TY - JOUR
T1 - Differentiation of Lobular versus Ductal Breast Carcinomas by Expression Microarray Analysis
AU - Korkola, James E.
AU - DeVries, Sandy
AU - Fridlyand, Jane
AU - Hwang, E. Shelley
AU - Estep, Anne L.H.
AU - Chen, Yunn Yi
AU - Chew, Karen L.
AU - Dairkee, Shanaz H.
AU - Jensen, Ronald M.
AU - Waldman, Frederic M.
PY - 2003/11/1
Y1 - 2003/11/1
N2 - Invasive lobular and ductal breast tumors have distinct histologies and clinical presentation. Other than altered expression of E-cadherin, little is known about the underlying biology that distinguishes the tumor subtypes. We used cDNA microarrays to identify genes differentially expressed between lobular and ductal tumors. Unsupervised clustering of tumors failed to distinguish between the two subtypes. Prediction analysis for microarrays (PAM) was able to predict tumor type with an accuracy of 93.7%. Genes that were significantly differentially expressed between the two groups were identified by MaxT permutation analysis using t tests (20 cDNA clones and 10 unique genes), significance analysis for microarrays (33 cDNA clones and 15 genes, at an estimated false discovery rate of 2%), and PAM (31 cDNAs and 15 genes). There were 8 genes identified by all three of these related methods (E-cadherin, survivin, cathepsin B, TPI1, SPRY1, SCYA14, TFAP2B, and thrombospondin 4), and an additional 3 that were identified by significance analysis for microarrays and PAM (osteopontin, HLA-G, and CHC1). To validate the differential expression of these genes, 7 of them were tested by real-time quantitative PCR, which verified that they were differentially expressed in lobular versus ductal tumors. In conclusion, specific changes in gene expression distinguish lobular from ductal breast carcinomas. These genes may be important in understanding the basis of phenotypic differences among breast cancers.
AB - Invasive lobular and ductal breast tumors have distinct histologies and clinical presentation. Other than altered expression of E-cadherin, little is known about the underlying biology that distinguishes the tumor subtypes. We used cDNA microarrays to identify genes differentially expressed between lobular and ductal tumors. Unsupervised clustering of tumors failed to distinguish between the two subtypes. Prediction analysis for microarrays (PAM) was able to predict tumor type with an accuracy of 93.7%. Genes that were significantly differentially expressed between the two groups were identified by MaxT permutation analysis using t tests (20 cDNA clones and 10 unique genes), significance analysis for microarrays (33 cDNA clones and 15 genes, at an estimated false discovery rate of 2%), and PAM (31 cDNAs and 15 genes). There were 8 genes identified by all three of these related methods (E-cadherin, survivin, cathepsin B, TPI1, SPRY1, SCYA14, TFAP2B, and thrombospondin 4), and an additional 3 that were identified by significance analysis for microarrays and PAM (osteopontin, HLA-G, and CHC1). To validate the differential expression of these genes, 7 of them were tested by real-time quantitative PCR, which verified that they were differentially expressed in lobular versus ductal tumors. In conclusion, specific changes in gene expression distinguish lobular from ductal breast carcinomas. These genes may be important in understanding the basis of phenotypic differences among breast cancers.
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M3 - Article
C2 - 14612510
AN - SCOPUS:10744226188
SN - 0008-5472
VL - 63
SP - 7167
EP - 7175
JO - Cancer Research
JF - Cancer Research
IS - 21
ER -