Changes in breast cancer biomarkers in the IGF1R/PI3K pathway in recurrent breast cancer after tamoxifen treatment.

Development of resistance to the antioestrogen tamoxifen occurs in a large proportion of patients with oestrogen receptor-positive (ER+) breast cancer and is an important clinical challenge. While loss of ER occurs in c.20% of tamoxifen-resistant tumours, this cannot be the sole explanation for tamoxifen treatment failure. PI3K pathway activation, including by insulin-like growth factor receptor 1 (IGF1R), has been implicated in some resistance models. The primary aim was to determine whether evidence exists in clinical breast cancer for a role of IGF1R and/or the PI3K pathway, in acquisition of resistance to tamoxifen. Invasive primary and recurrent tamoxifen-resistant tumours from the same patient (n=77) were assessed for changes in ER, progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), IGF1R, stathmin, PTEN expression and PIK3CA mutations where possible. ER and PgR levels were significantly reduced at recurrence with 22 and 45%, respectively, showing negative status at this time. Acquisition of HER2 overexpression occurred in 6% of cases. IGF1R expression was significantly reduced in both ER+ and ER- recurrences and stathmin levels increased. A positive association between stathmin and IGF1R emerged in recurrent samples, despite their opposing relationships with ER, suggesting some coalescence of their activities may be acquired. The data confirm loss of ER and PgR and gain of HER2 in some tamoxifen-resistant tumours. There is no evidence for IGF1R gain in tamoxifen resistance; increases in stathmin levels suggest that activation of the PI3K pathway may have contributed, but PTEN loss and PIK3CA hotspot mutations were relatively rare.

Splenic smooth-muscle tumors in children with acquired immunodeficiency syndrome: report of two cases of this unusual location with evidence of an association with Epstein-Barr virus.

Smooth-muscle neoplasms are rarely located in the spleen. They have been previously reported in five cases of children with human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS). Two cases of children with HIV infection/AIDS with autopsy and surgical pathology evidence of multiple smooth-muscle neoplasms with splenic involvement are presented. DNA was extracted from histology slides in both cases for analysis for Epstein Barr (EB) virus. In both cases, the presence of EB virus was confirmed. This paper documents two additional cases of the unusual phenomenon of splenic involvement by smooth-muscle neoplasms in the setting of AIDS in childhood and further supports the role of EB virus in the development of these neoplasms.

[Thymus-dependent suppression of erythroid colony formation induced by concanavalin A in the cloning of pluripotent hematopoietic stem cells of the spleen]. / Timuszavisimaia supressiia éritroidnogo kolonieobrazovaniia, indutsirovannaia konkanavalinom A, pri klonirovanii polipotentnykh stvolovykh krovetvornykh kletok selezenki.

The injection of the polyclonal activator of T-cells--concanavalin A--to normal mice is followed by a considerable decrease both in the erythroid colony-formation at the cloning of spleen CFUs, and in the number of T-cells and their helper activity in the same spleen suspensions. The suppression of erythroid colony-formation may be passively transferred by using spleen cells from mice treated with concanavalin A and irradiated lethally. Thymectomy of adult mice prevents from suppression of erythroid colony-formation induced by concanavalin A. These results suggest that the T-cells may suppress erythroid differentiation of hemopoietic stem cells.