Overexpression of a novel cell cycle regulator ecdysoneless in breast cancer: a marker of poor prognosis in HER2/neu-overexpressing breast cancer patients.

Uncontrolled proliferation is one of the hallmarks of breast cancer. We have previously identified the human Ecd protein (human ortholog of Drosophila Ecdysoneless, hereafter called Ecd) as a novel promoter of mammalian cell cycle progression, a function related to its ability to remove the repressive effects of Rb-family tumor suppressors on E2F transcription factors. Given the frequent dysregulation of cell cycle regulatory components in human cancer, we used immunohistochemistry of paraffin-embedded tissues to examine Ecd expression in normal breast tissue versus tissues representing increasing breast cancer progression. Initial studies of a smaller cohort without outcomes information showed that Ecd expression was barely detectable in normal breast tissue and in hyperplasia of breast, but high levels of Ecd were detected in benign breast hyperplasia, ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDCs) of the breast. In this cohort of 104 IDC patients, Ecd expression levels showed a positive correlation with higher grade (P=0.04). Further analyses of Ecd expression using a larger, independent cohort (954) confirmed these results, with a strong positive correlation of elevated Ecd expression with higher histological grade (P=0.013), mitotic index (P=0.032), and Nottingham Prognostic Index score (P=0.014). Ecd expression was positively associated with HER2/neu (P=0.002) overexpression, a known marker of poor prognosis in breast cancer. Significantly, increased Ecd expression showed a strong positive association with shorter breast cancer specific survival (BCSS) (P=0.008) and disease-free survival (DFS) (P=0.003) in HER2/neu overexpressing patients. Taken together, our results reveal Ecd as a novel marker for breast cancer progression and show that levels of Ecd expression predict poorer survival in Her2/neu overexpressing breast cancer patients.

P-selectin expression in cold preserved kidneys in University of Wisconsin and histidine-tryptophan-ketoglutarate solutions.

The differences and efficacy of standard preservation solutions in kidney transplantation, University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK), remain a topic of debate in recent clinical studies. P-selectins represent glycoproteins expressed on endothelial cells and platelets responsible for the earliest events in ischemia/reperfusion injury in kidney transplantation. This study aimed to compare the levels of P-selectin expression between cold preserved kidney tissues in UW and HTK solutions. Thirty kidneys were procured from male Lewis rats and stored in cold (4°C) solutions for periods of 4, 12, 16, 20, and 24h. Group 1 (n=15) kidneys were stored in UW solutions, and group 2 (n=15) kidneys were submerged in HTK solutions. At the end of each time point, the kidneys underwent preparation and levels of P-selectin expression in the tissues were measured using Immunoblot analyses and adjusted volumetric quantification of Western blot signals. For all periods of cold preservation, P-selectin expression was significantly down-regulated in kidney tissues stored in UW compared with HTK solutions (P<0.001). In summary, UW demonstrated a significant benefit over HTK solution in down-regulating P-selectin expression in cold preserved kidney grafts.

Colonic large cell neuroendocrine carcinoma obscured by an initial diagnosis of diverticulitis.

Large cell neuroendocrine carcinomas are rare and aggressive colorectal malignancies that have a dismal prognosis. We present the following case of a patient who presented with signs and symptoms of diverticulitis. After failure of medical management, surgical intervention revealed a poorly differentiated adenocarcinoma with a component of large cell neuroendocrine carcinoma.

DCLK1 immunoreactivity in colorectal neoplasia.

INTRODUCTION: Microtubule-associated doublecortin and CaM kinase-like-1 (DCLK1) is a novel candidate marker for intestinal stem cells. The aim of our study was to assess DCLK1 immunoreactivity in colorectal carcinogenesis and its correlation with prognosis. METHODS: DCLK1 immunostaining was performed in colorectal tissue from 71 patients, including 18 adenomatous polyps, 40 primary adenocarcinomas, and 14 metastatic lesions. Each case was evaluated by a combined scoring method based on the intensity of staining (score 0-3) and the percentage of tissue staining positive (score 0-3). Immunoexpression for DCLK1 was considered as positive when the combined score was 2-6 and negative with a score of 0-1. RESULTS: Overall, 14/18 (78%) of polyps, 30/40 (75%) of primary adenocarcinomas, and 7/14 (50%) of distant metastases were positive for DCLK1. In adenomatous polyps and primary cancer there was no association between DCLK1 staining score and tumor pathology. However, after curative colorectal cancer resection, patients whose tumor had a high (≥5) combined staining score had increased cancer-specific mortality compared to patients with low (0-4) staining score (hazard ratio 5.89; 95% confidence interval: 1.22-28.47; P = 0.027). CONCLUSION: We found that DCLK1 is frequently expressed in colorectal neoplasia and may be associated with poor prognosis. Further studies are necessary to validate the use of DCLK1 as a prognostic marker.

Burkitt-like lymphoma arising in the thyroid gland.

INTRODUCTION: Primary Burkitt lymphoma of the thyroid gland is exceptionally rare. This highly aggressive, potentially curable malignancy arises from B cells. It presents as a rapidly expanding thyroid mass causing compressive symptoms. This article reports a very rare occurrence of Burkitt-like lymphoma in the thyroid, a variant of Burkitt lymphoma. METHODS: A 60-year-old white female developed a rapidly expanding thyroid mass associated with airway compression and difficulty in swallowing. RESULTS: Fine needle aspiration and cytometry studies established the diagnosis of lymphoma. The patient underwent an incisional neck biopsy which confirmed the final diagnosis according to the latest World Health Organization criteria. It was successfully treated with 1 cycle of appropriate therapeutic chemotherapy. CONCLUSION: In patients with lymphoma diagnosed on fine needle aspiration, an incisional thyroid and bone marrow biopsies are required to aid in the diagnosis and assure the appropriate chemotherapy protocol.

Cyclooxygenase-2 expression during immortalization and breast cancer progression.

Identification of molecular aberrations in premalignant human mammary epithelial cells (hMEC), the precursors for breast cancers, is a central goal in breast cancer biology. Recent studies implicated expression of cyclooxygenase 2 (COX-2) as a marker to identify precursor cells for breast cancer. In this study, we analyzed COX-2 expression in preselection and postselection hMEC cells and observed similar COX-2 levels in both cells. Interestingly, immortalization of postselection cells using various methods leads to a dramatic decrease in COX-2 expression. Similar to immortal cells, the majority of breast cancer cell lines expressed low levels of COX-2 protein. Finally, analyses of COX-2 expression in a series of specimens from reduction mammoplasty, adenosis, ductal carcinoma in situ, and infiltrating ductal carcinoma showed down-regulation of COX-2 expression during tumor progression. Importantly, down-regulation of COX-2 using small interfering RNA in cells showed no effect on cell proliferation, anchorage-independent growth, migration, or invasion. These results show that (a) COX-2 overexpression does not seem to predict a breast cancer precursor cell and does not provide advantage for the cell to be transformed; (b) inhibition of COX-2 does not affect hMEC growth and oncogenic behavior in the conditions analyzed; and (c) COX-2 expression is decreased in breast cancer cell lines and cancer specimens as compared with normal mammary epithelial cells.