MET amplification is not rare and predicts unfavorable clinical outcomes in patients with recurrent/metastatic gastric cancer after chemotherapy.
ABSTRACT Several large studies have reported an extremely low incidence of MET gene amplification (GA) in patients with radically resected gastric cancer. This study was conducted to evaluate the prevalence and prognostic role of MET in patients with recurrent=metastatic gastric cancer who received chemotherapy.
MET GA and protein expression of recurrent=metastatic gastric cancer samples were evaluated by fluorescence in situ hybridization and immunohistochemistry (IHC), respectively.
This retrospective study included 232 patients with recurrent=metastatic gastric cancer. MET GA and strong protein expression(IHC31) were observed in 8.3% (19 of 230 samples) and 9.6% (22 of 229 samples) of samples, respectively. A significant correlation was observed between MET GA and protein expression (r = 0.378; P<.001). MET GA was correlated with poor performance status(P<.001) and poorly differentiated tumors (P=.0015). Both MET GA and IHC 31 expression were associated with a substantially shorter median overall survival (OS) and progression-free survival (PFS). The median OS and PFS for patients with MET GA versus those without MET GA were 5.7 months versus 15.5 months (P<.001) and 3.6 months versus 6.9 months (P<.001), respectively. The median OS and PFS for patients with MET IHC 31 expression versus IHC 0 to 21 expression were 6.3 months versus 15.1 months(P<.001) and 3.6 months versus 7.0 months (P<.001), respectively.
In patients with recurrent=metastatic gastric cancer,MET amplification and strong protein expression are not rare and appear to be significantly associated with unfavorable clinical outcomes.
- SourceAvailable from: Federico Cappuzzo[Show abstract] [Hide abstract]
ABSTRACT: Gefitinib is a selective inhibitor of the epidermal growth factor (EGFR) tyrosine kinase, which is overexpressed in many cancers, including non-small-cell lung cancer (NSCLC). We carried out a clinical study to compare the relationship between EGFR gene copy number, EGFR protein expression, EGFR mutations, and Akt activation status as predictive markers for gefitinib therapy in advanced NSCLC. Tumors from 102 NSCLC patients treated daily with 250 mg of gefitinib were evaluated for EGFR status by fluorescence in situ hybridization (FISH), DNA sequencing, and immunohistochemistry and for Akt activation status (phospho-Akt [P-Akt]) by immunohistochemistry. Time to progression, overall survival, and 95% confidence intervals (CIs) were calculated and evaluated by the Kaplan-Meier method; groups were compared using the log-rank test. Risk factors associated with survival were evaluated using Cox proportional hazards regression modeling and multivariable analysis. All statistical tests were two-sided. Amplification or high polysomy of the EGFR gene (seen in 33 of 102 patients) and high protein expression (seen in 58 of 98 patients) were statistically significantly associated with better response (36% versus 3%, mean difference = 34%, 95% CI = 16.6 to 50.3; P<.001), disease control rate (67% versus 26%, mean difference = 40.6%, 95% CI = 21.5 to 59.7; P<.001), time to progression (9.0 versus 2.5 months, mean difference = 6.5 months, 95% CI = 2.8 to 10.3; P<.001), and survival (18.7 versus 7.0 months, mean difference = 11.7 months, 95% CI = 2.1 to 21.4; P = .03). EGFR mutations (seen in 15 of 89 patients) were also statistically significantly related to response and time to progression, but the association with survival was not statistically significant, and 40% of the patients with mutation had progressive disease. In multivariable analysis, only high EGFR gene copy number remained statistically significantly associated with better survival (hazard ratio = 0.44, 95% CI = 0.23 to 0.82). Independent of EGFR assessment method, EGFR+/P-Akt+ patients had a statistically significantly better outcome than EGFR-, P-Akt-, or EGFR+/P-Akt- patients. High EGFR gene copy number identified by FISH may be an effective molecular predictor for gefitinib efficacy in advanced NSCLC.CancerSpectrum Knowledge Environment 05/2005; 97(9):643-55. · 14.07 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Efforts to reduce global cancer disparities begin with an understanding of geographic patterns in cancer incidence, mortality, and prevalence. Using the GLOBOCAN (2002) and Cancer Incidence in Five Continents databases, we describe overall cancer incidence, mortality, and prevalence, age-adjusted temporal trends, and age-specific incidence patterns in selected geographic regions of the world. For the eight most common malignancies-cancers of lung, breast, colon and rectum, stomach, prostate, liver, cervix, and esophagus-the most important risk factors, cancer prevention and control measures are briefly reviewed. In 2002, an estimated 11 million new cancer cases and 7 million cancer deaths were reported worldwide; nearly 25 million persons were living with cancer. Among the eight most common cancers, global disparities in cancer incidence, mortality, and prevalence are evident, likely due to complex interactions of nonmodifiable (ie, genetic susceptibility and aging) and modifiable risk factors (ie, tobacco, infectious agents, diet, and physical activity). Indeed, when risk factors among populations are intertwined with differences in individual behaviors, cultural beliefs and practices, socioeconomic conditions, and health care systems, global cancer disparities are inevitable. For the eight most common cancers, priorities for reducing cancer disparities are discussed.Journal of Clinical Oncology 06/2006; 24(14):2137-50. · 17.88 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Gastric cancer is one of the most frequent cancers in the world; almost two-thirds of gastric cancer cases and deaths occur in less developed regions. In China, based on two national mortality surveys conducted in 1970s and 1990s, there is an obvious clustering of geographical distribution of gastric cancer in the country, with the high mortality being mostly located in rural areas, especially in Gansu, Henan, Hebei, Shanxi and Shaanxi Provinces in the middle-western part of China. Despite a slight increase from the 1970s to early 1990s, remarkable declines in gastric cancer mortality were noticed in almost the entire population during the last decade in China. These declines were largely due to the dramatic improvements in the social-economic environment, lifestyle, nutrition, education and health care system after economic reforms started two decades ago. Nevertheless, gastric cancer will remain a significant cancer burden currently and be one of the key issues in cancer prevention and control strategy in China. It was predicted that, in 2005, 0.3 million deaths and 0.4 million new cases from gastric cancer would rank the third most common cancer. The essential package of the prevention and control strategy for gastric cancer in China would focus on controlling Helicobacter pylori (H. pylori) infection, improving educational levels, advocating healthy diet and anti-tobacco campaign, searching for cost-effective early detection, diagnosis and treatment programs including approaches for curable management and palliative care.World Journal of Gastroenterology 02/2006; 12(1):17-20. · 2.43 Impact Factor