Mean Nuclear Area and Metallothionein Expression in Ductal Breast Tumors: Correlation With Estrogen Receptor Status

Breast carcinoma is the most common malignancy in women. Estrogen is an important growth factor for breast tumor that plays an important role in regulating the proliferation and differentiation of normal and malignant mammary epithelial cells. Nuclear morphometry and metallothioneins (MTs) are indicators of proliferation that have been used as predictors of prognosis in many tumors. The present study aimed to study mean nuclear area (MNA) and MT; estrogen receptor (ER) expression in fibroadenoma (FA), ductal carcinoma in situ (DCIS), and infiltrating ductal carcinoma (IDC) of the breast. Also MNA and MT expression will be correlated with histologic grade and ER status in breast carcinoma. Breast tissues from 18 patients with FA, 10 patients with DCIS, and 40 patients with IDC were used in this study. MNA and MT expression; as proliferation markers; were investigated and correlated with ER status. All cases of FA, 7 out of 10 cases (70%) of DCIS and 23 out of 40 cases (57.5%) of IDC were positive for ER. MNA of cancer cells was significantly larger than that of normal and benign breast tissue. A significant direct correlation was found between MNA and histologic grades. MNA of ER-negative carcinomas was significantly larger than that of ER-positive tumors. In normal and benign breast tissue, myoepithelial cells consistently expressed the MT protein. Four out of 10 DCIS cases (40%) and 24 out of 40 cases of IDC cases (60%) were positively stained for MT. MT positivity was directly correlated with histologic grade of IDC. There was a highly significant inverse correlation between MT and ER overexpression. From this study, it is concluded that in invasive ductal carcinoma of the breast, the large MNA and MT overexpression are correlated with histologic grades and ER negativity. Therefore, large MNA and MT overexpression may be possible important indicators for more aggressive and less differentiated breast carcinoma.

[1]  G. Serio,et al.  Pure ductal carcinoma in situ and in situ component of ductal invasive carcinoma of the breast. A preliminary morphometric study. , 2003, Journal of experimental & clinical cancer research : CR.

[2]  M. Nadji,et al.  Localization of metallothionein in breast carcinomas. An immunohistochemical study , 2005, Virchows Archiv.

[3]  H. Zhang,et al.  Expression of metallothionein in invasive ductal breast cancer in relation to prognosis. , 2000, Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer.

[4]  S Thameem Dheen,et al.  Metallothionein 2A expression is associated with cell proliferation in breast cancer. , 2002, Carcinogenesis.

[5]  A. Douglas-Jones,et al.  The effect of fixation and processing on the sensitivity of oestrogen receptor assay by immunohistochemistry in breast carcinoma. , 2002, Journal of clinical pathology.

[6]  S. Tsujitani,et al.  Nuclear profiles of cancer cells reveal the metastatic potential of gastric cancer , 2000, The Journal of pathology.

[7]  V. Canzonieri,et al.  Defining prognostic factors in malignancies through image analysis. , 1998, European journal of cancer.

[8]  H. Bloom,et al.  Histological Grading and Prognosis in Breast Cancer , 1957, British Journal of Cancer.

[9]  J. Mullins,et al.  Immunohistochemical demonstration of metallothionein in benign and malignant canine mammary tumours. , 1999, Histology and histopathology.

[10]  P. Isaacson,et al.  Immunoproliferative small-intestinal disease. An immunohistochemical study. , 1989, The American journal of surgical pathology.

[11]  Expression of metallothionein and nuclear size in discrimination of malignancy in mucinous ovarian tumors. , 1999, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[12]  D. Lamm,et al.  Metallothionein isoform 1 and 2 gene expression in the human bladder: evidence for upregulation of MT-1X mRNA in bladder cancer. , 2001, Cancer detection and prevention.

[13]  L. Fan,et al.  Potential role of p53 on metallothionein induction in human epithelial breast cancer cells , 2002, British Journal of Cancer.

[14]  P. Tan,et al.  Significance of metallothionein expression in breast myoepithelial cells , 2001, Cell and Tissue Research.

[15]  N. Harpaz,et al.  Differential diagnosis of borderline and invasive serous cystadenocarcinomas of the ovary by computerized interactive morphometric analysis of nuclear features , 1992, Cancer.

[16]  S. Krüger,et al.  Correlation of morphometry, nucleolar organizer regions, proliferating cell nuclear antigen and Ki67 antigen expression with grading and staging in urinary bladder carcinomas. , 1995, British journal of urology.

[17]  R Nafe,et al.  Histomorphometry in paraffin sections of thyroid tumors. , 1992, Pathology, research and practice.

[18]  D. Cosgrove The breast , 1999, European Radiology.

[19]  B. Vogelstein,et al.  The relationship of quantitative nuclear morphology to molecular genetic alterations in the adenoma-carcinoma sequence of the large bowel. , 1992, The American journal of pathology.

[20]  A. Llombart‐Bosch,et al.  Benign, preinvasive and invasive ductal breast lesions. A comparative study with quantitative techniques: morphometry, image- and flow cytometry. , 1999, Pathology, research and practice.

[21]  B. Brandt,et al.  Textbook of Surgery: The Biological Basis of Modern Surgical Practice , 1987 .

[22]  P. Tan,et al.  Correlation of Nuclear Morphometry with Pathologic Parameters in Ductal Carcinoma In Situ of the Breast , 2001, Modern Pathology.

[23]  I. Barshack,et al.  Potential use of spectral image analysis for the quantitative evaluation of estrogen receptors in breast cancer. , 2000, Histology and histopathology.

[24]  F. Abdul-Karim,et al.  Ovarian hyperstimulation by LH leads to mammary gland hyperplasia and cancer predisposition in transgenic mice. , 2002, Endocrinology.

[25]  Geraint T. Williams,et al.  Clonal overexpression of metallothionein is induced by somatic mutation in morphologically normal colonic mucosa , 1998, The Journal of pathology.

[26]  M. Zabel,et al.  Steroid receptor status, proliferation and metallothionein expression in primary invasive ductal breast cancers , 2009, Pathology Oncology Research.

[27]  T. Nakajima,et al.  Immunohistochemical expression of metallothionein in invasive breast cancer in relation to proliferative activity, histology and prognosis. , 1996, Oncology.