Survivin, a member of the inhibitory apoptosis protein family, gives rise, by an alternative splicing, to four variants with different functions. Many experimental studies indicate that p53 can regulate the expression of survivin and some of its splice variants. Although both the expression of survivin splice variants and the p53 gene were frequently altered in human cancers, nothing is known about their interactions in in vivo tumour samples. Here, we report that, in 162 breast carcinomas, p53 mutations are significantly associated with an increased expression of survivin and, in particular, its antiapoptotic splice variants (survivin-DEx3 and survivin-3B). The upregulation of these variant expressions is particularly related to p53 mutations occurring in the residues belonging to the tetramerization domain. The loss of heterozygosity in the p53 gene is also associated with an increased expression of the survivin-DEx3 variant. The expression of the proapoptotic variants (survivin-2B and survivin-2a) is not affected by any of these alterations. Our results provide for the first time in vivo evidence that, in human breast cancer, the survivin expression as well as its splicing depends on the p53 status. The results also suggest that the upregulation of antiapoptotic survivin variant expression by the mutant p53 may increase breast cancer cells survival and resistance to therapy.

Earlier age at menarche is a major risk factor for breast cancer. Our previous study identified Nrip1 (also known as Rip140) as a candidate gene for delaying female sexual maturation (FSM) and found that knocking out Nrip1 could significantly delay FSM in mice. To investigate the effects of NRIP1 in breast cancer we used human cell lines and tissue arrays along with an in vivo study of DMBA-induced carcinogenesis in Nrip1 knockout mice. Analysis of tissue arrays found that NRIP1 is elevated in tumors compared to cancer adjacent normal tissue. Interestingly, in benign tumors NRIP1 levels are higher in the cytosol of stromal cells, but NRIP1 levels are higher in the nuclei of epithelial cells in malignancies. We also found overexpression of NRIP1 in breast cancer cell lines, and that suppression of NRIP1 by siRNA in these cells significantly induced apoptosis and inhibited cell growth. Furthermore, in vivo data suggests that NRIP1 is upregulated in DMBA-induced breast cancer. Importantly, we found that DMBA-induced carcinogenesis is suppressed in Nrip1 knockdown mice. These findings suggest that NRIP1 plays a critical role in promoting the progression and development of breast cancer and that it may be a potential therapeutic target for the new breast cancer treatments.

We report on the cytopathologic findings of a Leydig cell tumor of the testis in an adult male with no evidence of endocrine dysfunction. The preoperative diagnosis was based on fine needle aspiration cytology (FNAC) and was subsequently confirmed on histomorphology. The cytologic smears were cellular and showed tumor cells arranged singly, as well as in dyscohesive clusters. The tumor cells were large, round to polygonal, with indistinct cytoplasmic margins and pale, abundant, granular to vacuolated cytoplasm. A few intranuclear Reinke's crystals that are considered pathognomonic and essential for the diagnosis were seen. The present case was of interest because of the scarcity of literature on the cytodiagnosis of this tumor. The use of FNAC for diagnosis may vitiate the need for more invasive biopsy procedures in the preoperative diagnosis of this rare testicular tumor. Diagn. Cytopathol. 2010;38:682–684. © 2009 Wiley‐Liss, Inc.

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