Tissue microarrays in non-small-cell lung cancer: reliability of immunohistochemically-determined biomarkers.
BACKGROUND
The reliability of immunohistochemically-determined biomarkers using tissue microarrays (TMAs) of clinical specimens has long been open to question. Heterogeneity related to tumor biology might compromise determination of accurate biomarker expression in tumors, especially in small core biopsies. We evaluated the reliability of immunohistochemical staining scoring in small core biopsies using 11 biomarkers in non-small-cell lung cancer (NSCLC).


METHODS
Four 1-mm tumor cores from 178 NSCLCs, 2 representing peripheral areas close to the border of normal lung tissue and 2 representing central areas, were examined. The biomarkers analyzed included p63, p40, cytokeratin 1/5/10/14, cytokeratin 7, thyroid transcription factor-1, napsin A, cyclin-D1, p53, Ki-67, integrin beta-1, and thymidylate synthase.


RESULTS
Using a random intercept logistic regression model, immunohistochemical marker expression of TMAs had a moderate to high reliability measured using the intraclass correlation coefficient (0.67-0.99) between cores within the same tumor. Reliability was dependent on the selected biomarker, with lineage-specific biomarkers being less heterogeneously expressed than functional biomarkers. Expressions of most biomarkers showed no significant difference between central versus peripheral tumor cores.


CONCLUSIONS
Our results demonstrated that biomarkers involved in clinical tumor classification (cell lineage markers) of NSCLC can be adequately assessed using 1 or 2 biopsy samples. However, the optimal number of cores required for biomarkers with functional properties varied from 1 to > 4 cores. The results indicate that the optimal number of biopsies required to compensate for potential biomarker heterogeneity should be determined individually for each biomarker used in clinical settings.
Department of Oncology, Odense University Hospital, Odense, Denmark; Institute of Clinical Research, University of Southern Denmark, Odense, Denmark. Electronic address: mette.poehl@rh.regionh.dk.
Mette
M
Pøhl
Institute of Clinical Research, University of Southern Denmark, Odense, Denmark; Department of Pathology, Odense University Hospital, Odense, Denmark.
Karen Ege
KE
Olsen
Department of Biostatistics, Institute of regional Health Research, University of Southern Denmark, Odense, Denmark.
René
R
Holst
Department of Oncology, Odense University Hospital, Odense, Denmark; Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Henrik Jørn
HJ
Ditzel
Department of Oncology, Odense University Hospital, Odense, Denmark; Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
Olfred
O
Hansen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016015:Logistic Models; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D046888:Tissue Array Analysis / Q000379:methods*
D014408:Biomarkers, Tumor
Cyclin D1; Intratumoral heterogeneity; Ki-67; Linage-specific markers; Thymidylate synthase