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Tom · 07-12-2006, 08:40 AM

I found this article from Penn's Oncolink fascinating, and really not unexpected. I guess I never trusted microscopically visible margins to begin with. Now it seems there are secondary "margins" of a very different nature.

http://www.oncolink.com/resources/article.cfm?c=3&s=8&ss=23&Year=2006&Month=07&id=13 317

Genomic instability in normal breast tissue may alter treatment
Megan Rauscher
Reuters Health
Posting Date: July 11, 2006

Last Updated: 2006-07-11 15:30:45 -0400 (Reuters Health)

NEW YORK (Reuters Health) - An analysis of breast tissue adjacent to tumors shows that genomic instability, a prerequisite of virtually all tumors, occurs in fields of histologically normal tissues outside the tumor margins.

This supports the concepts of "field cancerization," or a "cancer field effect," Dr. Jeffrey K. Griffith told Reuters Health. These concepts were introduced to describe "areas within tissues consisting of histologically normal, yet genetically aberrant, cells that represent fertile grounds for tumorigenesis," he and his colleagues explain in the July 1st International Journal of Cancer.

The research team, from the University of New Mexico School of Medicine in Albuquerque, used two validated markers of genomic instability -- telomere DNA content and allelic imbalance -- to define the extent and spatial distribution of genomic instability in two independent cohorts of breast tumors and their matched histologically normal adjacent tissues.

Shortened telomeres (to a level outside the range seen in > 95% of all normal tissues) and unbalanced allelic loci were present in tumor tissue as well as in 50% to 75% of tumor-adjacent, histologically normal tissue specimens at distances at least one centimeter from visible tumor margins.

"Although the extent of these genetic changes decreases as a function of the distance from the visible tumor margin, unbalanced loci are conserved between the surrounding tissues and the tumors, implying cellular clonal evolution," the authors note.

Dr. Griffith said there are two important implications of this study. The first concerns assessment of surgical tumor margins, which are conventionally defined by histological criteria.

"Since histologically normal, yet genetically aberrant, cells might represent the source of local and/or distant recurrent disease, they should be identified and removed," he told Reuters Health. "Thus, the evaluation of tumor margins should include molecular, in addition to histological, criteria."

The second implication involves risk assessment and cancer prevention. "We hypothesize that the development of the field of genetically aberrant cells is an early step in cancer progression," Dr. Griffith said. "If so, biomarkers that detect the field prior to the development of frank cancer could potentially identify women at early stages of cancer progression," he added.

Int J Cancer 2006;119:108-116.

07-12-2006, 08:40 AM	#1
Tom Senior Member Join Date: Sep 2005 Posts: 290	"Hidden margins"...This explains a lot I found this article from Penn's Oncolink fascinating, and really not unexpected. I guess I never trusted microscopically visible margins to begin with. Now it seems there are secondary "margins" of a very different nature. http://www.oncolink.com/resources/article.cfm?c=3&s=8&ss=23&Year=2006&Month=07&id=13 317 Genomic instability in normal breast tissue may alter treatment Megan Rauscher Reuters Health Posting Date: July 11, 2006 Last Updated: 2006-07-11 15:30:45 -0400 (Reuters Health) NEW YORK (Reuters Health) - An analysis of breast tissue adjacent to tumors shows that genomic instability, a prerequisite of virtually all tumors, occurs in fields of histologically normal tissues outside the tumor margins. This supports the concepts of "field cancerization," or a "cancer field effect," Dr. Jeffrey K. Griffith told Reuters Health. These concepts were introduced to describe "areas within tissues consisting of histologically normal, yet genetically aberrant, cells that represent fertile grounds for tumorigenesis," he and his colleagues explain in the July 1st International Journal of Cancer. The research team, from the University of New Mexico School of Medicine in Albuquerque, used two validated markers of genomic instability -- telomere DNA content and allelic imbalance -- to define the extent and spatial distribution of genomic instability in two independent cohorts of breast tumors and their matched histologically normal adjacent tissues. Shortened telomeres (to a level outside the range seen in > 95% of all normal tissues) and unbalanced allelic loci were present in tumor tissue as well as in 50% to 75% of tumor-adjacent, histologically normal tissue specimens at distances at least one centimeter from visible tumor margins. "Although the extent of these genetic changes decreases as a function of the distance from the visible tumor margin, unbalanced loci are conserved between the surrounding tissues and the tumors, implying cellular clonal evolution," the authors note. Dr. Griffith said there are two important implications of this study. The first concerns assessment of surgical tumor margins, which are conventionally defined by histological criteria. "Since histologically normal, yet genetically aberrant, cells might represent the source of local and/or distant recurrent disease, they should be identified and removed," he told Reuters Health. "Thus, the evaluation of tumor margins should include molecular, in addition to histological, criteria." The second implication involves risk assessment and cancer prevention. "We hypothesize that the development of the field of genetically aberrant cells is an early step in cancer progression," Dr. Griffith said. "If so, biomarkers that detect the field prior to the development of frank cancer could potentially identify women at early stages of cancer progression," he added. Int J Cancer 2006;119:108-116.