BACKGROUND For optimizing fecal immunochemical test(FIT)-based screening programs,reducing the rate of missed colorectal cancers(CRCs)by FIT(FIT-interval CRCs)is an important aspect.Knowledge of the molecular make-up ...BACKGROUND For optimizing fecal immunochemical test(FIT)-based screening programs,reducing the rate of missed colorectal cancers(CRCs)by FIT(FIT-interval CRCs)is an important aspect.Knowledge of the molecular make-up of these missed lesions could facilitate more accurate detection of all(precursor)lesions.AIM To compare the molecular make-up of FIT-interval CRCs to lesions that are detected by FIT[screen-detected CRCs(SD-CRCs)].METHODS FIT-interval CRCs observed in a Dutch pilot-program of FIT-based screening were compared to a control group of SD-CRCs in a 1:2 ratio,resulting in 27 FIT-interval CRC and 54 SD-CRCs.Molecular analyses included microsatellite instability(MSI),CpG island methylator phenotype(CIMP),DNA sequence mutations and copy number alterations(CNAs).RESULTS Although no significant differences were reached,FIT-interval CRCs were more often CIMP positive and MSI positive(33%CIMP in FIT-interval CRCs vs 21%in SD-CRCs(P=0.274);19%MSI in FIT-interval CRCs vs 12%in SD-CRCs(P=0.469)),and showed more often serrated pathway associated features such as BRAF(30%vs 12%,P=0.090)and PTEN(15%vs 2.4%,P=0.063)mutations.APC mutations,a classic feature of the adenoma-carcinoma-sequence,were more abundant in SD-CRCs(68%vs 40%in FIT-interval CRCs P=0.035).Regarding CNAs differences between the two groups;FIT-interval CRCs less often showed gains at the regions 8p11.22-q24.3(P=0.009),and more often gains at 20p13-p12.1(P=0.039).CONCLUSION Serrated pathway associated molecular features seem to be more common in FIT-interval CRCs,while classic adenoma carcinoma pathway associated molecular features seem to be more common in SD-CRCs.This indicates that proximal serrated lesions may be overrepresented among FITinterval CRCs.展开更多
AIM: To improve the interpretation of fecal immunochemical test (FIT) results in colorectal cancer (CRC) cases from screening and referral cohorts. METHODS: In this comparative observational study, two prospective coh...AIM: To improve the interpretation of fecal immunochemical test (FIT) results in colorectal cancer (CRC) cases from screening and referral cohorts. METHODS: In this comparative observational study, two prospective cohorts of CRC cases were compared. The first cohort was obtained from 10 322 average risk subjects invited for CRC screening with FIT, of which, only subjects with a positive FIT were referred for colonoscopy. The second cohort was obtained from 3637 subjects scheduled for elective colonoscopy with a positive FIT result. The same FIT and positivity threshold (OC sensor; ≥ 50 ng/mL) was used in both cohorts. Colonoscopy was performed in all referral subjects and in FIT positive screening subjects. All CRC cases were selected from both cohorts. Outcome measurements were mean FIT results and FIT scores per tissue tumor stage (T stage). RESULTS: One hundred and eighteen patients with CRC were included in the present study: 28 cases obtained from the screening cohort (64% male; mean age 65 years, SD 6.5) and 90 cases obtained from the referral cohort (58% male; mean age 69 years, SD 9.8). The mean FIT results found were higher in the referral cohort (829 ± 302 ng/mLvs 613 ± 368 ng/mL,P = 0.02). Tissue tumor stage (T stage) distribution was dif-ferent between both populations [screening population: 13 (46%) T1, eight (29%) T2, six (21%) T3, one (4%) T4 carcinoma; referral population: 12 (13%) T1, 22 (24%) T2, 52 (58%) T3, four (4%) T4 carcinoma], and higher T stage was significantly associated with higher FIT results (P < 0.001). Per tumor stage, no significant difference in mean FIT results was observed (screening vs referral: T1 498 ± 382 ng/mL vs 725 ± 374 ng/mL, P = 0.22; T2 787 ± 303 ng/mL vs 794 ± 341 ng/mL, P = 0.79; T3 563 ± 368 ng/mLvs 870 ± 258 ng/mL,P = 0.13; T4 not available). After correction for T stage in logistic regression analysis, no significant differences in mean FIT results were observed between both types of cohorts (P = 0.10). CONCLUSION: Differences in T stage distribution largely explain differences in FIT results between screening and referral cohorts. Therefore, FIT results should be reported according to T stage.展开更多
基金Supported by Foundation of Population Screening Mid-West Netherlands,Amsterdam,The Netherlands(BoMW)Foundation of Population Screening South-West Netherlands,Rotterdam,The Netherlands(BoZW)+2 种基金Netherlands Comprehensive Cancer Organization(IKNL)Netherlands Organization for Health Research and Development of the Dutch Ministry of Health(ZonMW)PALGA,the Nationwide Network and Registry of Histo-and Cytopathology in the Netherlands.
文摘BACKGROUND For optimizing fecal immunochemical test(FIT)-based screening programs,reducing the rate of missed colorectal cancers(CRCs)by FIT(FIT-interval CRCs)is an important aspect.Knowledge of the molecular make-up of these missed lesions could facilitate more accurate detection of all(precursor)lesions.AIM To compare the molecular make-up of FIT-interval CRCs to lesions that are detected by FIT[screen-detected CRCs(SD-CRCs)].METHODS FIT-interval CRCs observed in a Dutch pilot-program of FIT-based screening were compared to a control group of SD-CRCs in a 1:2 ratio,resulting in 27 FIT-interval CRC and 54 SD-CRCs.Molecular analyses included microsatellite instability(MSI),CpG island methylator phenotype(CIMP),DNA sequence mutations and copy number alterations(CNAs).RESULTS Although no significant differences were reached,FIT-interval CRCs were more often CIMP positive and MSI positive(33%CIMP in FIT-interval CRCs vs 21%in SD-CRCs(P=0.274);19%MSI in FIT-interval CRCs vs 12%in SD-CRCs(P=0.469)),and showed more often serrated pathway associated features such as BRAF(30%vs 12%,P=0.090)and PTEN(15%vs 2.4%,P=0.063)mutations.APC mutations,a classic feature of the adenoma-carcinoma-sequence,were more abundant in SD-CRCs(68%vs 40%in FIT-interval CRCs P=0.035).Regarding CNAs differences between the two groups;FIT-interval CRCs less often showed gains at the regions 8p11.22-q24.3(P=0.009),and more often gains at 20p13-p12.1(P=0.039).CONCLUSION Serrated pathway associated molecular features seem to be more common in FIT-interval CRCs,while classic adenoma carcinoma pathway associated molecular features seem to be more common in SD-CRCs.This indicates that proximal serrated lesions may be overrepresented among FITinterval CRCs.
基金Supported by A Research Grant of Center for Translational Molecular Medicine, The Netherlands, to van Turenhout STGrant of Nycomed B.V., Hoofddorp to "the Amsterdam Gut-club", The Netherlands+1 种基金The Netherlands Organization for Health Research and Development, ZonMW, No. 50-50115-98-060,project 63000004The original trial was registered under IS-RCTN57917442 at Current Controlled Trials (www.controlled-trials.com)
文摘AIM: To improve the interpretation of fecal immunochemical test (FIT) results in colorectal cancer (CRC) cases from screening and referral cohorts. METHODS: In this comparative observational study, two prospective cohorts of CRC cases were compared. The first cohort was obtained from 10 322 average risk subjects invited for CRC screening with FIT, of which, only subjects with a positive FIT were referred for colonoscopy. The second cohort was obtained from 3637 subjects scheduled for elective colonoscopy with a positive FIT result. The same FIT and positivity threshold (OC sensor; ≥ 50 ng/mL) was used in both cohorts. Colonoscopy was performed in all referral subjects and in FIT positive screening subjects. All CRC cases were selected from both cohorts. Outcome measurements were mean FIT results and FIT scores per tissue tumor stage (T stage). RESULTS: One hundred and eighteen patients with CRC were included in the present study: 28 cases obtained from the screening cohort (64% male; mean age 65 years, SD 6.5) and 90 cases obtained from the referral cohort (58% male; mean age 69 years, SD 9.8). The mean FIT results found were higher in the referral cohort (829 ± 302 ng/mLvs 613 ± 368 ng/mL,P = 0.02). Tissue tumor stage (T stage) distribution was dif-ferent between both populations [screening population: 13 (46%) T1, eight (29%) T2, six (21%) T3, one (4%) T4 carcinoma; referral population: 12 (13%) T1, 22 (24%) T2, 52 (58%) T3, four (4%) T4 carcinoma], and higher T stage was significantly associated with higher FIT results (P < 0.001). Per tumor stage, no significant difference in mean FIT results was observed (screening vs referral: T1 498 ± 382 ng/mL vs 725 ± 374 ng/mL, P = 0.22; T2 787 ± 303 ng/mL vs 794 ± 341 ng/mL, P = 0.79; T3 563 ± 368 ng/mLvs 870 ± 258 ng/mL,P = 0.13; T4 not available). After correction for T stage in logistic regression analysis, no significant differences in mean FIT results were observed between both types of cohorts (P = 0.10). CONCLUSION: Differences in T stage distribution largely explain differences in FIT results between screening and referral cohorts. Therefore, FIT results should be reported according to T stage.