Fox transcription factors play a critical role in the regulation of a variety of biological processes. While FoxM1 behaves like the oncogenic transcription factor, FoxO3a is known as a tumor suppressor by inhibiting FoxM1. This study aimed to investigate the clinicopathological significance of FoxM1 and FoxO3a expression in breast cancer. Expression of FoxM1 and FoxO3a were analyzed by immunohistochemical staining on tissue microarray sections from 236 breast cancer patients, and correlated with various clinicopathological characteristics. Overexpression of FoxM1 correlated with adverse clinicopathological features, such as larger tumor size, lymph node metastasis, advanced tumor stage, and lymphovascular invasion. The Kaplan-Meier survival curves revealed no prognostic significance of FoxM1 expression. However, in subgroup analyses with patients of estrogen receptor (ER) positive breast cancers, FoxM1 overexpression associated with poor disease free and overall survival. No association was found between FoxO3a and FoxM1 expression. Regarding clinicopathological variables, the only association between histologic grade and FoxO3a was observed. In conclusion, FoxM1 overexpression was significantly associated with aggressive phenotypes and poor prognosis of ER-positive breast cancer. These findings suggest the possible role of FoxM1 as a prognostic biomarker and putative target of anti-cancer therapy.
Breast Neoplasms/chemistry/mortality/*pathology ; Female ; Forkhead Transcription Factors/*analysis ; Humans ; Phenotype ; Prognosis ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/*analysis

OBJECTIVETo study the prognostic parameters in patients with breast cancer of size smaller than or equal to 2 cm which are useful for treatment and follow-up.

METHODSFour hundred and seventy-five patients with breast cancer of size smaller than or equal to 2 cm diagnosed and treated in Affiliated Union Hospital, Fujian Medical University, China during the period from January, 2002 to December, 2008 were enrolled into the study. The clinical features, pathologic findings and follow-up data were analyzed. Kaplan-Meier curve method and Cox proportional hazard regression model were used to study factors which influenced disease-free survival and overall survival of the patients.

RESULTSOnset below 40 years of age (P=0.000), presence of axillary lymph node metastasis (P=0.000) and histologic grade 3 (P=0.013) negatively correlated with 5-year disease-free survival. Onset below 40 years of age (P=0.000), presence of axillary lymph node metastasis (P=0.000), histologic grade 3 (P=0.012) and negative estrogen receptor status (P=0.035) negatively correlated with 5-year overall survival. Multivariate analysis indicated that onset below 40 years of age (HR=3.249, 95% CI: 1.514-6.974, P=0.002) and presence of axillary lymph node metastasis (HR=3.177, 95% CI: 1.695-5.953, P=0.000) were independent predictors of 5-year disease-free survival. Onset below 40 years of age (HR=5.006, 95% CI: 2.013-12.449, P=0.001), presence of axillary lymph node metastasis (HR=4.461, 95% CI: 1.948-10.218, P=0.000) and negative estrogen receptor status (HR=2.612, 95% CI: 1.092-6.246, P=0.031) were independent predictors of 5-year overall survival.

CONCLUSIONSOnset below 40 years of age, presence of axillary lymph node metastasis and negative estrogen receptor status are prognostic indicators in patients with breast cancer of size less than or equal to 2 cm. Assessment of these prognostic parameters would be helpful in treatment and follow-up of this group of breast cancer patients.

Age Factors ; Axilla ; Breast Neoplasms ; chemistry ; mortality ; pathology ; China ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Multivariate Analysis ; Prognosis ; Proportional Hazards Models ; Tumor Burden

OBJECTIVETo study the expression of phosphatase and tensin homology deleted on chromosometen ten (PTEN) protein, a tumor suppressor gene in breast cancer and its correlation with p27(kip1) and cyclin D1 expression.

METHODSPTEN protein expression, p27(kip1) and cyclin D1 protein expression were detected by immunohistochemical method in paraffin sections from 61 women with primary breast cancer. PTEN protein expression was compared with clinico-pathologic parameters as related to p27(kip1) and cyclin D1.

RESULTSPTEN, being shown in the cytoplasm, was negative in 6.6% (4/61), reduced in 41.0% (25/61) and positive in 52.5% (32/61) samples. PTEN expression level was correlated with axillary lymph node status, loss of estrogen receptor stain, recurrence and metastasis. On univariate analysis, the disease-free survival rate of patients with higher PTEN expression (> 50% cells stained) was better than those with lower expression (P = 0.0101). However, there was no correlation between p27(kip1), cyclin D1 expression or PTEN expression.

CONCLUSIONPTEN, its lower expression being correlated with poor outcome of breast cancer patients, plays a prominent role in breast cancer. p27(kip1) or cyclin D1 may not be the primary downstream genes of PTEN in breast cancer.

Adult ; Aged ; Breast Neoplasms ; chemistry ; mortality ; pathology ; Cyclin D1 ; analysis ; physiology ; Cyclin-Dependent Kinase Inhibitor p27 ; Female ; Humans ; Immunohistochemistry ; Intracellular Signaling Peptides and Proteins ; analysis ; physiology ; Lymphatic Metastasis ; Middle Aged ; PTEN Phosphohydrolase ; analysis ; physiology ; Prognosis