Limits...
Novel molecular markers of malignancy in histologically normal and benign breast.

Nasir A, Chen DT, Gruidl M, Henderson-Jackson EB, Venkataramu C, McCarthy SM, McBride HL, Harris E, Khakpour N, Yeatman TJ - Patholog Res Int (2011)

Bottom Line: We also demonstrated an increasing expression of TOP2A protein on an independent test set of HNB/benign/reductionmammoplasties, atypical-ductal-hyperplasia with and without synchronous breast cancer, DCIS and IDC tissues using a custom tissue microarray (TMA).In conclusion, TOP2A, MCM2, and BUB1B proteins are potential molecular biomarkers of malignancy in histologically normal and benign breast tissues.Larger-scale clinical validation studies are needed to further evaluate the clinical utility of these molecular biomarkers.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomic Pathology, Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.

ABSTRACT
To detect the molecular changes of malignancy in histologically normal breast (HNB) tissues, we recently developed a novel 117-gene-malignancy-signature. Here we report validation of our leading malignancy-risk-genes, topoisomerase-2-alpha (TOP2A), minichromosome-maintenance-protein-2 (MCM2) and "budding-uninhibited-by-benzimidazoles-1-homolog-beta" (BUB1B) at the protein level. Using our 117-gene malignancy-signature, we classified 18 fresh-frozen HNB tissues from 18 adult female breast cancer patients into HNB-tissues with low-grade (HNB-LGMA; N = 9) and high-grade molecular abnormality (HNB-HGMA; N = 9). Archival sections of additional HNB tissues from these patients, and invasive ductal carcinoma (IDC) tissues from six other patients were immunostained for these biomarkers. TOP2A/MCM2 expression was assessed as staining index (%) and BUB1B expression as H-scores (0-300). Increasing TOP2A, MCM2, and BUB1B protein expression from HNB-LGMA to HNB-HGMA tissues to IDCs validated our microarray-based molecular classification of HNB tissues by immunohistochemistry. We also demonstrated an increasing expression of TOP2A protein on an independent test set of HNB/benign/reductionmammoplasties, atypical-ductal-hyperplasia with and without synchronous breast cancer, DCIS and IDC tissues using a custom tissue microarray (TMA). In conclusion, TOP2A, MCM2, and BUB1B proteins are potential molecular biomarkers of malignancy in histologically normal and benign breast tissues. Larger-scale clinical validation studies are needed to further evaluate the clinical utility of these molecular biomarkers.

No MeSH data available.


Related in: MedlinePlus

Mean TOP2A index in independent test sets of histologically normal breast (including reduction mammoplasty tissues), histologically normal and benign breast tissues from patients without and with synchronous cancer, DCIS and invasive breast carcinoma tissues. There is an obvious trend toward increasing TOP2A expression from benign to malignant breast tissues.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3140260&req=5

fig10: Mean TOP2A index in independent test sets of histologically normal breast (including reduction mammoplasty tissues), histologically normal and benign breast tissues from patients without and with synchronous cancer, DCIS and invasive breast carcinoma tissues. There is an obvious trend toward increasing TOP2A expression from benign to malignant breast tissues.

Mentions: Apart from cross-platform validation of 3 of our leading malignancy genes in archival HNB tissue samples, we further demonstrated the differential expression of TOP2A protein on independent test sets of Histologically normal breast tissues, including reduction mammoplasty samples, benign breast tissue from patients with and without synchronous breast cancer, and a set of DCIS and invasive breast carcinomas in a custom-designed breast TMA (Figure 10).


Novel molecular markers of malignancy in histologically normal and benign breast.

Nasir A, Chen DT, Gruidl M, Henderson-Jackson EB, Venkataramu C, McCarthy SM, McBride HL, Harris E, Khakpour N, Yeatman TJ - Patholog Res Int (2011)

Mean TOP2A index in independent test sets of histologically normal breast (including reduction mammoplasty tissues), histologically normal and benign breast tissues from patients without and with synchronous cancer, DCIS and invasive breast carcinoma tissues. There is an obvious trend toward increasing TOP2A expression from benign to malignant breast tissues.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3140260&req=5

fig10: Mean TOP2A index in independent test sets of histologically normal breast (including reduction mammoplasty tissues), histologically normal and benign breast tissues from patients without and with synchronous cancer, DCIS and invasive breast carcinoma tissues. There is an obvious trend toward increasing TOP2A expression from benign to malignant breast tissues.
Mentions: Apart from cross-platform validation of 3 of our leading malignancy genes in archival HNB tissue samples, we further demonstrated the differential expression of TOP2A protein on independent test sets of Histologically normal breast tissues, including reduction mammoplasty samples, benign breast tissue from patients with and without synchronous breast cancer, and a set of DCIS and invasive breast carcinomas in a custom-designed breast TMA (Figure 10).

Bottom Line: We also demonstrated an increasing expression of TOP2A protein on an independent test set of HNB/benign/reductionmammoplasties, atypical-ductal-hyperplasia with and without synchronous breast cancer, DCIS and IDC tissues using a custom tissue microarray (TMA).In conclusion, TOP2A, MCM2, and BUB1B proteins are potential molecular biomarkers of malignancy in histologically normal and benign breast tissues.Larger-scale clinical validation studies are needed to further evaluate the clinical utility of these molecular biomarkers.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomic Pathology, Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.

ABSTRACT
To detect the molecular changes of malignancy in histologically normal breast (HNB) tissues, we recently developed a novel 117-gene-malignancy-signature. Here we report validation of our leading malignancy-risk-genes, topoisomerase-2-alpha (TOP2A), minichromosome-maintenance-protein-2 (MCM2) and "budding-uninhibited-by-benzimidazoles-1-homolog-beta" (BUB1B) at the protein level. Using our 117-gene malignancy-signature, we classified 18 fresh-frozen HNB tissues from 18 adult female breast cancer patients into HNB-tissues with low-grade (HNB-LGMA; N = 9) and high-grade molecular abnormality (HNB-HGMA; N = 9). Archival sections of additional HNB tissues from these patients, and invasive ductal carcinoma (IDC) tissues from six other patients were immunostained for these biomarkers. TOP2A/MCM2 expression was assessed as staining index (%) and BUB1B expression as H-scores (0-300). Increasing TOP2A, MCM2, and BUB1B protein expression from HNB-LGMA to HNB-HGMA tissues to IDCs validated our microarray-based molecular classification of HNB tissues by immunohistochemistry. We also demonstrated an increasing expression of TOP2A protein on an independent test set of HNB/benign/reductionmammoplasties, atypical-ductal-hyperplasia with and without synchronous breast cancer, DCIS and IDC tissues using a custom tissue microarray (TMA). In conclusion, TOP2A, MCM2, and BUB1B proteins are potential molecular biomarkers of malignancy in histologically normal and benign breast tissues. Larger-scale clinical validation studies are needed to further evaluate the clinical utility of these molecular biomarkers.

No MeSH data available.


Related in: MedlinePlus