Validation and simplification of Bethesda guidelines for identifying apparently sporadic forms of colorectal carcinoma with microsatellite instability.

BACKGROUND: Colorectal tumors with microsatellite instability (MSI) that do not comply with previously defined clinical criteria may be found in recently diagnosed hereditary nonpolyposis colorectal carcinoma families. Until recently, the indications for MSI testing were not clearly established. The objective of the current study was to validate the recently published Bethesda guidelines for MSI testing in a series of patients with apparently sporadic forms of colorectal carcinoma (CRC). METHODS: Sixty-two patients with so-called sporadic CRC were included in the current study. MSI was analyzed at seven poly(CA) repeat sequences and at one poly(A) locus. RESULTS: Nine of 62 patients (14.5%) had tumors exhibiting MSI at > or = 2 loci and 7 patients (11%) had MSI at > or = 3 loci. Patients with MSI positive tumors were younger (P < 0.05), and their tumors more frequently were right-sided (P < 0.02) and more often exhibited a mucinous component (P < 0.05). The Bethesda guidelines were positive in 18% (11 of 62) of patients. The sensitivity of these guidelines in identifying tumors with MSI at > or = 3 loci was 43% and the positive predictive value (PPV) was 27% (3 of 11 cases). Other variables were considered as alternative criteria to identify CRCs with MSI: age < 45 years and/or a right-sided tumor with a mucinous component. Using these 2 criteria alone, sensitivity increased to 85% and PPV to 46%. CONCLUSIONS: In this study group, the use of three clinical criteria as sole indicators for MSI testing in patients with apparently sporadic forms of CRC were significantly more discriminating compared with the Bethesda guidelines, in addition to being substantially easier.

High prevalence of human papillomavirus in squamous cell carcinoma and matched normal esophageal mucosa: assessment by polymerase chain reaction.

BACKGROUND: Studies using DNA technology have reported the presence of human papillomavirus (HPV) DNA in esophageal carcinomas, suggesting that it could play a role in the pathogenesis of this tumor. In the present study, in addition to DNA from neoplasms, normal mucosa was screened for viral DNA, assuming that this would increase HPV detection substantially. METHODS: Seventeen patients with esophageal carcinoma and 10 control subjects were studied. In 8 of the patients, normal mucosa was also available. Polymerase chain reaction (PCR) was performed using primers for the E6 region of HPV-16 and HPV-18. Koilocytosis, a commonly accepted histopathologic marker of viral infection, was studied, and results were correlated with PCR findings. RESULTS: DNA from neoplastic lesions was positive for HPV-16 and HPV-18 in 8 of 16 (50%) and in 3 of 16 (18.8%), respectively. When tumor tissue and normal mucosa were available, PCR results were 3 of 8 (37.5%), 5 of 8 (62.5%), and 8 of 8 (100%) for HPV-16, in tumor, normal mucosa, and both. For HPV-18, results were 0 of 8 (0%), 5 of 8 (62.5%), and 5 of 8 (62.5%), respectively. In comparison with tumor samples, positivity in normal mucosa was increased for HPV-18 and for both viral genotypes (P = 0.01). No amplification was obtained in the control group. Koilocytosis was present in 33% of the cases. CONCLUSIONS: These results suggested a high prevalence of HPV in esophageal carcinoma. The detection rate is significantly higher in normal mucosa specimens, suggesting that infection probably antedates tumor development. Koilocytosis was substantially less sensitive than PCR.

A diterpene from Mikania obtusata active on Trypanosoma cruzi.

The diterpene ent-kaur-16-en-19-oic acid (1) was identified as the trypanocidal component of the ethanolic extract from Mikania obtusata D. C. (Asteraceae). This compound presents an IC50 of 0.5 mg/ml (1.66 mM) against the trypomastigote blood form of the Trypanosoma cruzi, the causative agent of Chagas' disease (American trypanosomiasis).

Brine shrimp lethality assay as a prescreening system for anti-Trypanosoma cruzi activity.

With the aim of finding an acceptable method for selecting plant extracts to be assayed against the infective blood form of Trypanosoma cruzi, the causative agent of Chagas' disease (American trypanosomiasis), two different strategies were compared: a) screening only medicinal species and b) pre-screening random collected species in the brine shrimp lethality assay (BSLA). Fifty-two plants belonging to the Asteraceae family, including eighteen medicinal species, were collected and their ethanol extracts assayed against both T. cruzi and Artemia salina (brine shrimp). The proportion of trypanocidal extracts among the medicinal species and among the random collection did not differ significantly. On the other hand, the proportion of trypanocidal extracts among those that presented LC(50) of less than 100 ppm to A. salina was four times higher than among the medicinal species.