***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: A multicenter phase II trial was conducted to define the activity of letrozole in postmenopausal women with recurrent or advanced endometrial carcinoma , who had no more than one prior line of progestins and never had chemotherapy ( except adjuvant ) . Archival paraffin-embedded tumor sample s were retrieved to determine the expression level of estrogen ( ER ) and progesterone receptor ( PgR ) , p53 , HER-2 , bcl-2 and PTEN protein , and phosphorylation status of protein kinase B ( PKB/Akt ) .  Thirty-two eligible patients were treated with letrozole at 2.5 mg daily continuously , of whom 10 ( 31 % )  had prior progestins . Of the 28 patients evaluated for response , one complete and two partial responses were noted ; overall response was 9.4 % ( 95 % confidence interval 2–25 % ) . Eleven patients had stable disease for a median duration of 6.7 months ( range 3.7–19.3 months ) . Amongst 22 patients who had tumor blocks available , the proportion showing positive expression of the following markers includes : PgR ( 86 % ) , ER ( 86 % ) , PTEN ( 82 % ) , phosphorylated PKB/Akt ( 59 % ) , bcl-2 ( 45 % ) , p53 ( 32 % ) , and HER-2 ( 0 % ) . None of these markers correlated with response to letrozole or disease progression . In conclusion , letrozole is well tolerated but has little overall activity in this cohort of women with endometrial cancer CONTEXT The selection of individuals for hereditary nonpolyposis colorectal cancer ( HNPCC ) genetic testing is challenging . Recently , the National Cancer Institute outlined a new set of recommendations , the revised Bethesda guidelines , for the identification of individuals with HNPCC who should be tested for microsatellite instability . OBJECTIVE To establish the most effective and efficient strategy for the detection of MSH2/MLH1 gene carriers . DESIGN , SETTING , AND PATIENTS A prospect i ve , multicenter , nationwide study ( the EPICOLON study ) in 20 hospitals in the general community in Spain of 1222 patients with newly diagnosed colorectal cancer between November 1 , 2000 , and October 31 , 2001 . INTERVENTIONS Microsatellite instability testing and MSH2/MLH1 immunostaining in all patients regardless of age , personal or family history , and tumor characteristics . Patients whose tumors exhibited microsatellite instability and /or lack of protein expression underwent MSH2/MLH1 germline testing . MAIN OUTCOME MEASURES Effectiveness and efficiency of both microsatellite instability testing and immunostaining  , either directly or previous selection of patients according to the revised Bethesda guidelines , were evaluated with respect to the presence of MSH2/MLH1 germline mutations . RESULTS Two hundred eighty-seven patients ( 23.5 % ) fulfilled the revised Bethesda guidelines . Ninety-one patients ( 7.4 % ) had a mismatch repair deficiency  , with tumors exhibiting either microsatellite instability ( n = 83 ) or loss of protein expression ( n = 81 ) . Germline testing identified 11 mutations ( 0.9 % ) in either MSH2 ( 7 cases ) or MLH1 ( 4 cases ) genes . Strategies based on either  microsatellite instability testing or immunostaining previous selection of patients according to the revised Bethesda guidelines were the most effective ( sensitivity , 81.8 % and 81.8 % ; specificity , 98.0 % and 98.2 % ; positive predictive value , 27.3 % and 29.0 % , respectively ) to identify MSH2/MLH1 gene carriers . Logistic regression analysis confirmed the revised Bethesda guidelines as the most discriminating set of clinical parameters ( odds ratio , 33.3 ; 95 % confidence interval , 4.3 - 250 ; P = .001 ) . CONCLUSION The revised Bethesda guidelines constitute a useful approach to identify patients at risk for HNPCC . In patients fulfilling these criteria , both microsatellite instability testing and immunostaining are equivalent and highly effective strategies to further select those patients who should be tested for MSH2/MLH1 germline mutations PURPOSE Most studies of  microsatellite instability ( MSI ) and outcomes in endometrial cancer patients have included varied histologic subtypes . Nonetheless , MSI occurs almost exclusively in endometrioid tumors . The impact of MSI on outcomes in patients with endometrial cancer is controversial . We sought to determine whether MSI and MLH1 methylation are associated with clinicopathologic variables and survival outcomes in a large series of patients with endometrial carcinomas of the endometrioid type . PATIENTS AND METHODS Tumor sample s , blood , and clinicopathologic data were prospect ively collected and analyzed for 446 patients with endometrioid carcinomas .  MSI was determined using five National Cancer Institute ( NCI ) consensus panel markers , and the methylation status of the MLH1 promoter was determined by combined bisulfite restriction analysis ( COBRA ) . Associations with clinicopathologic variables and survival outcomes were evaluated . RESULTS MSI was identified in 147 cases ( 33 % ) . MSI was associated with higher International Federation of Gynecology and Obstetrics ( FIGO ) grade ( P < .0001 ) . MSI+ tumors without MLH1 methylation were associated with younger age ( P < .001 ) . MSI was not associated with overall survival ( OS ; hazard ratio [ HR ] , 1.011 ; 95 % CI , 0.688 to 1.484 ; P = .96 ) or disease-free survival ( DFS ; HR 0.951 ; 95 % CI , 0.554 to 1.635 ; P = .86 ) . The combined MSI/MLH1 methylation status ( treating MSI- as the reference ) did not predict OS ( MSI+/MLH1-U : HR , 0.62 ; 95 % CI , 0.27 to 1.44 ; P = .26 ; MSI+/MLH1-M : HR , 0.95 ; 95 % CI , 0.62 to 1.46 ; P = .82 ) or DFS ( MSI+/MLH1-U : HR , 0.51 ; 95 % CI , 0.22 to 1.19 ; P = .12 ; MSI+/MLH1-M : HR , 0.93 ; 95 % CI , 0.62 to 1.40 ; P = .72 ) . CONCLUSION MSI is not associated with survival in patients with endometrioid endometrial cancer PURPOSE Prior reports have indicated that patients with colon cancer who demonstrate high-level microsatellite instability ( MSI-H ) or defective DNA mismatch repair ( dMMR ) have improved survival and receive no benefit from fluorouracil ( FU ) -based adjuvant therapy compared with patients who have microsatellite-stable or proficient mismatch repair ( pMMR ) tumors . We examined MMR status as a predictor of adjuvant therapy benefit in patients with stages II and III colon cancer . METHODS MSI assay or immunohistochemistry for MMR proteins were performed on 457 patients who were previously r and omly assigned to FU-based therapy ( either FU + levamisole or FU + leucovorin ; n = 229 ) versus no postsurgical treatment ( n = 228 ) . Data were subsequently pooled with data from a previous analysis . The primary end point was disease-free survival ( DFS ) . RESULTS Overall , 70 ( 15 % ) of 457 patients exhibited dMMR . Adjuvant therapy significantly improved DFS ( hazard ratio [ HR ] , 0.67 ; 95 % CI , 0.48 to 0.93 ; P = .02 ) in patients with pMMR tumors . Patients with dMMR tumors receiving FU had no improvement in DFS ( HR , 1.10 ; 95 % CI , 0.42 to 2.91 ; P = .85 ) compared with those r and omly assigned to surgery alone . In the pooled data set of 1,027 patients ( n = 165 with dMMR ) , these findings were maintained ; in patients with stage II disease and with dMMR tumors , treatment was associated with reduced overall survival ( HR , 2.95 ; 95 % CI , 1.02 to 8.54 ; P = .04 ) . CONCLUSION Patient stratification by MMR status may provide a more tailored approach to colon cancer adjuvant therapy . These data support MMR status assessment for patients being considered for FU therapy alone and consideration of MMR status in treatment decision making 
    Output:
    
There is no definitive evidence of a significant association between MMR status and detrimental survival in endometrial cancer