[ immunohistochemical assessment of ALDH1 activity in breast cancer and it's correlation with pathologic features]

Aldehyde dehydrogenase 1 [ALDH1] is a marker of normal and malignant human mammary stem cells that has been reported to be associated with poor prognosis. Studies on the detection of ALDH1+cells can help the treatment of patients with breast cancer. The aim of this study was to determine the activity of ALDH1 in breast cancer and its relationship with the pathological features of the tumors. ALDH1 activity was studied by immunohistochemistry in 121 paraffin-embedded histological samples of breast cancer patients from Department of Pathology of Milad Hospital, Tehran, Iran during 2006-2007. The relationship of ALDH1 with the pathological features of the tumors [size, grade, lymph node metastasis and vascular invasion] was also investigated. Eighty-five percent of breast cancer samples expressed ALDH1 in their cytoplasm with a wide range of intensity [weak, moderate and strong], while 18 samples [14.9%] were completely negative. The majority of cases [97.1%] showed ALDH1 positivity in the stroma of tumors which varied from weak [2.9%] to strong [73.5%]. ALDH1 H-score [ALDH1% x intensity] of tumor cells varied from 0 to 240 [mean=80]. ALDH1 H-score was 80 in 59 [48.8%] samples. There was no statistically significant relationship between ALDH1 H-score and age [P=0.358], tumor size [P=0.375], tumor grade [P=0.207], lymph node metastasis [P=0.125] or vascular invasion [P=0.190]. ALDH1 activity was demonstrated in 85.1% of breast cancer samples although its level of expression was not correlated with the pathologic features of breast tumors

BRCA1 protein expression level and CD44[+] phenotype in breast cancer patients

CD44[+]/CD24[-/low] breast cancer cells have tumour-initiating properties with stem cell-like features. Breast cancer gene 1 [BRCA1] is a tumour suppressor gene that plays a crucial role in DNA repair and maintenance of chromosome stability. The clinicopathological features of breast cancer in BRCA1 mutation carriers suggest that BRCA1 may function as a stem-cell regulator. In the present experimental study we examined the expression and localization of the BRCA1 protein and investigated the prognostic value as well as its relationship with the putative cancer stem cell [CSC] marker [CD44] in 156 tumour samples from a well-characterized series of unselected breast carcinomas using immunohistochemistry. Statistical analysis of the data was performed using SPSS software version 16 [Chicago, IL, USA]. In breast tumours, the loss of nuclear expression was detected in 23 cases [15%], whereas cytoplasmic expression of BRCA1 was observed in 133 breast carcinomas [85%]. Altered BRCA1 expression was significantly associated with high grade and poor prognosis breast tumours [p=0.006]. We further established an inverse significant correlation between BRCA1 expression levels and CD44[+] cancer cell phenotype [p=0.02] Loss of BRCA1 expression is a marker of tumour aggressiveness and correlates with CD44[+] tumour cell phenotype. Taken together, the present study supports the idea that the loss of BRCA1 results in persistent errors in DNA replication in breast stem cells and provides targets for additional carcinogenic events