Transcriptome profiles of stem-like cells from primary breast cancers allow identification of ITGA7 as a predictive marker of chemotherapy response.

BACKGROUND: Breast cancer stem cells (BCSCs) are drivers of therapy-resistance, therefore are responsible for poor survival. Molecular signatures of BCSCs from primary cancers remain undefined. Here, we identify the consistent transcriptome of primary BCSCs shared across breast cancer subtypes, and we examine the clinical relevance of ITGA7, one of the genes differentially expressed in BCSCs. METHODS: Primary BCSCs were assessed using immunohistochemistry and fluorescently labelled using Aldefluor (n = 17). Transcriptomes of fluorescently sorted BCSCs and matched non-stem cancer cells were determined using RNA-seq (n = 6). ITGA7 expression was examined in breast cancers using immunohistochemistry (n = 305), and its functional role was tested using siRNA in breast cancer cells. RESULTS: Proportions of BCSCs varied from 0 to 9.4%. 38 genes were significantly differentially expressed in BCSCs; genes were enriched for functions in vessel morphogenesis, motility, and metabolism. ITGA7 was found to be significantly downregulated in BCSCs, and low expression significantly correlated with reduced survival in patients treated with chemotherapy, and with chemoresistance in breast cancer cells in vitro. CONCLUSIONS: This study is the first to define the molecular profile of BCSCs from a range of primary breast cancers. ITGA7 acts as a predictive marker for chemotherapy response, in accordance with its downregulation in BCSCs.

Lymphadenopathy in a series of Egyptian pediatric patients and the role of pathology in the diagnostic workup.

Assessment of lymphadenopathy in children represents a diagnostic challenge because of the extensive differential diagnoses, including reactive and malignant conditions. Knowledge of the etiologic pattern of lymphadenopathy in a given geographical region is essential for making a confident diagnosis or for suspecting a disease. Hence, the present study was carried out to identify different etiologies of lymphadenopathy in children in our region and to assess parameters commonly associated with malignancy, with an emphasis on the role of pathology. One hundred and twenty patients aged 1 month to 18 years were included in the study. They were sorted into neoplastic and nonneoplastic (infectious and noninfectious) groups. In 56 patients, biopsy (fine needle aspiration cytology [FNAC], core needle, or excision biopsy) was essential to reach the final diagnosis. Sensitivity of FNAC in the differentiation between neoplastic and nonneoplastic lymphadenopathy was 92.3%, and specificity was 90.0%, with a diagnostic accuracy of 91.3%. We concluded that malignancy should be suspected in the following conditions: presence of abdominal or multiple symptoms; symptom duration of 1-6 months; generalized lymphadenopathy; multiple groups of lymph node (LN) involved; LN size > 2 cm; amalgamated, hard, fixed, and nontender LNs; certain abnormal complete blood count findings; blast cells in blood film; and elevated lactate dehydrogenase level. In such cases, LN biopsy is highly recommended. A final diagnosis was achieved after integrating information from history and clinical findings with the laboratory, radiological, pathological, and microbiological findings. Accordingly, an algorithm for primary diagnostic evaluation of children with lymphadenopathy is suggested.

Lymphadenopathy in a Series of Egyptian Pediatric Patients and the Role of Pathology in the Diagnostic Workup.

Assessment of lymphadenopathy in children represents a diagnostic challenge because of the extensive differential diagnoses including reactive and malignant conditions. Knowledge of the etiologic pattern of lymphadenopathy in a given geographical region is essential for making a confident diagnosis or suspecting a disease. Hence, the present study was carried out to identify different etiologies of lymphadenopathy in children in our region, and assess parameters commonly associated with malignancy, with an emphasis on the role of pathology in the diagnostic workup. One hundred and twenty patients aged one month to 18 years were included in the study. They were sorted into neoplastic and non-neoplastic (Infectious and non-infectious). In only 56 patients, biopsy, whether fine needle aspiration cytology (FNAC), core needle or excision biopsy, was essential to reach the final diagnosis. Sensitivity of FNAC in the differentiation between neoplastic and non-neoplastic lymphadenopathy was 92.3%, specificity 90.0%, with a diagnostic accuracy of 91.3%. We concluded that malignancy should be suspected in the following conditions: presence of abdominal or multiple symptoms, symptoms duration of 1-6 months, generalized lymphadenopathy, multiple groups of lymph node (LN) involved, LN size > 2 cm, amalgamated, hard, fixed and non-tender LNs, certain abnormal CBC findings, blast cells in blood film and elevated LDH level. In such cases, LN biopsy is highly recommended. A final diagnosis was achieved after integrating information from history and clinical findings with those of the laboratory, radiological, pathological and microbiological findings. Accordingly, an algorithm for primary diagnostic evaluation of children with lymphadenopathy is suggested.