The CD117 immunohistochemistry tissue microarray survey for quality assurance and interlaboratory comparison: a College of American Pathologists Cell Markers Committee Study.
BACKGROUND
We have developed tissue microarray-based surveys to allow laboratories to compare their performance in staining predictive immunohistochemical markers, including proto-oncogene CD117 (c-kit), which is characteristically expressed in gastrointestinal stromal tumors (GISTs). GISTs exhibit activating mutations in the c-kit proto-oncogene, which render them amenable to treatment with imatinib mesylate. Consequently, correct identification of c-Kit expression is important for the diagnosis and treatment of GISTs.


OBJECTIVE
To analyze CD117 immunohistochemical staining performance by a large number of clinical laboratories.


METHODS
A mechanical device was used to construct tissue microarrays consisting of 3 x 1-mm cores of 10 tumor samples, which can be used to generate hundreds of tissue sections from the arrayed cases, suitable for large-scale interlaboratory comparison of immunohistochemical staining.


RESULTS
An initial survey of 63 laboratories and a second survey of 90 laboratories, performed in 2004 and 2005, exhibited >81% concordance for 7 of 10 cores, including all 4 GIST cases, which were immunoreactive for CD117 with >95% staining concordance. Three of the cores achieved less than 81% concordance of results, possibly due to the presence of foci of necrosis in one core and CD117-positive mast cells in 2 cores of CD117-negative neoplasms.


CONCLUSIONS
There was good performance among a large number of laboratories performing CD117 immunohistochemical staining, with consistently higher concordance of results for CD117-positive GIST cases than for nonimmunoreactive cases. Tissue microarrays for CD117 and other predictive markers should be useful for interlaboratory comparisons, quality assurance, and education of participants regarding staining nuances such as the expression of CKIT by nonneoplastic mast cells.
Dorfman
David M
DM
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. ddorfman@partners.org
Bui
Marilyn M
MM
Tubbs
Raymond R
RR
Hsi
Eric D
ED
Fitzgibbons
Patrick L
PL
Linden
Michael D
MD
Rickert
Robert R
RR
Roche
Patrick C
PC
D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D019411:Clinical Laboratory Techniques / Q000592:standards; D003625:Data Collection; D005770:Gastrointestinal Neoplasms / Q000737:chemistry / Q000175:diagnosis / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000592:standards*; D007753:Laboratories / Q000592:standards*; D009656:North America; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis / Q000378:metabolism*; D011785:Quality Assurance, Health Care; D012955:Societies, Medical; D046888:Tissue Array Analysis / Q000379:methods / Q000592:standards*
D014408:Biomarkers, Tumor; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit