Alterations of p53, Bcl-2, and hMSH2 protein expression in the normal breast, benign proliferative breast disease, in situ and infiltrating ductal breast carcinomas in the upper Egypt.
BACKGROUND
Tumorigenesis involves alterations in the tumor suppressor genes (p53), protooncogenes (Bcl-2) and housekeeping genes [human MutS homologue-2 (hMSH2)]. We hypothesized that mammary carcinogenesis involves interactions among p53, Bcl-2 and hMSh2 proteins. In the Upper Egypt, the clinicopathologic features and genetic changes during mammary carcinogenesis are unknown.


METHODS
To test our hypothesis and to examine these issues, 53 mastectomy specimens, each entailing normal breast, benign proliferative breast disease (BPBD), duct carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC) were immunostained for p53, Bcl-2 and hMSH2 protein expression.


RESULTS
The average age incidence of ductal carcinomas was 43.2 +/- 7.06 years. The tumors were common in the left than right side (1.2:1, respectively, p > 0.05). Infiltrating ductal carcinoma of non-specific type was the most common histologic type. Examination of the average weighted scores in the normal breast, BPBD, DCIS and IDC, respectively, showed: (1) significant upregulation of p53 proteins (0.00 +/- 0.00, 0.00 +/- 0.00, 6.25 +/- 2.42, 6.62 +/- 2.15, p = 0.001), (2) insignificant downregulation of Bcl-2 (6.67 +/- 1.33, 5.17 +/- 2.20, 4.79 +/- 2.27 and 4.42 +/- 2.83, p = 0.37), and (3) significant downregulation of hMSH2 (11.3 +/- 0.75, 10.70 +/- 1.27, 7.11 +/- 1.50 and 7.0 +/- 1.33, p = 0.0006). There were insignificant negative correlations between p53 and both Bcl-2 (r = -0.20, p > 0.05) and hMSH2 (r = -0.15, p > 0.05) protein expression.


CONCLUSIONS
In the Upper Egypt: (1) breast cancer had similar clinicopathologic features to those in the high risk regions, and (2) alterations of the p53, Bcl-2 and hMSH2 proteins occur during mammary carcinogenesis.
Hussein
Mahmoud R
MR
Pathology Department, Faculty of Medicine, Assuit University, Assuit, Egypt. mrh17@swissinfo.org
Ismael
Howyda H
HH
D000328:Adult; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004534:Egypt; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D051718:MutS Homolog 2 Protein; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein