The SMAP method offers higher sensitivity and specificity than alternative technologies, while eliminating the need for sequencing to identify mutations in the EGFR gene of NSCLC. It provides a robust and point-of-care accessible approach for a rapid identification of most patients likely to respond to gefitinib.

Palpable breast tumors can be definitively diagnosed based on a combination of physical examination, radiological studies and FNA, when the radiological studies concur with the diagnosis by FNA.

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We identified genes related to 5-fluorouracil (5-FU) sensitivity in colorectal cancer and utilized these genes for predicting the 5-FU sensitivity of liver metastases. Eighty-one candidate genes involved in 5-FU resistance in gastric and colon cancer cell lines were previously identified using a cDNA microarray. In this study, the mRNA expression levels of these 81 selected genes and the genes of 5-FUrelated enzymes, including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and orotate phosphoribosyltransferase (OPRT), were measured using real-time quantitative RT-PCR assays of surgically resected materials from primary colorectal tumors in 22 patients. Clinical responses were estimated by evaluating the effects of 5-FU-based hepatic artery injection (HAI) chemotherapy for synchronous liver metastases. Four genes (TNFRSF1B, SLC35F5, NAG-1 and OPRT) had significantly different expression profiles in 5-FU-nonresponding and responding tumors (p < 0.05). A ''Response Index'' system using three genes (TNFRSF1B, SLC35F5 and OPRT) was then developed using a discriminate analysis; the results were well correlated with the individual chemosensitivities. Among the 11 cases with positive scores in our response index, 9 achieved a reduction in their liver metastases after 5-FU-based chemotherapy, whereas only 1 of the 11 cases with negative scores responded well to chemotherapy. Our ''Response Index'' system, consisting of TNFRSF1B, SLC35F5 and OPRT, has great potential for predicting the efficacy of 5-FU-based chemotherapy against liver metastases from colorectal cancer. ' 2006 Wiley-Liss, Inc.Key words: 5-fluorouracil; chemosensitivity; colorectal cancer; liver metastasis; prediction Colorectal cancer is one of the most common malignancies and the second cause of death from cancer in the United States. 1 Recent improvements in early diagnosis and surgical therapy have facilitated the detection of early colorectal cancer and have contributed to a constantly decreasing death rate 1 ; however, some patients remain undiagnosed until their tumor has reached an advanced stage. The prognosis of patients with colorectal cancer depends on the stage of the disease. Patients with Dukes A disease have a good prognosis, but those with Dukes D disease, especially those with hepatic metastases, have a very poor prognosis.2 Furthermore, despite the complete curative resection of the primary tumor, many patients develop local or distant recurrences, and distant recurrences and metastatic tumors remain a major cause of death for patients with colorectal cancer.2 Therefore, the most efficacious strategy for improving surgical outcome in patients with colorectal cancer is to control distant recurrences and metastases effectively using neoadjuvant and adjuvant chemotherapy.5-Fluorouracil (5-FU) is the most frequently used chemotherapeutic agent for neoadjuvant and adjuvant chemotherapy against metastatic colorectal cancer. However, despite combined chemotherapy with 5-FU and other agents (Cisplatin, Leucovorin or Oxaliplatin...

Purpose: Aberrant activation of epidermal growth factor receptors (EGFR/HER1) by ligand stimulation or heterodimerization with human epidermal growth factor 2 (HER2) is considered to play an important role in the development of colorectal carcinoma. Amphiregulin (AR) is a ligand of EGFR that might be related to the development and progression of gastrointestinal tumors.The aim of this study was to determine the AR, EGFR, and HER2 protein expression levels and to evaluate their prognostic relevance to the clinical course of colorectal cancer. Experimental Design: The AR, EGFR, and HER2 protein levels in primary tumors of colorectal cancer (n = 106) were examined using immunohistochemistry. Metastatic sites in liver specimens (n = 16) were also analyzed in the same manner. Results: Thirteen (81.6%) metastatic lesions of the liver stained positive for AR. Among the primary lesions of colorectal cancer, 58 (54.7%) stained positive for AR, 13 (12.3%) stained positive for EGFR, and 5 (4.7%) stained positive for HER2. When the relationships between each protein expression level and the clinicopathologic factors were examined, only the AR expression level was significantly related to liver metastasis (P = 0.0296). A multivariate analysis of liver metastasis proved that AR expression was an independent prognostic factor of liver metastasis from colorectal cancer (P = 0.0217). Conclusions: AR expression in primary lesions of colorectal cancer is an important predictive marker of liver metastasis. Epidermal growth factor (EGF) receptors (EGFR) and theirvarious ligands seem to be involved in the progression of gastrointestinal tumors (1). The EGF signal pathway is reportedly activated by several kinds of stimulation. First, ligands like amphiregulin (AR), transforming growth factor-a (TGF-a), and EGF may bind to EGFR. EGFR, a 170-kDa transmembrane glycoprotein (2), is composed of an extracellular ligand-binding domain, a transmembrane region, and an intracellular protein tyrosine kinase domain (3 -5). The above-mentioned ligands bind to the extracellular ligand-binding domain of EGFR and stimulate the pathway. Second, the heterodimerization of EGFR and HER2 can reportedly stimulate signaling in the absence of ligands (2). These steps are followed by the stimulation of intrinsic tyrosine kinase activity and tyrosine autophosphorylation (3, 6 -8). Receptor activity is modulated by intracellular kinases that mediate negative feedback control via receptor phosphorylation at specific regulatory domains, and receptor inactivation is mediated by receptor internalization and ligandreceptor dissociation. AR has been implicated in the growth and regeneration of intestinal mucosa and might be related to the development and progression of gastrointestinal tumors (9 -12). Our microarray analysis in colorectal tumors and liver metastases revealed that AR was down-regulated in adenomatous tumors but was up-regulated in metastatic tumors of the liver (data not shown). These findings suggested that AR might contribute to liver meta...