ABSTRACT
BACKGROUND: Recent studies suggested substantial differences between primary tumors and metastases for EGFR expression in colorectal cancer (CRC). The aim of the study was to correlate the expression of a panel of molecular markers between primary CRC samples and metastases. METHODS: Expressions of EGFR, pEGFR, VEGF, pVEGF, PTEN, pAKT and p21 were analyzed in 28 primary tumors and 32 liver metastases by immunohistochemistry performed on formalin-fixed, paraffin-embedded sections from 46 CRC patients. The molecular profiles were evaluated by tissue micro-array. The correlation between tumor and metastasis biomarker expressions was tested. RESULTS: Among 60 CRC samples, 25% were EGFR positive, 38% were pEGFR positive, 38% were VEGF positive, 48% were pVEGF positive, 70% were pAKT positive and 51% were p21 positive. PTEN was deleted in 39% of cases and absence of p21 expression was found in 49% of cases. A significant correlation was observed between primary tumors and metastases for pAKT (p = 0.037) and pEGFR (p = 0.0002) status. In patients treated with cetuximab-based therapy (n = 18), p21 appeared as a significant predictive factor of response (p = 0.036). CONCLUSION: Biomarkers status may change between primary and metastatic sites in CRC, with potential implications for the identification of patients who are likely to respond to anti-EGFR treatment.
Subject(s)
Biomarkers, Tumor/metabolism , Colorectal Neoplasms/metabolism , Neoplasm Proteins/metabolism , Adult , Aged , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Antineoplastic Agents/therapeutic use , Bevacizumab , Camptothecin/analogs & derivatives , Camptothecin/therapeutic use , Cetuximab , Colorectal Neoplasms/drug therapy , Cyclin-Dependent Kinase Inhibitor p21 , ErbB Receptors/metabolism , Female , Humans , Irinotecan , Liver Neoplasms/metabolism , Liver Neoplasms/secondary , Lung Neoplasms/metabolism , Lung Neoplasms/secondary , Male , Middle Aged , PTEN Phosphohydrolase/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Vascular Endothelial Growth Factor A/metabolismABSTRACT
OBJECTIVES: Evaluate the improvement in detecting lung nodules when using multidetector CT (MDCT) computer-assisted diagnosis (CAD). MATERIAL AND METHODS: Three radiologists (R1, R2, R3) with different levels of experience independently interpreted 30 MDCT examinations of the thorax taken for screening purposes, first without and then with CAD. The diagnosis was established by two of the three radiologists interpreting the images together, assisted by the CAD. RESULTS: The consensus reading identified 133 nodules, 61 (46%) of which were 4 mm or larger. The sensitivity values in the detection of nodules before and after using the CAD were 54% and 80% (R1), 38% and 71% (R2), and 70% and 88% (R3), respectively. When considering only the nodules that were 4 mm or larger, the sensitivity values varied before and after using the CAD, from 62% to 95% (R1), from 41% to 84% (R2), and from 74% to 92% (R3). By combining two by two the three radiologists' results obtained without the CAD, the sensitivity values were 65%, 83%, and 77%, respectively, for all the nodules, and 70%, 85%, and 77% for the nodules that were 4 mm or larger. The CAD induced a total of 105 false-positive results, with a mean of 3.5 per examination. CONCLUSION: The lung nodules missed by the radiologist can be detected if the CAD is used as a second reader. The CAD can be at least as beneficial as the use of a second independent reader.
