Prognostic significance of p53, angiogenesis, and other conventional features in operable breast cancer: subanalysis in node-positive and node-negative patients.
To validate the prognostic value of the determination of p53 expression, intratumoral microvessel density (IMD) (a measure of angiogenesis), and the conventional features, we studied 531 patients operated of breast cancer (271 node-positive and 260 node-negative), with a median follow-up exceeding 6 years. IMD was assessed by using the anti-CD31 antibody to identify the microvessels. p53, estrogen receptor (ER) and progesterone receptor (PgR) were determined by immunocytochemistry using the antibodies PAb1801, H-222 Sp2y and KD-68, respectively. The prognostic value of the markers was analyzed by univariate and multivariate statistical analyses. In the overall series p53 expression, IMD, nodal status, ER and PgR were statistically significant prognostic indicators for both relapse-free survival (RFS) and overall survival (OS) in the final multivariate model. Likewise, tumor size and menopausal status were significant prognostic indicators for RFS and OS, respectively. In the subgroup of node-negative patients who did not receive adjuvant therapy only p53, IMD, and tumor size were statistically significant in multivariate analysis. In the subgroup of node-positive patients treated with adjuvant chemotherapy, IMD, the number of involved nodes and PgR were statistically significant in multivariate analysis. In the subgroup of node-positive patients treated with adjuvant tamoxifen, IMD and ER (and the number of involved nodes, only for OS) were statistically significant for both RFS and OS in the final multivariate model. Different markers played a diverse prognostic role in the diverse subgroups studied. Angiogenesis was the sole marker which retained prognostic value in all the sub-groups analyzed. p53 retained significance only in the subgroup of node-negative patients, whilst ER and PgR were statistically significant in the subgroups of node-positive patients treated with adjuvant hormone therapy or chemotherapy, respectively.
Gasparini
G
G
Division of Medical Oncology, Ospedali Riuniti, Via Melacrino, Reggio Calabria, 89100, Italy.
Toi
M
M
Verderio
P
P
Ranieri
G
G
Dante
S
S
Bonoldi
E
E
Boracchi
P
P
Fanelli
M
M
Tominaga
T
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000098:blood supply* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008593:Menopause; D008833:Microcirculation / Q000473:pathology*; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D011237:Predictive Value of Tests; D011336:Probability; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012008:Recurrence; D015996:Survival Rate; D013629:Tamoxifen / Q000627:therapeutic use; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53; D013629:Tamoxifen