Tricho-rhino-phalangeal syndrome (TRPS) is an autosomal dominant craniofacial and skeletal dysplasia that is caused by mutations involving the TRPS1 gene. Patients with TRPS have short stature, hip abnormalities, cone-shaped epiphyses and premature closure of growth plates reflecting defects in endochondral ossification. The TRPS1 gene encodes for the transcription factor TRPS1 that has been demonstrated to repress transcription in vitro. To elucidate the molecular mechanisms underlying skeletal abnormalities in TRPS, we analyzed Trps1 mutant mice (Trps1DeltaGT mice). Analyses of growth plates demonstrated delayed chondrocyte differentiation and accelerated mineralization of perichondrium in Trps1 mutant mice. These abnormalities were accompanied by increased Runx2 and Ihh expression and increased Indian hedgehog signaling. We demonstrated that Trps1 physically interacts with Runx2 and represses Runx2-mediated trans-activation. Importantly, generation of Trps1(DeltaGT/+);Runx2(+/-) double heterozygous mice rescued the opposite growth plate phenotypes of single mutants, demonstrating the genetic interaction between Trps1 and Runx2 transcription factors. Collectively, these data suggest that skeletal dysplasia in TRPS is caused by dysregulation of chondrocyte and perichondrium development partially due to loss of Trps1 repression of Runx2.

Purpose: Inflammatory breast cancer (IBC) is associated with very poor prognosis. The aims of this study are (a) to prospectively identify differential gene expression patterns associated with IBC and (b) to confirm these pathways using tissue arrays. Experimental Design: For gene expression analysis, IBC (n = 14) was clinically defined as rapidonset cancer associated with erythema and skin changes, whereas non-IBC patients (n = 20) had stage III breast cancers, and cDNA analysis was carried out using theAffymetrix (Santa Clara, CA) HG-U133A microarrays. Tissue arrays were constructed from paraffin-embedded material, and the molecular phenotype of 75 IBC was compared with results from >2,000 non-IBC.Results: Gene expression analyses indicated that IBC has higher expression of genes associated with increased metabolic rate, lipid signaling, and cell turnover relative to non-IBC tumors. Consistent with the expression analysis, IBC had statistically higher Ki-67 (93 % versus 11%; P < 0.001). BAX expression, reflecting increased apoptosis and cell turnover, was significantly uniformly higher in almost all IBC (98% versus 66%; P < 0.05), whereas the expression of Bcl-2 was not significantly different. IBC tumors were more likely to be steroid hormone receptor negative (estrogen receptor, 49% versus 30%; P = 0.002; progesterone receptor, 68% versus 42%; P = 0.001). The expression of tyrosine kinases was not significantly different. E-cadherin was found to be expressed in 87% of IBC, whereas the expression p53 was not significantly different. Conclusion:This study is one of the largest molecular analyses of IBC. Both IBC and non-IBC are genetically heterogeneous with consistent differences in the molecular phenotype of IBC.Breast cancer is complex and heterogeneous, with a range of overlapping clinical phenotypes that manifest a wide variation in prognosis and outcome. Inflammatory breast cancer (IBC) is a rare form of invasive breast cancer characterized clinically by rapid onset of breast erythema, edema, and ridging, with the time from first symptom/sign to diagnosis of V3 months (1). Until the advent of systemic therapy, this disease was almost universally fatal. Approximately 20% of patients with IBC have gross distant metastases at the time of diagnosis (2), in contrast to <5% of invasive ductal carcinomas of no special type. The mean 5-year survival rate in most studies of patients with IBC with local therapy alone is <5%, with median survival from 12 to 36 months (3). This is in contrast to no-special-type breast cancer where the 5-year survival exceeds 50% with local treatment alone. Thus, with local therapy alone, the probability of surviving IBC is only one-tenth that of other invasive breast cancers. Hence, IBC provides an ideal clinical window to study the molecular events that contribute to metastases and poor survival outcome. However, little is known about the molecular biology of this unusual and lethal variant of invasive breast cancer. There has been limited research done on the genetic alte...

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Granulomatous mastitis is a rare and benign inflammatory condition of the breast most commonly affecting women of child-bearing age as well as patients on oral contraceptives. This condition is important to identify due to its diagnostic mimicry of malicious entities such as breast carcinoma. Clinical and radiological findings are nonspecific and may overlap with breast carcinomas, thus pathologic confirmation is often necessary for definitive diagnosis. Although cases of granulomatous mastitis have been described in cisgender females, there have been no reported cases in the transgender patient, a growing patient population with few imaging guidelines. Transgender patients are at risk of developing this breast entity due to the use of long-term hormone treatments or presence of residual breast tissue. A trial of antibiotics or steroids may be administered. However, surgical treatment is often necessary in recurrent or refractory cases.

Pretreatment staging MRI can detect multicentric and/or contralateral additional tumor sites, which ultimately changes staging, treatment options, and outcomes for patients with biopsy-proven breast cancer. There is no correlation between primary breast cancer subtype and likelihood of multicentric or contralateral disease.