Macrophage infiltrate and prognosis in c-erbB-2-overexpressing breast carcinomas.
OBJECTIVE
Experiments were designed to investigate the association between tumor leukocytic infiltrates with other pathologic and biologic variables in primary tumors and with prognosis, and to define the phenotype of the infiltrating leukocytes.


METHODS
A retrospective series of 1,207 primary breast carcinomas was studied according to different prognostic variables, including the presence of lymphoplasmacytic infiltrate (LPI). LPI was analyzed in association with other variables and survival. Additionally, a small prospective series of surgical specimens from 75 primary breast carcinomas with infiltrating leukocytes was tested by immunohistochemistry on frozen sections to phenotypically characterize the infiltrate, using anti-CD reagents, and the tumor, using anti-c-erbB-2 oncoprotein monoclonal antibody.


RESULTS
In the retrospective series, menopausal status, nodal status, tumor size, stage, grade, and p185HER2 overexpression but not LPI were found to be associated with prognosis and maintained their prognostic significance in a multivariate analysis. LPI was significantly associated with some of these independent prognostic factors, such as tumor size (P = .03), stage (P = .004), grade III carcinomas (P < .000001), and overexpression of the p185HER2 (P < .000001). In some subgroups of patients in whom LPI was found more frequently, such as grade III cases or N- and c-erbB-2-positive cases, LPI was found to be indicative of a good prognosis (P = .008 and P = .03, respectively). Phenotypic analysis of the infiltrating leukocytes revealed a preponderance of macrophages in high-grade (P = .05) or c-erbB-2-positive (P = .008) tumors, whereas T cells constituted most of the infiltrate in the other tumors.


CONCLUSIONS
Our data demonstrate different leukocytic types in the infiltrate of breast tumors with different prognostic significance.
Pupa
S M
SM
Division of Experimental Oncology E, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Bufalino
R
R
Invernizzi
A M
AM
Andreola
S
S
Rilke
F
F
Lombardi
L
L
Colnaghi
M I
MI
Ménard
S
S
D015703:Antigens, CD / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D018275:Carcinoma, Lobular / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016130:Immunophenotyping; D016131:Lymphocyte Subsets / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology*; D008264:Macrophages / Q000473:pathology; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000473:pathology
D015703:Antigens, CD; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases