Heterozygous/dispermic complete mole confers a significantly higher risk for post-molar gestational trophoblastic disease.

Hydatidiform moles are classified at the genetic level as androgenetic complete mole and diandric-monogynic partial mole. Conflicting data exist whether heterozygous complete moles are more aggressive clinically than homozygous complete moles. We investigated clinical outcome in a large cohort of hydatidiform moles in Chinese patients with an emphasis on genotypical correlation with post-molar gestational trophoblastic disease. Consecutive products of conceptions undergoing DNA genotyping and p57 immunohistochemistry to rule out molar gestations were included from a 5-year period at Beijing Obstetrics and Gynecology Hospital. Patient demographics and clinical follow-up information were obtained. Post-molar gestational trophoblastic disease or gestational trophoblastic neoplasia was determined by the 2002 WHO/FIGO criteria. A total of 1245 products of conceptions were classified based on genotyping results into 219 complete moles, 250 partial moles, and 776 non-molar gestations. Among 219 complete moles, 186 were homozygous/monospermic and 33 were heterozygous/dispermic. Among 250 partial moles, 246 were triploid dispermic, 2 were triploid monospermic, and 2 were tetraploid heterozygous partial moles. Among 776 non-molar gestations, 644 were diploid without chromosomal aneuploidies detectable by STR genotyping and 132 had various genetic abnormalities including 122 cases of various trisomies, 2 triploid digynic-monoandric non-molar gestations, 7 cases of possible chromosomal monosomy or uniparental disomy. Successful follow-up was achieved in 165 complete moles: post-molar gestational trophoblastic disease developed in 11.6% (16/138 cases) of homozygous complete moles and 37.0% (10/27 cases) of heterozygous complete moles. The difference between the two groups was highly significant (p = 0.0009, chi-square). None of the 218 partial moles and 367 non-molar gestations developed post-molar gestational trophoblastic disease. In conclusion, heterozygous/dispermic complete moles are clinically more aggressive with a significantly higher risk for development of post-molar gestational trophoblastic disease compared with homozygous/monospermic complete moles. Therefore, precise genotyping classification of complete moles is important for clinical prognosis and patient management.

Direct detection of methicillin-resistant Staphylococcus aureus in sputum specimens from patients with hospital-associated pneumonia using a novel multilocus PCR assay.

Methicillin-resistant Staphylococcus aureus (MRSA) is a significant cause of hospital-associated pneumonia (HAP). The rapid identification of MRSA would be beneficial for early diagnosis. The study aimed to evaluate a multilocus, fluorescence-based PCR assay based on the detection of mecA and nuc genes for identification of S. aureusin lower respiratory tract (LRT) specimens. Sensitivity and specificity of the PCR assay were analyzed. Clinical evaluation for the assay was performed using LRT specimens from patients with HAP, and the sensitivity, specificity, positive and negative predictive values (PPV and NPV) were evaluated in comparison with semi-quantitative culture methods. The result showed the assay provided positive identification of all MRSA reference strains with a limit of detection for MRSA of 4 × 103 CFU/mL. Compared with semi-quantitative culture, the sensitivity, specificity, PPV and NPV were 100%, 89.6%, 75.0%, and 100%, respectively. A positive correlation between MRSA bacterial colonies and PCR copy number was found. The specificity and PPV reached 96.6% and 89.7% respectively, if the PCR copy number reached a definite positive threshold of 5.96 × 105. It suggested that this novel multilocus, fluorescence-based PCR assay proved to be a fast, sensitive and specific tool for direct detection of MRSA from LRT specimens.

STR DNA genotyping of hydatidiform moles in South China.

OBJECTIVE: To evacuate whether short-tandem-repeat (STR) DNA genotyping is effective for diagnostic measure to precisely classify hydatidiform moles. METHODS: 150 cases were selected based on histologic features that were previously diagnosed or suspected molar pregnancy. All sections were stained with hematoxylin as a quality control method, and guided the microscopic dissection. DNA was extracted from dissected chorionic villi and paired maternal endometrial FFPE tissue sections. Then, STR DNA genotyping was performed by AmpFlSTR(®) Sinofiler(TM) PCR Amplification system (Applied Biosystems, Inc). Data collection and analysis were carried out using GeneMapper(®) ID-X version 1.2 (Applied Biosystems, Inc). RESULTS: DNA genotyping was informative in all cases, leading to identification of 129 cases with abnormal genotype, including 95 complete and 34 partial moles, except 4 cases failed in PCR. Among 95 complete moles, 92 cases were monospermic and three were dispermic. Among 34 partial moles, 32 were dispermic and 2 were monospermic. The remaining 17 cases were balanced biallelic gestations. CONCLUSION: STR DNA genotyping is effective for diagnostic measure to precisely classify hydatidiform moles. And in the absence of laser capture microdissection (LCM), hematoxylin staining plus manual dissection under microscopic guided is a more economic and practical method.

GSK-3ß-regulated N-acetyltransferase 10 is involved in colorectal cancer invasion.

PURPOSE: NAT10 (N-acetyltransferase 10) is a nucleolar protein, but may show subcellular redistribution in colorectal carcinoma. In this study, we evaluated membranous staining of NAT10 in colorectal carcinoma and its clinical implications, and explored the mechanism of regulation of NAT10 redistribution. EXPERIMENTAL DESIGN: The expression and subcellular redistribution of NAT10, ß-catenin, E-cadherin, and GSK-3ß were evaluated by immunohistochemistry in 222 cases of colorectal carcinoma. Regulation of NAT10 and its influence on cell motility were analyzed with inhibitors of GSK-3ß, transfection of wild-type or kinase-inactivated GSK-3ß, or expression of various domains of NAT10, and evaluated with immunofluorescence, Western blotting, and Transwell assays. RESULTS: NAT10 localized mainly in the nucleoli of normal tissues, and was redistributed to the membrane in cancer cells, particularly at the invasive "leading edge" of the tumor. This correlated well with nuclear accumulation of ß-catenin (P<0.001; χ2=68.213). In addition, NAT10 membrane staining reflected the depth of invasion and tendency to metastasize (all P values<0.001), and was associated with a poorer prognosis (P=0.023; χ2=5.161). Evaluation of the mechanism involved demonstrated that subcellular redistribution of NAT10 may result from its increased stability and nuclear export, which is brought about by inhibition of GSK-3ß. Moreover, redistribution of NAT10 induces alteration of cytoskeletal dynamics and increases cancer cell motility. CONCLUSION: The subcellular redistribution of NAT10 can be induced by decreases in GSK-3ß activity. This redistribution increases cancer cell motility, and is, thus, correlated with invasive potential and poorer clinical outcome. This finding suggests that NAT10 may be a useful prognostic marker and potential therapeutic target in colorectal carcinoma.

Ethnicity determines association of p53Arg72Pro alleles with cervical cancer in China.

Minority Uigur women residing in Xinjiang, in the northwest of China, have a high incidence of cervical carcinoma (CC; 527/100 000) and are often diagnosed young. We favor the hypothesis that Uigur women may carry different genetic factor(s) making them more susceptible to CC than majority Han (Chinese) women living in the same region. Using PCR-restriction fragment length polymorphism, we investigated associations of a p53Arg72Pro polymorphism with CC in Uigur women compared with those in Han women. The study included 152 Uigur patients with CC and 110 controls, and 120 Han patients with CC and 122 controls. In Uigur women, CC was associated with p5372Arg/Arg homozygosity (chi=7.196, P<0.05) and with human papillomavirus-16 (chi=7.177, P<0.05). In Han women, however, CC was associated with p5372Pro/Pro homozygosity (chi=8.231, P<0.05). These observations suggest that individuals with different genetic backgrounds carry different susceptibilities to CC, at least in the Uigur and Han ethnic women studied in China.

[Correlation of telomere length and the expression of its regulating proteins in mesenchymal sarcomas].

OBJECTIVE: To explore the significance in the change of telomere length in mesenchymal sarcomas, through analyzing telomere length and expression of its associated proteins, including TRF1, POT1, hTERT, P53 and c-myc. METHODS: The telomere length in 20 cases of osteosarcomas, 25 of chondrosarcomas, 19 of rhabdomyosarcomas, 26 of liposarcomas was measured by telomere fluorescence in situ hybridization (Telo-FISH), and the expression of TRF1, POT1, hTERT, p53 or c-myc was analyzed by immunohistochemistry, respectively. RESULTS: The telomere length in osteosarcomas was significantly shorter than that of either chondrosarcomas or liposarcomas (P<0.05). Similarly, the telomere length of rhabdomyosarcoma was shorter than that of chondrosarcoma (P<0.05). Meanwhile, telomere shortening was positively correlated with down expression of telomere binding proteins TRF1 and POT1 (P<0.05), but trends were detected more frequently in positive expression of hTERT (P<0.05) and in nuclear accumulation of P53 or expression of c-myc. With advancing in histological grading, telomere length was shortened markedly in chondrosarcomas, especially in liposarcomas (P<0.05). CONCLUSION: The shortening of telomere could prevail in mesenchymal sarcoma and reflect the malignant potential. Telomere attrition usually correlated with down expression of POT1, TRF1 and with increased levels of hTERT, P53 and c-myc.

[Relationship between p53 Arg72Pro polymorphism and cervical carcinoma in Uigur and Han women in Xinjiang].

OBJECTIVE: To investigate the association between p53 Arg72Pro polymorphism and cervical carcinomas HPV-associated cervical carcinoma in Uigur and Han women. METHODS: The distribution and frequencies of p53 Arg72Pro genotypes were determined by PCR-RFLP in 152 cases of cervical carcinoma in ethnic Uigur women with 110 cases of normal control and 120 cases of cervical carcinoma in Han women with 122 cases of normal control. RESULTS: The omni-constituent ratio of p53 genotype was statistically different between cervical carcinoma and normal control groups in the Uigur (chi(2) = 7.196, P < 0.05) group. The proportion of Arg/Arg was higher in cervical carcinomas than that in control. The omni-constituent ratio of p53 genotype was statistically different between cervical carcinoma and normal control groups in Han (chi(2) = 8.231, P < 0.025). The proportion of Pro/Pro was higher in cervical carcinoma than that in normal control. The omni-constituent ratio was statistically different between HPV 16 positive and negative groups of cervical carcinoma in the Uigur group (chi(2) = 7.177, P < 0.05). The proportion of Arg/Arg was higher in HPV 16 positive group than that in HPV 16 negative group. CONCLUSIONS: p53 Arg72Pro polymorphism may be associated with the development of cervical carcinoma in Uigur and Han women in Xinjiang. p53 Arg/Arg genotype may be a genetically susceptible factor to HPV-associated cervical carcinoma in Uigur. p53 Pro/Pro genotype may be a genetically susceptible factor to cervical carcinoma in Han. There may be different susceptibilities to cervical cancer between Uigur and Han women in Xinjiang.