20:
392:
416:(active in the mismatch DNA repair pathway). The percent of crypts in 6 tissue samples taken within the field defect were evaluated for frequency of high levels of expression of each of the repair proteins. Almost every crypt in all tissue samples from this patient showed high expression of KU86. However, the majority of crypts in all 6 tissue samples were reduced or absent in protein expression of ERCC1 and PMS2. The crypts with reduced or absent expression of ERCC1 or PMS2 usually occurred in large patches of adjacent crypts. Both ERCC1 and PMS2, in these tissue samples, were thought to be deficient due to epigenetic alterations.
400:
The field defect adjacent to a colon cancer consists of the inner surface of the colon (the epithelium) that has about 1 million crypts (indentations in the surface of the epithelium). Each crypt has about 5,000 cells in the shape of a test-tube and all 5,000 cells of the crypt are generated from the
395:
A colon cancer resection, 22 cm long, had 6 tissue samples evaluated for expression of 3 DNA repair proteins, Ku86, ERCC1 and PMS2. All 3 proteins are expressed at near 100% in colon tissue from a person without any colonic neoplasia, but adjacent to a colon cancer, in this instance, there is a field
1142:
Svrcek M, Buhard O, Colas C, Coulet F, Dumont S, Massaoudi I, Lamri A, Hamelin R, Cosnes J, Oliveira C, Seruca R, Gaub MP, Legrain M, Collura A, Lascols O, Tiret E, FlΓ©jou JF, Duval A (November 2010). "Methylation tolerance due to an O6-methylguanine DNA methyltransferase (MGMT) field defect in the
23:
Longitudinally opened freshly resected colon segment showing a cancer and four polyps. Plus a schematic diagram indicating a likely field defect (a region of tissue that precedes and predisposes to the development of cancer) in this colon segment. The diagram indicates sub-clones and sub-sub-clones
146:
A common carcinogenic alteration, found in many cancers and in their adjacent field defects from which the cancers likely arose, is reduced expression of one or more DNA repair enzymes. Since reduced DNA repair expression is often present in a field cancerization or a field defect, it is likely to
382:
Field defects associated with gastrointestinal tract cancers also commonly displayed reduced apoptosis competence, aberrant proliferation and genomic instability. Field defects of the gastrointestinal tract that show those common faults occurred in the oropharynx, esophagus, stomach, bile duct,
401:
few stem cells at the base of the crypt. The stem cells at the base of the crypt can undergo "crypt conversion" where a stem cell with a selective advantage takes over the stem cell niche, and all cells of that crypt display consistent expression (high or low) of a protein being evaluated.
455:
Rubin H (March 2011). "Fields and field cancerization: the preneoplastic origins of cancer: asymptomatic hyperplastic fields are precursors of neoplasia, and their progression to tumors can be tracked by saturation density in culture".
1274:
Zuo C, Zhang H, Spencer HJ, Vural E, Suen JY, Schichman SA, Smoller BR, Kokoska MS, Fan CY (October 2009). "Increased microsatellite instability and epigenetic inactivation of the hMLH1 gene in head and neck squamous cell carcinoma".
1238:
Paluszczak J, Misiak P, Wierzbicka M, WoΕΊniak A, Baer-Dubowska W (February 2011). "Frequent hypermethylation of DAPK, RARbeta, MGMT, RASSF1A and FHIT in laryngeal squamous cell carcinomas and adjacent normal mucosa".
1106:
Lee KH, Lee JS, Nam JH, Choi C, Lee MC, Park CS, Juhng SW, Lee JH (October 2011). "Promoter methylation status of hMLH1, hMSH2, and MGMT genes in colorectal cancer associated with adenoma-carcinoma sequence".
107:. The image of a longitudinally opened colon resection on this page shows an area of a colon resection that likely has a field cancerization or field defect. It has one cancer and four premalignant polyps.
19:
1310:
Tawfik HM, El-Maqsoud NM, Hak BH, El-Sherbiny YM (2011). "Head and neck squamous cell carcinoma: mismatch repair immunohistochemistry and promoter hypermethylation of hMLH1 gene".
1062:
Shen L, Kondo Y, Rosner GL, Xiao L, Hernandez NS, Vilaythong J, Houlihan PS, Krouse RS, Prasad AR, Einspahr JG, Buckmeier J, Alberts DS, Hamilton SR, Issa JP (September 2005).
404:
The diagram shows results obtained by
Facista et al. A particular colon resection from a colon cancer patient was evaluated for expression of 3 different DNA repair enzymes:
775:
Wu X, Hu Y, Lippman SM. Upper
Aerodigestive Tract Cancers. page 325 in Neugut AI, Meadows AT, Robinson E. Multiple Primary Cancers. Lippincott Williams & Wilkins, 1999.
1345:
Zou XP, Zhang B, Zhang XQ, Chen M, Cao J, Liu WJ (November 2009). "Promoter hypermethylation of multiple genes in early gastric adenocarcinoma and precancerous lesions".
1187:
Facista A, Nguyen H, Lewis C, Prasad AR, Ramsey L, Zaitlin B, Nfonsam V, Krouse RS, Bernstein H, Payne CM, Stern S, Oatman N, Banerjee B, Bernstein C (2012).
440:
Field cancerization
Medical Dictionary - The Free Dictionary McGraw-Hill Concise Dictionary of Modern Medicine. 2002 by The McGraw-Hill Companies, Inc.
391:
1000:
Cheng L, Davidson DD, Maclennan GT, Williamson SR, Zhang S, Koch MO, Montironi R, Lopez-Beltran A (Jun 2010). "The origins of urothelial carcinoma".
921:
Debruyne PR, Witek M, Gong L, Birbe R, Chervoneva I, Jin T, Domon-Cell C, Palazzo JP, Freund JN, Li P, Pitari GM, Schulz S, Waldman SA (April 2006).
126:, skin, breast ducts and bladder. Field cancerization has implications for cancer surveillance and treatment. Despite adequate resection and being
965:
Rivenbark AG, Coleman WB (Dec 2012). "Field cancerization in mammary carcinogenesis -Implications for prevention and treatment of breast cancer".
550:
Braathen LR, Morton CA, Basset-Seguin N, Bissonnette R, Gerritsen MJ, Gilaberte Y, Calzavara-Pinton P, Sidoroff A, Wulf HC, Szeimies RM (2012).
552:"Photodynamic therapy for skin field cancerization: an international consensus. International Society for Photodynamic Therapy in Dermatology"
923:"Bile acids induce ectopic expression of intestinal guanylyl cyclase C through nuclear factor-kappaB and Cdx2 in human esophageal cells"
151:
Frequency of finding epigenetic reductions in protein expression of DNA repair genes in sporadic cancers and in adjacent field defects
1531:
1514:
1039:
110:
Field cancerization can occur in any tissue. Prominent examples of field cancerization include premalignant field defects in
1618:
684:
Heaphy CM, Griffith JK, Bisoffi M (Nov 2009). "Mammary field cancerization: molecular evidence and clinical importance".
87:
changes, occurring over a widespread, multi-focal "field". These initial molecular changes may subsequently progress to
130:
normal, the remaining locoregional tissue has an increased risk for developing multiple independent cancers, either
1050:
Kufe, DW; Holland, JF; Frei, E; Cancer medicine. 6th ed. pages 1391 and 2625. BC Decker, 2003. NLM ID 101189332
872:
Gong L, Debruyne PR, Witek M, Nielsen K, Snook A, Lin JE, Bombonati A, Palazzo J, Schulz S, Waldman SA (2009).
874:"Bile acids initiate lineage-addicted gastroesophageal tumorigenesis by suppressing the EGF receptor-AKT axis"
646:
Vatve M, Ortonne JP, Birch-Machin MA, Gupta G (Dec 2007). "Management of field change in actinic keratosis".
1382:"Promoter methylation status of DNA repair gene (hMLH1) in gastric carcinoma patients of the Kashmir valley"
1515:"Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin"
123:
1423:"Role of epigenetic alterations in the pathogenesis of Barrett's esophagus and esophageal adenocarcinoma"
1143:
colonic mucosa: an initiating step in the development of mismatch repair-deficient colorectal cancers".
1034:
Dakubo GD. Field
Cancerization: Basic Science and Clinical Applications. Nova Science Publishers, 2010.
441:
79:
The initial step in field cancerization is associated with various molecular lesions such as acquired
1581:
Leemans, CR; Braakhuis, BJM; Brakenhoff RH. (January 2011). "Field cancerization and local relapse".
798:
111:
498:"Wistuba II Field cancerization in non-small cell lung cancer: implications in disease pathogenesis"
1421:
Agarwal A, Polineni R, Hussein Z, Vigoda I, Bhagat TD, Bhattacharyya S, Maitra A, Verma A (2012).
1598:
1570:
1536:
1493:
1444:
1403:
1362:
1327:
1292:
1256:
1220:
1160:
1124:
1085:
1035:
1017:
982:
944:
903:
854:
824:
755:
701:
663:
625:
573:
527:
473:
119:
100:
71:. The process arises from exposure to an injurious environment, often over a lengthy period.
1590:
1560:
1526:
1483:
1475:
1434:
1393:
1354:
1319:
1284:
1248:
1210:
1200:
1152:
1116:
1075:
1009:
974:
934:
893:
885:
814:
806:
745:
737:
693:
655:
615:
607:
563:
517:
509:
465:
80:
60:
1189:"Deficient expression of DNA repair enzymes in early progression to sporadic colon cancer"
64:
802:
1488:
1463:
1439:
1422:
1252:
1215:
1188:
898:
873:
819:
786:
785:
Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA, Kinzler KW (March 2013).
750:
725:
620:
595:
522:
497:
68:
56:
845:
Zeki SS, McDonald SA, Graham TA (2011). "Field cancerization in
Barrett's esophagus".
1612:
889:
659:
568:
551:
726:"Cutaneous field cancerization: clinical, histopathological and therapeutic aspects"
135:
1565:
1548:
92:
1358:
741:
1479:
1398:
1381:
1323:
1288:
939:
922:
978:
131:
115:
1380:
Wani M, Afroze D, Makhdoomi M, Hamid I, Wani B, Bhat G, Wani R, Wani K (2012).
1120:
1051:
697:
513:
84:
1156:
810:
127:
96:
1602:
1574:
1540:
1532:
10.1002/1097-0142(195309)6:5<963::AID-CNCR2820060515>3.0.CO;2-Q
1497:
1448:
1407:
1366:
1331:
1296:
1260:
1224:
1164:
1128:
1089:
1021:
986:
948:
907:
858:
828:
759:
705:
667:
629:
577:
531:
477:
469:
1205:
1080:
1064:"MGMT promoter methylation and field defect in sporadic colorectal cancer"
1063:
1462:
Bernstein C, Bernstein H, Payne CM, Dvorak K, Garewal H (February 2008).
88:
611:
1013:
104:
1594:
396:
of more than 20 cm in which ERCC1 and PMS2 have reduced expression.
409:
1464:"Field defects in progression to gastrointestinal tract cancers"
413:
405:
1549:"Second Field Tumors: A New Opportunity for Cancer Prevention?"
1547:
Braakhuis, B. J. M.; Brakenhoff, R. H.; Leemans, C. R. (2005).
412:(active in the nucleotide excision DNA repair pathway) and
1513:
Slaughter, D. P.; Southwick, H. W.; Smejkal, W. (1953).
147:
have been an early step in progression to the cancer.
408:(active in the non-homologous end joining pathway),
596:"Evidence for field cancerization of the prostate"
55:) is a biological process in which large areas of
436:
434:
432:
430:
428:
960:
958:
594:Nonn L, Ananthanarayanan V, Gann PH (Sep 2009).
1101:
1099:
545:
543:
541:
719:
717:
715:
8:
679:
677:
502:Proceedings of the American Thoracic Society
491:
489:
487:
383:pancreas, small intestine and colon/rectum.
840:
838:
641:
639:
450:
448:
1182:
1180:
1178:
1176:
1174:
589:
587:
149:
1564:
1530:
1487:
1438:
1397:
1214:
1204:
1079:
938:
897:
818:
749:
619:
567:
521:
771:
769:
390:
387:Pattern of alterations in a field defect
18:
424:
724:Torezan LA, Festa-Neto C (Oct 2013).
142:Common early carcinogenic alterations
7:
24:that were precursors to the tumors.
1253:10.1016/j.oraloncology.2010.11.006
14:
890:10.1111/j.1752-8062.2009.00131.x
660:10.1111/j.1365-2133.2007.08268.x
569:10.1111/j.1468-3083.2011.04432.x
1566:10.1634/theoncologist.10-7-493
1:
1359:10.1016/j.humpath.2009.01.029
742:10.1590/abd1806-4841.20132300
1480:10.1016/j.canlet.2007.11.027
1399:10.7314/APJCP.2012.13.8.4177
1324:10.1016/j.amjoto.2010.11.005
1289:10.1016/j.otohns.2009.07.007
940:10.1053/j.gastro.2005.12.032
556:J Eur Acad Dermatol Venereol
979:10.1016/j.yexmp.2012.10.018
1635:
1277:Otolaryngol Head Neck Surg
1002:Expert Rev Anticancer Ther
787:"Cancer genome landscapes"
41:field change cancerization
1386:Asian Pac. J. Cancer Prev
1121:10.1007/s00423-011-0812-9
698:10.1007/s10549-009-0504-0
514:10.1513/pats.201201-004MS
165:Frequency in Field Defect
53:premalignant field defect
69:carcinogenic alterations
1157:10.1136/gut.2009.194787
811:10.1126/science.1235122
686:Breast Cancer Res Treat
470:10.1002/bies.201000067
397:
25:
1583:Nature Reviews Cancer
1427:Int J Clin Exp Pathol
1206:10.1186/2041-9414-3-3
1109:Langenbecks Arch Surg
496:Kadara H (May 2012).
394:
63:surface or within an
22:
1619:Biological processes
1068:J. Natl. Cancer Inst
112:head and neck cancer
99:, and eventually to
45:field carcinogenesis
1081:10.1093/jnci/dji275
803:2013Sci...339.1546V
162:Frequency in Cancer
152:
124:Barrett's esophagus
49:cancer field effect
29:Field cancerization
612:10.1002/pros.20983
398:
150:
26:
16:Biological process
1014:10.1586/era.10.73
797:(6127): 1546β58.
654:(Suppl 2): 21β4.
380:
379:
120:colorectal cancer
101:carcinoma in situ
81:genetic mutations
1626:
1606:
1578:
1568:
1544:
1534:
1502:
1501:
1491:
1459:
1453:
1452:
1442:
1418:
1412:
1411:
1401:
1377:
1371:
1370:
1342:
1336:
1335:
1312:Am J Otolaryngol
1307:
1301:
1300:
1271:
1265:
1264:
1235:
1229:
1228:
1218:
1208:
1184:
1169:
1168:
1139:
1133:
1132:
1103:
1094:
1093:
1083:
1059:
1053:
1048:
1042:
1032:
1026:
1025:
997:
991:
990:
962:
953:
952:
942:
927:Gastroenterology
918:
912:
911:
901:
869:
863:
862:
842:
833:
832:
822:
782:
776:
773:
764:
763:
753:
730:An Bras Dermatol
721:
710:
709:
681:
672:
671:
643:
634:
633:
623:
591:
582:
581:
571:
547:
536:
535:
525:
493:
482:
481:
452:
443:
438:
153:
67:are affected by
1634:
1633:
1629:
1628:
1627:
1625:
1624:
1623:
1609:
1608:
1595:10.1038/nrc2982
1580:
1579:
1546:
1545:
1512:
1510:
1505:
1461:
1460:
1456:
1420:
1419:
1415:
1379:
1378:
1374:
1353:(11): 1534β42.
1344:
1343:
1339:
1309:
1308:
1304:
1273:
1272:
1268:
1237:
1236:
1232:
1186:
1185:
1172:
1151:(11): 1516β26.
1141:
1140:
1136:
1105:
1104:
1097:
1061:
1060:
1056:
1049:
1045:
1033:
1029:
999:
998:
994:
964:
963:
956:
933:(4): 1191β206.
920:
919:
915:
878:Clin Transl Sci
871:
870:
866:
844:
843:
836:
784:
783:
779:
774:
767:
723:
722:
713:
683:
682:
675:
645:
644:
637:
593:
592:
585:
549:
548:
539:
495:
494:
485:
454:
453:
446:
439:
426:
422:
389:
144:
77:
17:
12:
11:
5:
1632:
1630:
1622:
1621:
1611:
1610:
1559:(7): 493β500.
1553:The Oncologist
1525:(5): 963β968.
1509:
1508:External links
1506:
1504:
1503:
1454:
1413:
1392:(8): 4177β81.
1372:
1337:
1302:
1266:
1230:
1170:
1134:
1115:(7): 1017β26.
1095:
1074:(18): 1330β8.
1054:
1043:
1027:
992:
967:Exp Mol Pathol
954:
913:
864:
834:
777:
765:
711:
673:
635:
606:(13): 1470β9.
583:
537:
483:
444:
423:
421:
418:
388:
385:
378:
377:
375:
372:
369:
366:
362:
361:
359:
356:
353:
350:
346:
345:
343:
340:
337:
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330:
329:
327:
324:
321:
318:
317:Head and Neck
314:
313:
311:
308:
305:
302:
301:Head and Neck
298:
297:
295:
292:
289:
286:
285:Head and Neck
282:
281:
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273:
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266:
265:
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257:
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185:
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163:
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157:
143:
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136:metachronously
128:histologically
76:
73:
15:
13:
10:
9:
6:
4:
3:
2:
1631:
1620:
1617:
1616:
1614:
1607:
1604:
1600:
1596:
1592:
1588:
1584:
1576:
1572:
1567:
1562:
1558:
1554:
1550:
1542:
1538:
1533:
1528:
1524:
1520:
1516:
1507:
1499:
1495:
1490:
1485:
1481:
1477:
1474:(1β2): 1β10.
1473:
1469:
1465:
1458:
1455:
1450:
1446:
1441:
1436:
1433:(5): 382β96.
1432:
1428:
1424:
1417:
1414:
1409:
1405:
1400:
1395:
1391:
1387:
1383:
1376:
1373:
1368:
1364:
1360:
1356:
1352:
1348:
1341:
1338:
1333:
1329:
1325:
1321:
1318:(6): 528β36.
1317:
1313:
1306:
1303:
1298:
1294:
1290:
1286:
1283:(4): 484β90.
1282:
1278:
1270:
1267:
1262:
1258:
1254:
1250:
1246:
1242:
1234:
1231:
1226:
1222:
1217:
1212:
1207:
1202:
1198:
1194:
1193:Genome Integr
1190:
1183:
1181:
1179:
1177:
1175:
1171:
1166:
1162:
1158:
1154:
1150:
1146:
1138:
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1126:
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1118:
1114:
1110:
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1100:
1096:
1091:
1087:
1082:
1077:
1073:
1069:
1065:
1058:
1055:
1052:
1047:
1044:
1041:
1040:9781617610066
1037:
1031:
1028:
1023:
1019:
1015:
1011:
1008:(6): 865β80.
1007:
1003:
996:
993:
988:
984:
980:
976:
972:
968:
961:
959:
955:
950:
946:
941:
936:
932:
928:
924:
917:
914:
909:
905:
900:
895:
891:
887:
884:(4): 286β93.
883:
879:
875:
868:
865:
860:
856:
853:(66): 371β9.
852:
848:
841:
839:
835:
830:
826:
821:
816:
812:
808:
804:
800:
796:
792:
788:
781:
778:
772:
770:
766:
761:
757:
752:
747:
743:
739:
736:(5): 775β86.
735:
731:
727:
720:
718:
716:
712:
707:
703:
699:
695:
692:(2): 229β39.
691:
687:
680:
678:
674:
669:
665:
661:
657:
653:
649:
648:Br J Dermatol
642:
640:
636:
631:
627:
622:
617:
613:
609:
605:
601:
597:
590:
588:
584:
579:
575:
570:
565:
562:(9): 1063β6.
561:
557:
553:
546:
544:
542:
538:
533:
529:
524:
519:
515:
511:
507:
503:
499:
492:
490:
488:
484:
479:
475:
471:
467:
464:(3): 224β31.
463:
459:
451:
449:
445:
442:
437:
435:
433:
431:
429:
425:
419:
417:
415:
411:
407:
402:
393:
386:
384:
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363:
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348:
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309:
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172:
171:
167:
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158:
155:
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141:
139:
137:
133:
132:synchronously
129:
125:
121:
117:
113:
108:
106:
102:
98:
94:
91:recognizable
90:
89:cytologically
86:
82:
75:How it arises
74:
72:
70:
66:
62:
58:
54:
50:
46:
42:
38:
35:(also termed
34:
30:
21:
1586:
1582:
1556:
1552:
1522:
1518:
1511:
1471:
1467:
1457:
1430:
1426:
1416:
1389:
1385:
1375:
1350:
1346:
1340:
1315:
1311:
1305:
1280:
1276:
1269:
1247:(2): 104β7.
1244:
1240:
1233:
1196:
1192:
1148:
1144:
1137:
1112:
1108:
1071:
1067:
1057:
1046:
1030:
1005:
1001:
995:
973:(3): 391β8.
970:
966:
930:
926:
916:
881:
877:
867:
850:
846:
794:
790:
780:
733:
729:
689:
685:
651:
647:
603:
599:
559:
555:
508:(2): 38β42.
505:
501:
461:
457:
403:
399:
381:
145:
109:
93:premalignant
78:
52:
48:
44:
40:
37:field change
36:
33:field effect
32:
28:
27:
1589:(1): 9β22.
1468:Cancer Lett
1347:Hum. Pathol
269:Colorectal
253:Colorectal
237:Colorectal
221:Colorectal
205:Colorectal
189:Colorectal
173:Colorectal
116:lung cancer
1241:Oral Oncol
847:Discov Med
420:References
365:Esophagus
85:epigenetic
458:BioEssays
103:(CIS) or
97:dysplasia
1613:Category
1603:21160525
1575:16079316
1541:13094644
1498:18164807
1449:22808291
1408:23098428
1367:19695681
1332:21353335
1297:19786217
1261:21147548
1225:22494821
1199:(1): 3.
1165:20947886
1129:21706233
1090:16174854
1022:20553211
987:23142414
949:16618413
908:20443907
859:22127108
829:23539594
760:24173184
706:19685287
668:18067627
630:19462462
600:Prostate
578:22220503
532:22550239
478:21254148
371:77%-100%
349:Stomach
333:Stomach
95:foci of
1489:2744582
1440:3396065
1216:3351028
899:5407481
820:3749880
799:Bibcode
791:Science
751:3798355
621:3690597
523:5821032
374:23%-79%
1601:
1573:
1539:
1519:Cancer
1496:
1486:
1447:
1437:
1406:
1365:
1330:
1295:
1259:
1223:
1213:
1163:
1127:
1088:
1038:
1020:
985:
947:
906:
896:
857:
827:
817:
758:
748:
704:
666:
628:
618:
576:
530:
520:
476:
156:Cancer
105:cancer
61:tissue
410:ERCC1
240:ERCC1
168:Ref.
65:organ
59:at a
57:cells
1599:PMID
1571:PMID
1537:PMID
1494:PMID
1445:PMID
1404:PMID
1363:PMID
1328:PMID
1293:PMID
1257:PMID
1221:PMID
1161:PMID
1125:PMID
1086:PMID
1036:ISBN
1018:PMID
983:PMID
945:PMID
904:PMID
855:PMID
825:PMID
756:PMID
702:PMID
664:PMID
626:PMID
574:PMID
528:PMID
474:PMID
414:PMS2
406:Ku86
368:MLH1
352:MLH1
336:MGMT
320:MLH1
304:MLH1
288:MGMT
256:PMS2
243:100%
224:MSH2
208:MGMT
192:MGMT
176:MGMT
159:Gene
83:and
1591:doi
1561:doi
1527:doi
1484:PMC
1476:doi
1472:260
1435:PMC
1394:doi
1355:doi
1320:doi
1285:doi
1281:141
1249:doi
1211:PMC
1201:doi
1153:doi
1145:Gut
1117:doi
1113:396
1076:doi
1010:doi
975:doi
935:doi
931:130
894:PMC
886:doi
815:PMC
807:doi
795:339
746:PMC
738:doi
694:doi
690:118
656:doi
652:157
616:PMC
608:doi
564:doi
518:PMC
510:doi
466:doi
358:20%
355:73%
342:78%
339:88%
326:20%
323:31%
310:25%
307:33%
294:38%
291:54%
278:40%
275:55%
272:XPF
262:50%
259:88%
246:40%
227:13%
214:60%
211:70%
198:11%
195:47%
182:34%
179:46%
134:or
51:or
31:or
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