Cell-cycle-associated markers and clinical outcome in human epithelial cancers: a tissue microarray study.
The development and progression of epithelial cancers are the result of an imbalance in signals promoting and inhibiting cellular proliferation and apoptosis. The aim of this study is to evaluate the expression of cell-cycle and apoptosis regulators and correlate them with clinical outcome in the most frequent carcinomas, in order to establish common prognostic biomarkers independent of cancer origin. Using tissue microarrays (TMAs), we have analysed the immuno-expression of Ki-67, Bcl-2, Bax, cyclin D1, cyclin D3, CDK1, CDK2, CDK6, p16, p21, and p27 in a series of 205 carcinomas of the large bowel, breast, lung and prostate (80, 73, 37 and 15 cases, respectively). By univariate analysis, positivity for p27, p16 and Bcl-2 was associated with better overall survival (P<0.0135, P<0.0442 and P<0.0001, respectively). The risk of mortality was 2.3-fold greater in patients without Bcl-2 expression. TMA immunohistochemical analysis identified a subset of epithelial cancers with overlapping alterations in cell-cycle checkpoints, apoptosis regulators and tumour suppressor pathways. We found that in most common epithelial cancers, regardless of origin, Bcl-2 appears to be the key biological factor influencing clinical behaviour.
Abdulkader
I
I
Department of Pathology, School of Medicine, Clinical University Hospital, 15706 Santiago de Compostela, Spain. ihab.abdulkader.nallib@sergas.es
Sánchez
L
L
Cameselle-Teijeiro
J
J
Gude
F
F
Chávez
J E
JE
López-López
R
R
Forteza
J
J
Fraga
M
M
D000328:Adult; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000032:analysis*; D019938:Cyclin D1 / Q000032:analysis; D056743:Cyclin D3; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000032:analysis; D018844:Cyclin-Dependent Kinases / Q000032:analysis; D016213:Cyclins / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007414:Intestinal Neoplasms / Q000378:metabolism / Q000473:pathology; D019394:Ki-67 Antigen / Q000032:analysis; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D016019:Survival Analysis; D046888:Tissue Array Analysis; D051028:bcl-2-Associated X Protein / Q000032:analysis
C494826:BAX protein, human; D014408:Biomarkers, Tumor; C534696:CCND3 protein, human; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D056743:Cyclin D3; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases