Downregulation of nuclear and cytoplasmic Chibby is associated with advanced cervical cancer.

Chibby has been identified as a putative tumor suppressor and antagonist to ß-catenin, thereby controlling the Wnt signaling pathway. Chibby is typically downregulated in numerous types of cancer and may be associated with tumorigenesis. The present study aimed at clarifying the following: i) Whether Chibby antagonizes ß-catenin in cervical cancer; ii) whether Chibby and ß-catenin mRNA expression is associated with cancer progression; and iii) whether Chibby and ß-catenin expression may be used as a biomarker. A total of 87 paraffin-embedded cervical sections with distinct cervical intraepithelial neoplasia (CIN) stages (chronic cervicitis, CIN 1, CIN 2, CIN 3 and invasive squamous cell carcinoma) were collected between June 2004 and October 2012 The mRNA expression level of Chibby and ß-catenin was determined using the polymerase chain reaction. Protein expression and cellular localization of Chibby and ß-catenin were determined using immunohistochemistry. Chibby and ß-catenin were analyzed for possible association with the progression of cervical cancer. Chibby mRNA expression and the Chibby/ß-catenin ratio were identified to be downregulated in invasive tumors. Positive cytoplasmic and nuclear staining for Chibby was associated with CIN staging and decreased as the CIN stage increased. In addition, the cytoplasmic and membrane intensity of ß-catenin was associated with invasive tumors, in which a significantly increased level of protein expression was detected. Chibby may be a tumor suppressor in cervical cancer, since the dysregulation of Chibby expression is associated with tumorigenesis in cervical cancer. Chibby and ß-catenin expression together may potentially to a biomarker for disease progression in cervical cancer.

Differential roles of Bcl2L12 and its short variant in breast cancer lymph node metastasis.

Bcl2L12 plays a role in post-mitochondrial apoptosis through multiple mechanisms involving p53, αB-crystallin, caspase-3 and -7 in glioblastoma. Bcl2L12 is reported to be a good prognostic marker in breast cancer and correlated with ER and Bcl2 expression status. However, the mechanisms by which Bcl2L12 regulates apoptosis in breast cancer (BCa) remain unknown. Recent studies have shown that Bcl2L12 expression is a useful biomarker in other types of cancer. Thus, we examined whether Bcl2L12 and Bcl2L12A mRNA were associated with breast cancer progression or a specific subtype. In total, 106 paraffin-embedded, different stage breast cancer specimens were prepared and quantified for Bcl2L12 and Bcl2L12A expression by PCR. The correlation between Bcl2L12 and Bcl2L12A mRNA levels and clinicopathological characteristics was statistically analyzed. The results showed that Bcl2L12 and Bcl2L12A mRNA expression was not significantly different across the different stage, grade and TNM classification groups (P>0.005). Using linear regression, Bcl2L12 mRNA was associated with Bcl2L12A mRNA, grade 3 tumor and the triple-negative breast cancer (TNBC) subtype. In non-TNBC specimens, Bcl2L12 mRNA was only correlated with Bcl2L12A mRNA. Bcl2L12A mRNA was positively associated with Bcl2L12 mRNA and the number of lymph node metastases, but negatively correlated with staging in the non-TNBC group. Specifically, Bcl2L12, but not Bcl2L12A, mRNA was significantly higher in TNBC and grade 3 tumors, respectively. In non-TNBC, Bcl2L12A mRNA was significantly highly expressed in tumors with ≥ 12 metastatic lymph nodes. Bcl2L12 and its variant mRNA were highly expressed in carcinoma in situ (CIS) samples. In addition, they were estimated to be correlated with the total sample and non-TNBC, but not the TNBC group. In summary, a high Bcl2L12 mRNA expression was associated with the high-grade BCa and TNBC subtype. In addition, the interplay between Bcl2L12 and its variant may be associated with high lymph node metastasis in non-TNBC tumors.

p53 codon 72 polymorphism and susceptibility malignancy of colorectal cancer in Taiwan.

PURPOSE: The p53 tumor suppressor gene plays two important roles in genomic stability: blocking cell proliferation after DNA damage until it has been repaired, and starting apoptosis if the damage is too critical. A recent report suggests that a polymorphism of the p53 tumor suppressor gene that results in the substitution of a proline residue with an arginine residue at position 72 of the p53 protein might act as a risk factor in the malignant transformation of colorectal adenoma to cancer. METHODS: In our study, the samples consisted of 150 patients were analyzed for the mutation in the p53 gene. The age of 150 patients (46 women and 104 men) ranged from 30 to 91 years (mean age 68.46 years). RESULTS: The polymorphism showed 52.04% mutant in the codon 72 of exon 4 in the Taiwanese population. Both of the chi-square for trend test (chi-square = 4.97, p = 0.034) and logistic regression (p = 0.037, odds ratio = 1.699) showed significant differences in the distribution of polymorphism of codon 72 in the p53 gene and Dukes classification of colorectal cancer. CONCLUSIONS: There were significant relationship between the polymorphism of codon 72 and the malignancy of colorectal cancer in Taiwanese population. There is 1.70 times in each grade change (Dukes A-D) more risk of CCC polymorphism than that of CCG polymorphism of codon 72 of exon 4.

Glomus tumor of the trachea.

Glomus tumor of the trachea is extremely rare. There were approximately 15 reported cases before. Herein, we report another case of glomus tumor of the trachea in a 50-year-old woman presenting with cough and dyspnea for 8 years. She suffered from hemoptysis for 1 day before this admission. Bronchoscopy and CT scan showed a polypoid tumor protruding into the tracheal lumen and with extraluminal extension. The tumor was located at 9 cm below the vocal cord and 1.5 cm above the carina. It measured 2.5 x 2.5 x 2.0 cm and arose from the posterior wall of the trachea. Microscopically, the tumor consisted of a sheet of uniform cells surrounding the vascular spaces. Only few scattered tumor cells showed weak positive staining for muscle actin (HHF-35) by immunohistochemical stain. Ultrastructural study confirmed the presence of small amount of myofibrillar bundles with focal densities in some of the tumor cells. Other cells exhibited only rare or very sparse myofilaments. Characteristic feature of fine pinocytotic vesicles along the plasma membrance of the tumor cells was also noted.

Mutations in the p53 tumor suppressor gene in colorectal cancer in Taiwan.

Mutations in the tumor suppressor gene p53 have been reported as occurring prevalently in a wide range of human tumors. Detection of a mutated p53 is thought to provide useful information for the clinical management of colorectal neoplasm. In this study, we used polymerase chain reaction/single-strand conformation polymorphism (PCR/SSCP) and sequencing analysis to rapidly screen for mutations in p53 in colorectal cancer in Taiwan. Genomic DNA was purified from colorectal cancer specimens obtained from 80 patients at a teaching hospital in southern Taiwan. Primer sets were designed to amplify fragments within exons 4-8 of p53. We found p53 mutations in 38 of 80 patients. This is the first identification of a mutation at codon 143 of p53 in colorectal cancer in Taiwan. In addition, we found two insertions in exon 5 of p53. The p53 mutation rate among colorectal tumors in Taiwan, found in this study, is 43%. The results indicate that p53 mutation is not significantly associated with tumor grade, age, or gender (p > 0.05). We found that two-fifths of colorectal cancer patients in Taiwan have a p53 mutation, which could be used as a marker of colorectal cancer.