Longitudinal outcome study of sessile serrated adenomas of the colorectum: an increased risk for subsequent right-sided colorectal carcinoma.

Sessile serrated adenomas (SSAs) are associated with colorectal carcinomas (CRCs) that demonstrate high microsatellite instability (MSI-H). Currently, SSAs are managed clinically in a similar fashion to adenomatous polyps (APs). We studied the natural history of SSA by analyzing the outcome of previously undiagnosed SSAs and comparing it with that of hyperplastic polyps (HPs) and APs.

Type I gamma phosphatidylinositol phosphate kinase modulates invasion and proliferation and its expression correlates with poor prognosis in breast cancer.

Introduction: The loss of E-cadherin based cell-cell contacts and tumor cell migration to the vasculature and lymphatic system are hallmarks of metastasis of epithelial cancers. Type I gamma phosphatidylinositol phosphate kinase (PIPKIgamma), an enzyme that generates phosphatidylinositol 4,5-bisphosphate (PI4,5P2) a lipid messenger and precursor to many additional second messengers, was found to regulate E-cadherin cell-cell contacts and growth factor-stimulated directional cell migration, indicating that PIPKIgamma regulates key steps in metastasis. Here, we assess the expression of PIPKIgamma in breast cancers and have shown that expression correlated with disease progression and outcome.

A panel of antibodies to determine site of origin and malignancy in smooth muscle tumors.

Leiomyosarcomas are malignant smooth muscle tumors that occur most commonly in the gynecologic tract and soft tissue. There are different diagnostic criteria of malignancy for smooth muscle tumors arising at gynecologic and soft tissue sites and they may be managed differently but determining the primary site of a smooth muscle tumor can be difficult in some cases. In addition, the distinction between malignant and benign gynecologic tract smooth muscle tumors on morphologic grounds can be challenging.

Automated quantitative analysis of estrogen receptor expression in breast carcinoma does not differ from expert pathologist scoring: a tissue microarray study of 3,484 cases.

Background: Estrogen receptor (ER) expression is routinely assessed by immunohistochemistry (IHC) in breast carcinoma. Our study compares visual scoring of ER in invasive breast cancer by histopathologists to quantitation of staining using a fully automated system.

Materials And Methods: A tissue microarray was constructed from 4,049 cases (3,484 included in analysis) of invasive breast carcinoma linked to treatment and outcome information.

Raft-dependent endocytosis of autocrine motility factor is phosphatidylinositol 3-kinase-dependent in breast carcinoma cells.

Autocrine motility factor (AMF) is internalized via a receptor-mediated, dynamin-dependent, cholesterol-sensitive raft pathway to the smooth endoplasmic reticulum that is negatively regulated by caveolin-1. Expression of AMF and its receptor (AMFR) is associated with tumor progression and malignancy; however, the extent to which the raft-dependent uptake of AMF is tumor cell-specific has yet to be addressed. By Western blot and cell surface fluorescence-activated cell sorter (FACS) analysis, AMFR expression is increased in tumorigenic MCF7 and metastatic MDA-231 and MDA-435 breast cancer cell lines relative to dysplastic MCF10A mammary epithelial cells.

Stromal mast cells in invasive breast cancer are a marker of favourable prognosis: a study of 4,444 cases.

Purpose: We have previously demonstrated in a pilot study of 348 invasive breast cancers that mast cell (MC) infiltrates within primary breast cancers are associated with a good prognosis. Our aim was to verify this finding in a larger cohort of invasive breast cancer patients and examine the relationship between the presence of MCs and other clinical and pathological features.

Experimental Design: Clinically annotated tissue microarrays (TMAs) containing 4,444 cases were constructed and stained with c-Kit (CD-117) using standard immunoperoxidase techniques to identify and quantify MCs.

Type I gamma phosphatidylinositol phosphate kinase modulates adherens junction and E-cadherin trafficking via a direct interaction with mu 1B adaptin.

Assembly of E-cadherin-based adherens junctions (AJ) is obligatory for establishment of polarized epithelia and plays a key role in repressing the invasiveness of many carcinomas. Here we show that type Igamma phosphatidylinositol phosphate kinase (PIPKIgamma) directly binds to E-cadherin and modulates E-cadherin trafficking. PIPKIgamma also interacts with the mu subunits of clathrin adaptor protein (AP) complexes and acts as a signalling scaffold that links AP complexes to E-cadherin.

Expression of protein elongation factor eEF1A2 predicts favorable outcome in breast cancer.

Breast cancer is the most common malignancy among North American women. The identification of factors that predict outcome is key to individualized disease management and to our understanding of breast oncogenesis. We have analyzed mRNA expression of protein elongation factor eEF1A2 in two independent breast tumor populations of size n = 345 and n = 88, respectively.

MDM2 protein expression is a negative prognostic marker in breast carcinoma.

The protein encoded by the MDM2 oncogene inhibits the function of p53, leading to increased cell growth, avoidance of apoptosis, tolerance of genetic instability, and resistance to chemotherapy. The present study was performed to evaluate the relationship between MDM2 protein expression and survival in breast carcinoma. Two series of cases were used in this study: the first to identify the cutoff to be used in the interpretation of MDM2 immunostaining and perform preliminary survival analysis, and a second, independent series, to validate the findings from the first series and to perform multivariate analysis.

TMA-Combiner, a simple software tool to permit analysis of replicate cores on tissue microarrays.

We have previously published a suite of software tools that facilitates the reformulation of tissue microarray (TMA) data so that it may be analyzed using techniques originally devised for analysis of cDNA microarray data. However, current microarray data often feature multiple scores for a given tissue sample and antibody combination. Furthermore, an efficient and systematic method for combining scores that takes into account the differing staining properties of tissue epitopes has not been described.

Nuclear beta-catenin in mesenchymal tumors.

Beta-catenin is a crucial part of the Wnt and E-cadherin signalling pathways, which are involved in tumorigenesis. Dysregulation of these pathways allow beta-catenin to accumulate and translocate to the nucleus, where it may activate oncogenes. Such nuclear accumulation can be detected by immunohistochemistry, which may be useful in diagnosis.