Genetic variations in angiogenesis pathway genes predict tumor recurrence in localized adenocarcinoma of the esophagus.

OBJECTIVE: The aim of this study was to determine whether the risk of systemic disease after esophagectomy could be predicted by angiogenesis-related gene polymorphisms. SUMMARY BACKGROUND DATA: Systemic tumor recurrence after curative resection continues to impose a significant problem in the management of patients with localized esophageal adenocarcinoma (EA). The identification of molecular markers of prognosis will help to better define tumor stage, indicate disease progression, identify novel therapeutic targets, and monitor response to therapy. Proteinase-activated-receptor 1 (PAR-1) and epidermal growth factor (EGF) have been shown to mediate the regulation of local and early-onset angiogenesis, and in turn may impact the process of tumor growth and disease progression. METHODS: We investigated tissue samples from 239 patients with localized EA treated with surgery alone. DNA was isolated from formalin-fixed paraffin-embedded normal esophageal tissue samples and polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism and 5'-end [gamma-P] ATP-labeled polymerase chain reaction methods. RESULTS: PAR-1 -506 ins/del (adjusted P value=0.011) and EGF +61 A>G (adjusted P value=0.035) showed to be adverse prognostic markers, in both univariate and multivariable analyses. In combined analysis, grouping alleles into favorable versus nonfavorable alleles, high expression variants of PAR-1 -506 ins/del (any insertion allele) and EGF +61 A>G (A/A) were associated with a higher likelihood of developing tumor recurrence (adjusted P value<0.001). CONCLUSION: This study supports the role of functional PAR-1 and EGF polymorphisms as independent prognostic markers in localized EA and may therefore help to identify patient subgroups at high risk for tumor recurrence.

Differentiation of cancerous lesions in excised human breast specimens using multiband attenuation profiles from ultrasonic transmission tomography.

OBJECTIVE: This study examines the tissue differentiation capability of the recently developed high-resolution ultrasonic transmission tomography (HUTT) system in the context of differentiating between benign and malignant tissue types in mastectomy specimens. METHODS: Eight mastectomy patients provided breast specimens with benign and malignant lesions. The specimens were scanned by the HUTT system with a pair of either 8- or 4-MHz transducers. Multiband HUTT images over the frequency range from 2 to 10 MHz provide characteristic profiles of frequency-dependent attenuation, termed "multiband profiles," at individual pixels. These features are classified through a novel algorithm of "segment-wise classification" that identifies the disjoint segments of various tissue types and subsequently classifies them into respective diagnostic categories using a measure of proximity to the respective multiband profile templates that have been previously obtained from reference data. RESULTS: We preformed intraspecimen and interspecimen analyses of 108 slices from 8 mastectomy specimens for which "ground truth" was provided by pathology reports. The average performance indices for 2-way classification (malignant versus nonmalignant tissue) in these intraspecimen (interspecimen) specimen studies were found to be sensitivity of 81.9% (89.6%), specificity of 92.9% (92.1%), and accuracy of 89.2% (89.4%), whereas the indices for the 3-way classification were moderately lower. CONCLUSIONS: The results have shown the potential of the HUTT technology for reliable differentiation of cancerous lesions from benign changes and normal tissue in mastectomy specimens using frequency-dependent ultrasound attenuation profiles.