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Bcl‐2 with loss of apoptosis allows accumulation of genetic alterations: A pathway to metastatic progression in human breast cancer
Author(s) -
Sierra Angels,
Castellsagué Xavier,
Escobedo Agustín,
Lloveras Belen,
GarcíaRamirez Marta,
Moreno Abelardo,
Fabra Angels
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(20000320)89:2<142::aid-ijc7>3.0.co;2-b
Subject(s) - oncogene , breast cancer , lymph node , apoptosis , cancer , cancer research , metastasis , immunohistochemistry , ductal carcinoma , breast carcinoma , molecular medicine , biology , mammary gland , pathology , medicine , oncology , cell cycle , biochemistry
We have examined whether the extended life span of cells induced by Bcl‐2 in T 1 ductal breast carcinomas might favor the acquisition and accumulation of genetic alterations that induce lymph node metastases. We analyzed the expression of c‐Myc, c‐erbB‐2 and epidermal growth factor receptor by immuno‐histochemistry in a group of 142 T 1 (<2 cm) ductal breast carcinomas embedded in paraffin, previously studied for p53 mutation and Bcl‐2 over‐expression. We also measured the apoptotic status and estimated the excess risk (pOR) for lymph node metastasis according to the number of accumulated oncogene alterations and Bcl‐2 and p53 expression. The linear relationship between number of oncogene alterations and presence of lymph node metastasis was statistically significant in Bcl‐2‐positive tumors (trend test, p = 0.03), p53 ‐mutated tumors (trend test, p = 0.08) and tumors with loss of apoptosis (trend test, p = 0.08). Very large associations (pOR > 12) between the number of oncogene alterations and lymph node metastasis were observed among Bcl‐2‐positive tumors that showed increased loss of apoptosis (trend test, p = 0.03). Furthermore, in p53‐negative tumors, a strong linear association was found between the number of oncogene alterations and risk of lymph node metastasis among Bcl‐2‐positive tumors (trend test, p = 0.03). In human T 1 ductal breast carcinoma, over‐expression of Bcl‐2 along with loss of apoptosis might render breast cancer cells susceptible to the acquisition of additional genetic lesions related to disease progression among p53‐negative tumors. Thus, in breast cancer, there are at least 2 pathways to progression: Bcl‐2‐ and p53‐dependent mechanisms. Int. J. Cancer (Pred. Oncol.) 89:142–147, 2000. © 2000 Wiley‐Liss, Inc.