Same difference: A pilot study of cyclin D1, bcl-2, AMACR, and ALDH-1 identifies significant differences in expression between primary colon adenocarcinoma and its metastases.
Tumor heterogeneity implies the possibility of significantly different expression of key pathways between primary and metastatic clones. Colon adenocarcinoma is one of the few tumors where current practice includes resection of primary and isolated organ metastases simultaneously without neoadjuvant therapy. We performed a pilot study on 28 cases of colon adenocarcinoma resected simultaneously with metastases in patients with no history of neoadjuvant therapy. We assayed matched primary and metastatic tumors from each patient with common diagnostic antibodies to Bcl-2, Cyclin D1, AMACR, and ALDH-1 by immunohistochemistry with semi-quantitative interpretation on archived formalin fixed, paraffin embedded samples. We were powered for large, consistent differences between primary and metastatic expression, and found 21 of 28 had a significant difference in expression of at least one of the four proteins, accounting for multiplicity of testing. Cyclin D1 had significantly more cases with differential metastatic:primary expression than would be expected by chance alone (p-value 0.0043), favoring higher expression in the metastatic sample. Bcl-2 and ALDH-1 had trends in this direction (p-value 0.078 each). Proportionately more cases with significant differences were identified when a liver metastasis was tested. We conclude differences in expression between metastatic and primary colon adenocarcinoma within the same patient exist, and may have therapeutic and biomarker testing consequences.
Department of Pathology, Joan C Edwards School of Medicine at Marshall University, United States; Eli Lilly and Company, United States. Electronic address: goakley@marshall.edu.
Gerard J
GJ
Oakley
Department of Pathology, Joan C Edwards School of Medicine at Marshall University, United States.
Krista L
KL
Denning
Department of Pathology, Joan C Edwards School of Medicine at Marshall University, United States.
Vincent
V
Graffeo
Department of Pathology, Joan C Edwards School of Medicine at Marshall University, United States.
Doreen C
DC
Griswold
Department of Pathology, Joan C Edwards School of Medicine at Marshall University, United States.
Adam R
AR
Davis
Department of Pathology, Joan C Edwards School of Medicine at Marshall University, United States.
Linda G
LG
Brown
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000080924:Aldehyde Dehydrogenase 1 Family; D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D019938:Cyclin D1 / Q000032:analysis / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis / Q000096:biosynthesis; D009362:Neoplasm Metastasis / Q000473:pathology*; D010865:Pilot Projects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000096:biosynthesis; D019998:Racemases and Epimerases / Q000032:analysis / Q000096:biosynthesis; D050697:Retinal Dehydrogenase / Q000032:analysis / Q000096:biosynthesis; D012189:Retrospective Studies
C000595707:BCL2 protein, human; D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; D007527:Isoenzymes; D019253:Proto-Oncogene Proteins c-bcl-2; D019938:Cyclin D1; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase; D019998:Racemases and Epimerases; C108352:alpha-methylacyl-CoA racemase
Colon adenocarcinoma; CyclinD1; Immunohistochemistry; Metastasis; Tumor