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

Immunohistochemical expression of TOP2A protein. (a) Histologically normal breast tissue from a reduction mammoplasty (RM) case featuring lack of nuclear expression of TOP2A in the epithelial cells lining a normal TDLU. (b) Histologically normal breast tissue from a patient with synchronous breast cancer showing positive nuclear staining in 4-5% of the mammary epithelial cells-higher TOP2A expression than the HNB tissues from a reduction mammoplasty case illustrated in (a). (c-d) A larger proportion of epithelial cells are immunoreactive for nuclear TOP2A protein in ductal carcinoma in situ (DCIS) and in the invasive ductal carcinoma (IDC) infiltrating the mammary fat. These cases illustrate an obvious increase in TOP2A protein expression from the lowest risk specimen from a reduction mammoplasty case (a), to the higher-risk specimens (c) and (d) (IMPOX staining for TOP2A; original magnifications 200x).
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3140260&req=5

fig9: Immunohistochemical expression of TOP2A protein. (a) Histologically normal breast tissue from a reduction mammoplasty (RM) case featuring lack of nuclear expression of TOP2A in the epithelial cells lining a normal TDLU. (b) Histologically normal breast tissue from a patient with synchronous breast cancer showing positive nuclear staining in 4-5% of the mammary epithelial cells-higher TOP2A expression than the HNB tissues from a reduction mammoplasty case illustrated in (a). (c-d) A larger proportion of epithelial cells are immunoreactive for nuclear TOP2A protein in ductal carcinoma in situ (DCIS) and in the invasive ductal carcinoma (IDC) infiltrating the mammary fat. These cases illustrate an obvious increase in TOP2A protein expression from the lowest risk specimen from a reduction mammoplasty case (a), to the higher-risk specimens (c) and (d) (IMPOX staining for TOP2A; original magnifications 200x).

Mentions: We found a striking trend toward increasing expression of TOP2A protein in this independent test set of histologically normal and benign breast tissues, ADH with or without synchronous invasive breast carcinoma, DCIS and invasive ductal breast carcinoma tissues, represented on the breast TMA. These results provide further validation of increasing expression of TOP2A protein along the histologic continuum of various breast lesions from benign to premalignant to invasive breast carcinomas it's (Figures 9(a), 9(b), 9(c), and 9(d)). For these specimen types, TOP2A protein expression data are summarized in 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)

Immunohistochemical expression of TOP2A protein. (a) Histologically normal breast tissue from a reduction mammoplasty (RM) case featuring lack of nuclear expression of TOP2A in the epithelial cells lining a normal TDLU. (b) Histologically normal breast tissue from a patient with synchronous breast cancer showing positive nuclear staining in 4-5% of the mammary epithelial cells-higher TOP2A expression than the HNB tissues from a reduction mammoplasty case illustrated in (a). (c-d) A larger proportion of epithelial cells are immunoreactive for nuclear TOP2A protein in ductal carcinoma in situ (DCIS) and in the invasive ductal carcinoma (IDC) infiltrating the mammary fat. These cases illustrate an obvious increase in TOP2A protein expression from the lowest risk specimen from a reduction mammoplasty case (a), to the higher-risk specimens (c) and (d) (IMPOX staining for TOP2A; original magnifications 200x).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig9: Immunohistochemical expression of TOP2A protein. (a) Histologically normal breast tissue from a reduction mammoplasty (RM) case featuring lack of nuclear expression of TOP2A in the epithelial cells lining a normal TDLU. (b) Histologically normal breast tissue from a patient with synchronous breast cancer showing positive nuclear staining in 4-5% of the mammary epithelial cells-higher TOP2A expression than the HNB tissues from a reduction mammoplasty case illustrated in (a). (c-d) A larger proportion of epithelial cells are immunoreactive for nuclear TOP2A protein in ductal carcinoma in situ (DCIS) and in the invasive ductal carcinoma (IDC) infiltrating the mammary fat. These cases illustrate an obvious increase in TOP2A protein expression from the lowest risk specimen from a reduction mammoplasty case (a), to the higher-risk specimens (c) and (d) (IMPOX staining for TOP2A; original magnifications 200x).
Mentions: We found a striking trend toward increasing expression of TOP2A protein in this independent test set of histologically normal and benign breast tissues, ADH with or without synchronous invasive breast carcinoma, DCIS and invasive ductal breast carcinoma tissues, represented on the breast TMA. These results provide further validation of increasing expression of TOP2A protein along the histologic continuum of various breast lesions from benign to premalignant to invasive breast carcinomas it's (Figures 9(a), 9(b), 9(c), and 9(d)). For these specimen types, TOP2A protein expression data are summarized in 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