Histological changes pertinent to local tumor progression in hereditary nonpolyposis colorectal cancer (HNPCC). A preliminary report.
While the genetic profiles of hereditary colorectal tumors are being unravelled, the mechanisms implicated in their local progression remain to be deciphered. In this work histological features occurring at the invading tumor front were investigated in ten hereditary non-polyposis colorectal cancers (HNPCC). Of eight moderately-differentiated (i.e. gland-forming) adenocarcinomas, six had dilated glands with a thin layer of tumor cells and all eight had dilated glands in which a group of cells was lacking, i.e. with a glandular pore. It was apparent that the thin glandular epithelium was a stage preceding pore formation. In glands with pores, the contents of the neoplastic glands--rich in proteolytic enzymes--were extruded directly into the extracellular matrix (ECM), leading to the local destruction of the juxtaposed matrix. It was assumed that to restore the continuity of the glands new cancer cells would grow from the tip of the free borders of the pore into the damaged ECM, thus guaranteeing a stepwise, but everlasting, tumor progression in untreated patients.
Rubio
C A
CA
Department of Pathology, Karolinska Institute and Hospital, Stockholm, Sweden. Carlos.Rubio@onkpat.ki.se
Lindblom
A
A
D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000145:classification / Q000235:genetics / Q000473:pathology*; D002352:Carrier Proteins; D002455:Cell Division / Q000502:physiology; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000145:classification / Q000235:genetics / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000235:genetics; D018450:Disease Progression; D018095:Germ-Line Mutation; D006801:Humans; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein