The contribution of a dysfunctional transforming growth factor-B type II receptor (TGFBRII) to prostate cancer initiation and progression was investigated in an in vivo mouse model. Transgenic mice harboring the dominantnegative mutant TGF-B type II receptor (DNTGFBRII) in mouse epithelial cell were crossed with the TRAMP prostate cancer transgenic mouse to characterize the in vivo consequences of inactivated TGF-B signaling on prostate tumor initiation and progression. Histopathologic diagnosis of prostate specimens from the TRAMP+/DNTGFBRII double transgenic mice revealed the appearance of early malignant changes and subsequently highly aggressive prostate tumors at a younger age, compared with littermates TRAMP+/Wt TGFBRII mice. Immunohistochemical and Western blotting analysis revealed significantly increased proliferative and apoptotic activities, as well as vascularity and macrophage infiltration that correlated with an elevated vascular endothelial growth factor and MCP-1 protein levels in prostates from TRAMP+/DNTGFBRII+ mice. An epithelialmesenchymal transition (EMT) effect was also detected in prostates of TRAMP+/DNTGFBRII mice, as documented by the loss of epithelial markers (E-cadherin and B-catenin) and up-regulation of mesenchymal markers (N-cadherin) and EMT-transcription factor Snail. A significant increase in the androgen receptor mRNA and protein levels was associated with the early onset of prostate tumorigenesis in TRAMP+/DNTGFBRII mice. Our results indicate that in vivo disruption of TGF-B signaling accelerates the pathologic malignant changes in the prostate by altering the kinetics of prostate growth and inducing EMT. The study also suggests that a dysfunctional TGFBRII augments androgen receptor expression and promotes inflammation in early stage tumor growth, thus conferring a significant contribution by TGF-B to prostate cancer progression.

Biofilms are colonies of bacteria or fungi that adhere to a surface, protected by an extracellular polymer matrix composed of polysaccharides and extracellular DNA. They are highly complex and dynamic multicellular structures that resist traditional means of killing planktonic bacteria. Recent developments in nanotechnology provide novel approaches to preventing and dispersing biofilm infections, which are a leading cause of morbidity and mortality. Medical device infections are responsible for approximately 60% of hospital acquired infections. In the United States, the estimated cost of caring for healthcare-associated infections is approximately between $28 billion and $45 billion per year. In this review, we will discuss our current understanding of biofilm formation and degradation, its relevance to challenges in clinical practice, and new technological developments in nanotechnology that are designed to address these challenges.

CDX-2 is a caudal-type homeobox gene, encoding a transcription factor that plays an important role in proliferation and differentiation of intestinal epithelial cells. The utility of antibodies to CDX2 in the identification of adenocarcinomas of the gastrointestinal tract, particularly colorectal adenocarcinomas, in both primary and metastatic settings is well established. It is well-known that patients with testicular tumors may occasionally lack an obvious palpable mass. However, the expression of CDX2 in malignant germ cell tumors of the testes which have metastatic potential has not been previously studied in a large series. A tissue microarray was constructed from 52 malignant germ cell tumors of the testes including: 29 cases of classic seminoma, 8 cases of embryonal carcinoma, 8 cases of yolk sac tumor, 4 cases of malignant teratoma, 2 cases of choriocarcinoma, and 1 case of spermatocytic seminoma. Ten cases of intratubular germ cell neoplasia and seven cases of benign testicles with normal seminiferous tubules were also included in tissue microarray. Immunohistochemical stains for CDX2 was performed and analyzed. Only nuclear staining was considered positive. Positive expression of CDX2 was identified in 2/2 cases (100 %) of choriocarcinoma, 4/8 cases (50 %) of teratoma, 3/8 cases (38 %) of embryonal carcinoma, 3/8 cases (38 %) of yolk sac tumor, and 1/29 cases (3 %) of classic seminoma. CDX2 was negative in all cases of intratubular germ cell neoplasia, normal seminiferous tubules, and the only case of spermatocytic seminoma. The role of CDX-2 in the differentiation of intestinal/enteric epithelial cells may contribute to the formation of trophoblastic, glandular, villous, or cystic structures in germ cell tumors of the testes. This study suggests that the expression of CDX2 in a variety of malignant germ cell tumors of the testes may be a potential pitfall in metastatic tumors of unknown primary, which are thought to be of gastrointestinal/colorectal origin but are actually from a clinically occult testicular tumor.

The therapeutic options now available for pulmonary squamous cell carcinoma (SQCC) and adenocarcinoma (ADC) are very different. The increasing demand to make a diagnosis on minimal tissue, ancillary techniques such as immunohistochemistry (IHC) are need to be highly sensitive and specific. The IHC marker p40 (ΔNp63) is a truncated isoform of p63 that is a promising IHC marker for SQCC. In this study, we have compared the specificity of p40(ΔNp63) IHC with p63 and cytokeratin 5 (CK5) on fine-needle aspiration (FNA) cell blocks (CB). Thirty cases of pulmonary SQCC and 30 cases of pulmonary ADC with CB were selected. IHC for p40(ΔNp63), p63, and CK5 were performed on all paraffin-embedded CB serial sections. All cases (n = 30) of SQCC stained positive for p40(ΔNp63). All cases of bronchopulmonary ADC were negative for both p40(ΔNp63) and CK5. Six cases (20%) of bronchopulmonary ADC demonstrated nuclear staining for p63 in at least 10% of malignant cells. Our data support p40(ΔNp63) to be more sensitive and specific and possess a greater positive and negative predictive value for SQCC in comparison to p63. This study also documents that p40(ΔNp63) does not stain ADC, which p63 does in 20% of the cases. We also found that p40(ΔNp63) shows a greater sensitivity and negative predictive value when compared to CK5. In paucicellular CB the increased indices p40(ΔNp63) provides may be extremely helpful in confirming the diagnosis of SQCC, which may have significant therapeutic implications.

There are few reported cases of cutaneous intestinal metaplasia or primary adenocarcinoma arising at the ileostomy site following panproctocolectomy. These complications have been seen almost exclusively in patients with familial adenomatous polyposis and inflammatory bowel disease (IBD). However, benign intraepidermal colonic mucosa at a reversed ileostomy site in a patient without familial adenomatous polyposis or IBD has not been documented. We report a case of a 51-year-old female with a history of colonic adenocarcinoma who presented with pruritic, erythematous, scaly plaques on the right lower abdomen, present since reversal of her ileostomy in 2007. Skin biopsy revealed benign foci of colonic epithelium with no evidence of adenomatous change. Benign intraepidermal colonic mucosa was diagnosed based on histopathologic findings and immunohistochemistry. To our knowledge, this is the first case of intraepidermal benign colonic metaplasia forming in a patient following ostomy reversal. The case emphasizes the importance of patient education and physical examination of the stoma or stoma remnants for detection of unusual or changing lesions due to the risk for malignant transformation. It also demonstrates that benign colonic mucosa should be considered in the differential diagnosis when evaluating lesions near ileostomy sites, regardless of whether the patient has a history of familial adenomatous polyposis or IBD.