R. Silvestrini et al., P53 AND BCL-2 EXPRESSION CORRELATES WITH CLINICAL OUTCOME IN A SERIESOF NODE-POSITIVE BREAST-CANCER PATIENTS, Journal of clinical oncology, 14(5), 1996, pp. 1604-1610
Background and Purpose: The tumor-suppressor gene TP53 and the proto-o
ncogene bcl-2 encode, respectively, for a nuclear phosphoprotein and f
or a mitochondrial protein involved in multiple cellular functions, Th
e proteins provide prognostic information in node-negative breast canc
er and are supposed to influence treatment responsiveness. We analyzed
the predictive role of p53 and bcl-2 expression, alone and in associa
tion with other variables, in postmenopausal women with node-positive,
estrogen receptor-positive (ER+) breast cancers treated with radical
or conservative surgery plus radiotherapy and adjuvant tamoxifen for a
t least 1 year. Patients and Methods: On 240 resectable cancers, we de
termined the expression of p53 and bcl-2, using immuno-histochemistry,
cell proliferation (H-3-thymidine labeling index [H-3-dT LI]), and ER
and progesterone receptors (PgR). Results: p53 expression and 3H-dT L
I were weakly related to one another and both were unrelated to bcl-2,
Relapse-free and distant metastasis-free survival at 5 years were sig
nificantly lower for patients with tumors that highly expressed p53 (P
= .0001) and for those that weakly expressed or did not express bcl-2
(P = .02). However, p53, but not bcl-2, provided prognostic informati
on independent of tumor size, axillary node involvement, steroid recep
tors, and H-3-dT LI. Moreover, the simultaneous p53 overexpression and
lack of PgR identified patients at maximum risk of relapse, whereas b
cl-2 overexpression, associated with a low 3H-dT LI or the presence of
PgR, improved the prognostic resolution for low-risk patients. Conclu
sion: p53 expression appears to be indicative of clinical outcome in p
ostmenopausal patients treated with tamoxifen, Whether p53 overexpress
ion and weak bcl-2 expression are indicators of biologic aggressivenes
s, regardless of treatment, or of hormone resistance remains to be def
ined. (C) 1996 by American Society of Clinical Oncology.