An international Ki67 reproducibility study.

Background: In breast cancer, immunohistochemical assessment of proliferation using the marker Ki67 has potential use in both research and clinical management. However, lack of consistency across laboratories has limited Ki67's value. A working group was assembled to devise a strategy to harmonize Ki67 analysis and increase scoring concordance.

Calculator for ovarian carcinoma subtype prediction.

With the emerging evidence that the five major ovarian carcinoma subtypes (high-grade serous, clear cell, endometrioid, mucinous, and low-grade serous) are distinct disease entities, management of ovarian carcinoma will become subtype specific in the future. In an effort to improve diagnostic accuracy, we set out to determine if an immunohistochemical panel of molecular markers could reproduce consensus subtype assignment. Immunohistochemical expression of 22 biomarkers were examined on tissue microarrays constructed from 322 archival ovarian carcinoma samples from the British Columbia Cancer Agency archives, for the period between 1984 and 2000, and an independent set of 242 cases of ovarian carcinoma from the Gynaecologic Tissue Bank at Vancouver General Hospital from 2001 to 2008.

Primary ovarian mucinous carcinoma of intestinal type: significance of pattern of invasion and immunohistochemical expression profile in a series of 31 cases.

Primary ovarian mucinous carcinomas of the intestinal type are uncommon and earlier reports have included cases diagnosed according to older, less stringent, criteria (which would now be considered borderline tumors) and variable numbers of cases of metastatic adenocarcinoma. This study was conducted to identify all cases of primary mucinous carcinoma of the ovary in a population-based registry, diagnosed according to WHO 2003 criteria, and to characterize their histologic features, immunohistochemical expression profile, and outcome. Thirty-one cases of primary ovarian mucinous carcinoma were included in this study.

Mutation of FOXL2 in granulosa-cell tumors of the ovary.

Background: Granulosa-cell tumors (GCTs) are the most common type of malignant ovarian sex cord-stromal tumor (SCST). The pathogenesis of these tumors is unknown. Moreover, their histopathological diagnosis can be challenging, and there is no curative treatment beyond surgery.

Validation of immature adipogenic status and identification of prognostic biomarkers in myxoid liposarcoma using tissue microarrays.

Myxoid liposarcoma displays variably aggressive behavior and responds poorly to available systemic therapies. Expression profiling followed by tissue microarray validation linked to patient outcome is a powerful approach for validating biological mechanisms and identifying prognostic biomarkers. We applied these techniques to independent series of primary myxoid liposarcomas in an effort to assess markers of adipose differentiation in myxoid liposarcoma and to identify prognostic markers that can be efficiently assessed by immunohistochemistry.

Progesterone receptor is a significant factor associated with clinical outcomes and effect of adjuvant tamoxifen therapy in breast cancer patients.

Estrogen receptor status in breast cancer is associated with response to hormonal therapy and clinical outcome. The additional value of progesterone receptor (PR) has remained controversial. We examine the value of PR for prognosis and response to tamoxifen on a population-based series of 4,046 invasive early stage breast cancer patients.

IGF2BP3 (IMP3) expression is a marker of unfavorable prognosis in ovarian carcinoma of clear cell subtype.

Clear cell carcinoma is an uncommon subtype of ovarian carcinoma, accounting for 10% of cases. Clear cell carcinoma typically presents with stage I or II disease, and in this setting prognostic markers could aid in management decisions, in particular the decision to treat with adjuvant chemotherapy. We tested whether expression of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3, also known as IMP3) can serve as a new biomarker to predict outcome for patients with clear cell carcinoma and other subtypes of ovarian carcinoma.

Ovarian carcinoma subtypes are different diseases: implications for biomarker studies.

Background: Although it has long been appreciated that ovarian carcinoma subtypes (serous, clear cell, endometrioid, and mucinous) are associated with different natural histories, most ovarian carcinoma biomarker studies and current treatment protocols for women with this disease are not subtype specific. With the emergence of high-throughput molecular techniques, distinct pathogenetic pathways have been identified in these subtypes. We examined variation in biomarker expression rates between subtypes, and how this influences correlations between biomarker expression and stage at diagnosis or prognosis.

Kisspeptin and GPR54 immunoreactivity in a cohort of 518 patients defines favourable prognosis and clear cell subtype in ovarian carcinoma.

Background: Kisspeptins and their G-protein coupled receptor, GPR54 are required for GnRH release and have been associated with anti-metastatic tumour cell behaviour in model systems. The latter might suggest that their overexpression would be associated with a better prognosis in cancer. However, kisspeptin/GPR54 interactions (autocrine, paracrine, and/or endocrine) could also impact tumour behaviour in a negative manner.

Understanding the mechanism of the zinc-ion stains of biomacromolecules in electrophoresis gels: generalization of the reverse-staining technique.

We have recently shown that a few nanograms of protein separated by electrophoresis in sodium dodecyl sulfate-polyacrylamide gels can be detected by reverse-staining, exploiting the precipitation reaction between zinc(II) and imidazole. Modifications of this method have also been generated to detect gel-isolated nucleic acids and bacterial glycolipids. Because there is no recourse to chemical modifiers, the reverse-staining technique has been valuable when micropreparing these biomacromolecules for later use or characterization.

Risk factors for renal cell carcinoma in Denmark: role of medication and medical history.

Background: Several recent studies of risk factors for renal cell carcinoma have indicated that use of diuretics may increase risk of this cancer. It has also been suggested that use of weak analgesics, which are known to increase risk of cancer of the renal pelvis and ureter, may also be associated with an increased risk of renal cell carcinoma--the most frequent type of kidney cancer.

Methods: A population-based case-control study was undertaken to investigate the role of diuretics, other anti-hypertensive drugs, analgesics, and medical history in the aetiology of renal cell carcinoma.

The soluble human IL-6 receptor. Mutational characterization of the proteolytic cleavage site.

Like many proteins with a single transmembrane domain the IL-6R exists in a membrane-associated and soluble form. The soluble IL-6R is generated by limited proteolysis of the membranous receptor. This process, also called shedding, is drastically enhanced by PMA, an activator of protein kinase C.

A case-control and family study of Waldenstrom's macroglobulinemia.

Waldenstrom's macroglobulinemia (WM) is a rare disorder of lymphoid and plasma cells characterized by an immunoglobulin M (IgM) monoclonal gammopathy, clinical and immunopathologic similarities with other lymphoproliferative neoplasms, but the etiology of which is unknown. We undertook the first case-control study of this disorder among 65 cases, comprising 87% of all WM patients diagnosed during 1969-1983 in the greater Baltimore, Maryland area. Compared with 213 hospital controls without cancer, cases were slightly better educated, but there were otherwise no differences in sociodemographic factors, history of prior medical conditions, medication use, cigarette smoking, alcohol consumption, specific occupational exposures, employment in any particular industries or occupations, or familial cancer history.

GABA and glycine in synaptic vesicles: storage and transport characteristics.

gamma-Aminobutyric acid (GABA) and glycine are major inhibitory neurotransmitters that are released from nerve terminals by exocytosis via synaptic vesicles. Here we report that synaptic vesicles immunoisolated from rat cerebral cortex contain high amounts of GABA in addition to glutamate. Synaptic vesicles from the rat medulla oblongata also contain glycine and exhibit a higher GABA and a lower glutamate concentration than cortical vesicles.

A comparison of occupational data from death certificates and interviews.

A comparison was made of the occupational data reported on the death certificates of 586 men with their employment history obtained by interviews. Agreement was assessed for 19 occupational and 14 industrial categories of usual employment, with the highest levels of concordance (greater than or equal to 80%) found for agricultural, medical, and public administration activities. Between the two sources of information, there was overall agreement of 56% for usual occupation and 51% for usual industry of employment.

Comparison of next-of-kin with self-respondents regarding questions on cigarette, coffee, and alcohol consumption.

Using the same questionnaire, personnel, and field procedures, we conducted interviews in 1985 with the next-of-kin of 108 deceased study subjects, and with 197 surviving subjects who had been interviewed earlier in a 1980 case-control study. Concordance in response between the two interviews for cigarette smoking, coffee drinking, and alcoholic beverage intake was high, generally 90% or above. Next-of-kin, particularly spouses, provided information as reliable as the self-informants for cigarette smoking and coffee consumption, but showed a somewhat higher discrepancy rate for alcohol drinking.

Synaptic vesicles immunoisolated from rat cerebral cortex contain high levels of glutamate.

L-Glutamate is regarded as the major excitatory neurotransmitter in the mammalian CNS. However, whether the released transmitter originates from a cytosolic pool or is discharged from synaptic vesicles by exocytosis (vesicle hypothesis) remains controversial. A problem with the general acceptance of the vesicle hypothesis is that the enrichment of glutamate in synaptic vesicles has not been convincingly demonstrated.

A synaptic vesicle protein with a novel cytoplasmic domain and four transmembrane regions.

Complementary DNA and genomic clones were isolated and sequenced corresponding to rat and human synaptophysin (p38), a major integral membrane protein of synaptic vesicles. The deduced amino acid sequences indicate an evolutionarily highly conserved protein that spans the membrane four times. Both amino and carboxyl termini face the cytoplasm, with the latter containing ten copies of a tyrosine-rich pentapeptide repeat.

Relation of analgesic use to renal cancer: population-based findings.

A population-based case-control study of renal cancer (495 cases of renal cell cancer, 74 cases of renal pelvis cancer, and 697 controls) was conducted in the Minneapolis-St. Paul 7-county metropolitan area. Information was obtained on a large number of variables, including the use of analgesic drugs.

Petroleum-related employment and renal cell cancer.

The risk of renal cell cancer among those in occupations with potential for petroleum exposure was evaluated in a large population-based case-control study. Overall there was little difference between the cases and control groups in the proportion of persons with petroleum-related employment (odds ratio = 1.0).

Problems in the use of dead controls in case-control studies. II. Effect of excluding certain causes of death.

A recent comparison of 493 dead and 697 living controls from a case-control study of cancer in the Minneapolis-St. Paul area showed that the dead controls of both sexes were reported to have been significantly heavier consumers of cigarettes, hard liquor, beer, and certain drugs, and to have had more adulthood diseases than living controls. The present analysis examines the effect of excluding causes of death associated with those exposures found in excess in the dead controls.

Problems in the use of dead controls in case-control studies. I. General results.

A recently completed case-control study in the Minneapolis-St. Paul area using population-based living controls and dead controls afforded the opportunity to compare these two control groups on their exposure histories. Detailed information was obtained by interview from 697 living controls and the next of kin of 493 dead controls.

A population--based case--control study of renal cell carcinoma.

A population-based case-control study of renal cell carcinoma (495 cases and 697 controls) in the Minneapolis-St. Paul seven-county metropolitan area implicated cigarette smoking as a risk factor with an odds ratio (OR) among men of 1.6 (95% confidence intervals: 1.