD: Histological slides from patients with IHC and adenocarcinoma liver metastasis were reviewed Immunohistochemical staining for Gal-3, Cytokeratin-7 (CK-7), and Cytokeratin-20 (CK-20) was performed and the results categorized. Moreover clinical characteristics and liver images of the patients were reviewed. RESULTS: Eighty-two patients were evaluated, 31 IHC and 51 adenocarcinoma liver metastasis. Patients who strongly expressed Gal-3 were positive for CK-7 and negative for CK-20. Finding showed that 86% of them were IHC whereas only 14% were in adenocarcinoma liver metastasis. All patients with liver images showing a single lesion, located at central site, and having intrahepatic duct dilatation were IHC. On the other hand, 77% of patients with liver imaging showing multiple liver masses, located at peripheral site and having no intrahepatic duct dilatation were adenocarcinoma liver metastasis while only 23% were in IHC. CONCLUSION: Adding Gal-3 to CK-7 and CK-20 immunohistochemistry has benefits to differentiate IHC from adenocarcinoma liver metastasis. Furthermore, liver imaging profiles also give benefits for differentiating between these two diseases.

Wilms' tumor 1 gene (WT1) is overexpressed and provides an oncogenic function in pediatric nephroblastomas harboring the wild-type WT1.

Wilms' tumor 1 gene (WT1) is known to be a tumor suppressor gene in the subset of nephroblastomas that harbors WT1 mutations. However, its role in nephroblastomas without mutations remains unclear. This study aimed to evaluate the expression of WT1 and its potential oncogenic role in pediatric nephroblastoma with wild-type WT1. A total of 24 nephroblastomas were studied for WT1 mRNA expression by quantitative reverse-transcription polymerase chain reaction. The expression levels were compared between nephro-blastomas with and without WT1 mutations, as well as to normal kidney tissue, other pediatric renal tumors and neuroblastomas. Immunohistochemistry was used to evaluate expression patterns at the tissue level. Post-transcriptional inhibition of WT1 was performed in primary cultures of wild-type nephroblastoma using WT1 siRNA. The average WT1 expression level in nephroblastoma tissue was significantly higher than that in normal kidney tissue and neuroblastomas. Expression at the mRNA level was not different between nephroblastomas with WT1 mutations (4 cases) and those with wild-type WT1 (20 cases). However, while WT1 immunoreactivity was positive in all of the nephroblastoma components in the tumors with wild-type WT1, the protein expression was weaker and limited to stromal components in the tumors with mutated WT1, where it co-localized with ß-catenin nuclear accumulation. The post-transcriptional inhibition of WT1 resulted in growth retardation and a significantly increased apoptotic fraction. Our study found overexpression of the WT1 gene in pediatric nephroblastomas with wild-type WT1. Moreover, the study suggests an oncogenic role of WT1 in this tumor subset.

Cushing's syndrome in an infant secondary to malignant adrenocortical tumors with somatic mutation of beta-catenin.

A role of beta-catenin (CTNNB1) in the molecular pathogenesis of adrenocortical carcinoma (ACC) has been suspected in adult ACC and pediatric pigmented nodular adrenocortical disease, but it has never been reported in pediatric ACC. We present the case of a 4-month-old Thai infant who had Cushing's syndrome secondary to bilateral adrenal tumors with hepatic metastasis. The child was successfully treated with a bilateral adrenalectomy and wedge resection of the liver nodule. Histopathology revealed bilateral adrenocortical tumors with different histologic grades; the right tumor had a higher score, according to modified Weiss criteria. On molecular study, a deletion mutation of beta-catenin involving codons 44 to 45 was detected in the right adrenal tumor. The same mutation was found in peripheral blood before treatment; this mutation disappeared after tumor removal. The left tumor harbored wild-type beta-catenin. Immunohistochemistry showed nuclear accumulation of beta-catenin on the right adrenal tumor and the metastatic nodule. In summary, we present evidence that supports the role of the Wnt-signaling pathway in the carcinogenesis of pediatric adrenocortical carcinoma.

Immunohistological evidence for Wnt-signaling activation in Peutz-Jeghers polyposis.

OBJECTIVE: Molecular pathogenesis of gastrointestinal polyposis in Peutz-Jegher's syndrome (PJS) has been linked to the loss-of-function mutation of LKB1. Recent functional genetic studies have pointed out that LKB1 plays a physiological role in controlling the Wnt-signaling pathway and activation of the pathway as a consequence of LKB1 haploinsufficiency might be responsible for the development of harmatomatous polyps. This study aimed to look for immunohistochemical evidence of Wnt-signaling activation in PJS polyps. METHOD: Beta-catenin immunohistochemistry patterns were evaluated in gastrointestinal polyps from five cases of PJS. All patients were also evaluated for germline mutations of LKB1 and somatic mutations of beta-catenin in the polyps. RESULTS: Four of the five cases had germline mutations of LKB1, including two novel mutations, a one-base insertion at codon 53 and a large deletion encompassing exon 3 (codon 136-155). PJS polyps from all patients showed generalized membrane and cytoplasmic localizations of beta-catenin along the mucosal endothelium. Polyps from two cases with LKB1 mutations revealed moderate-intensity nuclear staining in approximately 20 and 70% of the polyps. CONCLUSION: The study offers additional evidence of Wnt-signaling activation in PJS polyp development at the tissue level, although the degree of up-regulation was not as high as has been found in Wnt-associated neoplasms.

Comparability of different pathologic protocols in sentinel lymph node evaluation: an analysis of two step-sectioning methods for the same patients with breast cancer.

CONTEXT: The pathologic protocol for sentinel lymph node evaluation has yet to be standardized. Results from previous studies are troublesome to compare because they have been conducted on different sets of subjects with cancer. OBJECTIVE: To compare the detection of sentinel lymph node metastases by using step-sectioning methods at 20-microm and 150-microm intervals for the same patient with primary breast cancer. DESIGN: A total of 186, initially tumor-negative sentinel lymph nodes from a group of 80 patients with breast cancer were included. For all nodes, each paraffin block was cut serially to produce a total of 10 levels: 5 consecutive levels of sections for each of the 20-microm and 150-microm intervals. The nodal findings obtained at these intervals on hematoxylin-eosin and cytokeratin slides were compared by using the McNemar test. RESULTS: The overall detection rate for sentinel lymph node metastasis at intervals of 20 microm and 150 microm was 27.5% (22/80) and 20% (16/80), respectively. The overall agreement between the 20-microm and 150-microm sections was 82.5%. No macrometastasis was missed by either method. At the 20-microm interval, 2 cases of micrometastasis were missed, while 10 cases of isolated tumor cells were missed at the 150-microm interval. However, no statistical difference was observed for the final sentinel lymph node results with either method. (McNemar test, P = .18 for case-based results and P = .052 for nodal-based results). CONCLUSIONS: The 20-microm and 150-microm interval step-sectioning methods produce comparable results for detection of metastatic deposits in sentinel lymph nodes.

Overall expression of beta-catenin outperforms its nuclear accumulation in predicting outcomes of colorectal cancers.

AIM: To examine the expression of beta-catenin in colorectal cancer and look for association with other clinico-pathological parameters. METHODS: Tumor samples from 163 cases of colorectal cancer (CRC) who had undergone primary colectomy between May, 1998 and November, 2002 with complete follow-up data for either 5 years or until death were recruited for a beta-catenin immunohistochemical study. The percentage of immunoreacted tumor cells was defined as overall staining density (OSD) and percentage of cells having nuclear localization was counted as nuclear staining density (NSD). Univariate exploration used log-rank test and multivariate survival analysis used Cox's hazard regression model. RESULTS: Beta-catenin immunoreactivity was detected in 161 samples (98.8%), of which 131 cases had nuclear staining. High OSD (> or = 75%), detected in 123 cases (75.5%), was significantly associated with earlier clinical staging (P < 0.01), lower nodal status (P = 0.02), non-metastatic status (P < 0.01) and better differentiation (P = 0.02). Multivariate analysis found that high OSD was independently associated with better survival [Cox's hazard ratio 0.51, 95% confidence interval (CI) 0.31-0.83]. Although high NSD (> or = 75%) was correlated with high pre-operative serum CEA (P = 0.03), well differentiation (P < 0.01), and increased staining intensity (P < 0.01), the parameter was not significantly associated with survival. CONCLUSION: Unlike previous reports, the study did not find a predictive value of nuclear beta-catenin in CRC. Instead, the overall expression of beta-catenin in CRC showed an association with better differentiation and earlier staging. Moreover, the parameter also independently predicted superior survival.

Prenatal diagnosis of complete trisomy 9: a case report and review of the literature.

Complete trisomy 9 is a very rare chromosome aneuploidy, associated with specific patterns of multisystem dysmorphism and a wide spectrum of congenital anomalies. We present a case of complete trisomy 9 with prenatal sonographic findings in the second trimester. The combination of sonography and karyotyping from cordocentesis enabled us to establish the prenatal diagnosis. An additional clinical feature of this syndrome that has not been reported previously is an aortopulmonary communication. A review of the literature specifically dealing with prenatal sonographic findings with complete trisomy 9 is also presented.

Primary peritoneal adenosarcoma with stromal overgrowth and fetal type cartilage: a case report and literature review.

Primary peritoneal adenosarcoma with sarcomatous overgrowth and fetal-type cartilage presented in a 48-year-old female patient is described. The tumor seems likely to have derived from the pelvic peritoneum, wheareas the uterus, ovaries and tubes were uninvolved. It was composed of benign-appearing glands and a sarcomatous component showing cartilaginous differentiation. The extrauterine adenosarcomas were reported in other sites, e.g. cervix, ovary, fallopian tube, bladder, and peritoneum. This case was the ninth case of the primary peritoneal adenosarcoma in the English literature and the first report in Thailand.

Anorectal malignant melanoma: report of two cases from Buddhachinnaraj Hospital.

Anorectal malignant melanoma is a rare disease and has a uniformly poor prognosis. The following are two reported cases from Buddhachinaraj Hospital. A 55-year-old and a 65-year-old female patients presented with rectal bleeding. Large anorectal masses with regional lymph node involvement were detected initially. They exhibited different histological features which were atypical round cell resembling lymphocytes or were small cell appearance and spindle cell appearance similar to sarcoma. The diagnosis was confirmed by expression of S100 protein and HMB45. Abdominoperineal resection (APR) was the treatment of choice in both patients. The former case died in the fourth month after diagnosis because of distance metastasis and congestive heart failure. The latter case is receiving postoperative adjuvant therapy.