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Using tissue adjacent to carcinoma as a normal control: an obvious but questionable practice
Boudewijn J M Braakhuis1, C René Leemans, Ruud H Brakenhoff
1Department of Otolaryngology/Head and Neck Surgery, Vrije Universiteit Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands. bjm.braakhuis@vumc.nl
The Journal of Pathology
|May 14, 2004
Summary
Normal-appearing adjacent tissue near carcinomas may harbor genetic abnormalities. This field effect requires genetic screening of control tissues before comparing them to cancer cells.
Area of Science:
- Oncology
- Genetics
- Biochemistry
Background:
- Macroscopically normal adjacent tissue is commonly used as a control in carcinoma research.
- The assumption of genetic normality in adjacent tissues is often incorrect.
- Carcinomas can be surrounded by large fields of genetically abnormal, clonally related cells.
Purpose of the Study:
- To investigate the genetic status of macroscopically normal tissue adjacent to carcinomas.
- To determine if genetic abnormalities extend into seemingly normal epithelium surrounding tumors.
- To highlight the need for re-evaluating control tissue selection in cancer research.
Main Methods:
- Biochemical analysis of carcinoma and adjacent tissues.
- Immunohistochemical examination of tissue samples.
- Genetic techniques to assess cellular alterations.
Main Results:
- A significant proportion of carcinomas are surrounded by fields of genetically abnormal cells.
- These abnormal fields can be extensive, exceeding 7 cm in diameter.
- Cells within these fields are often clonally related to the carcinoma.
Conclusions:
- Macroscopically normal adjacent epithelium should not be assumed to be free of genetic alterations.
- Genetic screening of adjacent tissues is crucial before using them as controls for carcinoma studies.
- The field effect necessitates a re-evaluation of experimental controls in cancer research.