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Flow cytometry and quantitative immunohistochemical study of cell cycle regulation proteins in invasive breast carcinoma
Author(s) -
Michels JeanJacques,
Duigou Françoise,
Marnay Jacques,
HenryAmar Michel,
Delozier Thierry,
Denoux Yves,
Chasle Jacques
Publication year - 2003
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.11209
Subject(s) - immunohistochemistry , medicine , flow cytometry , lymph node , cell cycle , carcinoma , oncology , pathology , cyclin b1 , breast carcinoma , breast cancer , cyclin a , cyclin d1 , cancer research , cancer , cyclin dependent kinase 1 , immunology
BACKGROUND Between January 11, 1991 and January 8, 1992, 104 patients with previously untreated, invasive, primitive breast carcinoma were admitted to the authors' hospital. METHODS For each patient, flow cytometry DNA analyses on frozen samples and on immunohistochemical staining were performed, including Ki‐67, cyclin A, p53 , and p21 waf1 ( p21 ), with assessment of the percentages of positive nuclei were assessed. Correlations with classic clinicopathologic data and survival (overall, metastasis free, or recurrence free) and a multivariate analysis were performed. RESULTS After a multivariate analysis according to a Cox model that was stratified by age, tumor size, tumor grade, lymph node status, and receptor status, among the factors studied, the presence of p21 was the unique remaining prognostic factor for patients with invasive breast carcinoma. Because of the lack of a correlation between p21 and proliferative factors (Ki‐67, S‐phase, and cyclin A), the authors combined p21 with those markers and found that, for the different combinations, after statistical analysis, only p21 combined with S‐phase or with cyclin A and lymph node status were salient survival prognostic factors. CONCLUSIONS Immunohistochemical study of proteins involved in the cell cycle and assessment of proliferative activity using flow cytometric DNA analysis aided the authors in singling out correlations of cyclin A and S‐phase, along with p21 , with metastasis free survival and overall survival in patients with invasive breast carcinoma. These promising results will require confirmation in a larger series of patients. Cancer 2003;97:1376–86. © 2003 American Cancer Society. DOI 10.1002/cncr.11209