Breast carcinogenesis. Transition from hyperplasia to invasive lesions.
OBJECTIVE
To examine the balance loss between proliferation and apoptosis that play a role in breast cancer development, and to explore the places of various genes and molecules within this process in this supposed multistep process.


METHODS
We obtained the specimens from 40 patients between 2002 and 2004 at the Department of Pathology, Medical Faculty, Adnan Menderes University, Aydin, Turkey. We categorized the lesions ductal hyperplasia (DH), atypical ductal hyperplasia (ADH), in situ ductal carcinoma (DCIS), and invasive ductal carcinoma (IDC). We determined the tumor size, histological grade and lymph node status of invasive cases and we used nottingham prognostic index (NPI). We applied ER, PR, c-erbB2, p53, Ki-67, bcl-2, dUTP nick end labeling (TUNEL), breast cancer gene-1, matrix metalloproteinases-1 and tissue inhibitor matrix metalloproteinases-1 stains to each lesion using the immunohistochemical method.


RESULTS
We observed that ER and PR decreased in ADH when compared with DH (p=0.0001 and p=0.019). However, we determined that in DCIS as c-erbB2 (p=0.005) and Ki-67 (p=0.004) increase, TUNEL (p=0.04) and bcl-2 (p=0.005) decrease, when compared with ADH. When compared with DCIS lesions, we observed the existence of a higher c-erbB2 (p=0.003) and a lower TUNEL (p=0.012) in invasive tumors. Furthermore, we found that there is a higher MMP-1 (p=0.04) in invasive lesions, when compared with non-invasive lesions. We detected higher PR (p=0.049), lower TUNEL and c-erbB2 (p=0.017) in low grade group of NPI, when compared with high grade group of NPI.


CONCLUSIONS
As a result, it has been shown that together with increase in proliferation, decrease in apoptosis, too, contributes to the proliferation/apoptosis imbalance that occurs in breast carcinogenesis. Increase in proliferation and decrease in apoptosis are parallel with the progression of lesions. We also showed that the changes, beginning with loss of ER and PR in ADH step, can cause malign transformation, which is especially notable both in DCIS step due to Ki-67 and c-erbB2 increase, and also with bcl-2 and TUNEL decrease.
Meteoglu
Ibrahim
I
Department of Pathology, Adnan Menderes University, Medical School, Aydin 09100, Turkey. imete69@hotmail.com
Dikicioglu
Emel
E
Erkus
Muhan
M
Culhaci
Nil
N
Kacar
Furuzan
F
Ozkara
Esra
E
Uyar
Meral
M
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology; D001707:Biopsy, Needle; D001940:Breast / Q000473:pathology*; D001943:Breast Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D018270:Carcinoma, Ductal, Breast / Q000473:pathology / Q000503:physiopathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000473:pathology / Q000503:physiopathology; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009367:Neoplasm Staging; D011336:Probability; D012494:Sampling Studies; D018709:Statistics, Nonparametric; D046509:Tissue Culture Techniques