Improving access to cervical cancer screening: The impact of a Saturday pap smear clinic.

Introduction: The implementation of cervical cancer screening and human papillomavirus (HPV) vaccination has significantly reduced cervical cancer rates. However, it remains the fourth most common cancer among women globally. Barriers to screening include personal, health system, and insurance factors.

Saturday Pap Smear Clinic: addressing barriers to cervical cancer screening.

Background: The incidence of cervical cancer has decreased by 70% since the 1950s. Preventative measures include vaccination against HPV strains and Papanicolaou tests. Early identification of cervical cancer through routine screening can significantly improve patient outcomes.

Papanicolaou test collection with the Papette brush or the spatula with cytobrush: A pragmatic study.

Background: Cotesting with the Papanicolaou (Pap) and human papillomavirus tests detects most precancerous and cancerous lesions and increases the sensitivity for detecting high-grade precancerous and invasive cervical cancers compared with human papillomavirus testing alone.

Objective: To compare the use of the Papette brush (hereafter Papette) to the traditional spatula with endocervical brush (cytobrush) for cervical cancer screening.

Design: Pragmatic observational study.

Postpartum depression in older women.

Postpartum depression, which affects 10% to 20% of women in the United States, can significantly harm the health and quality of life for mother, child, and family. This article reviews the risk factors, pathophysiology, clinical manifestations, diagnosis, and treatment of postpartum depression with specific focus on women of advanced maternal age.

Tumorgrafts as in vivo surrogates for women with ovarian cancer.

Purpose: Ovarian cancer has a high recurrence and mortality rate. A barrier to improved outcomes includes a lack of accurate models for preclinical testing of novel therapeutics.

Experimental Design: Clinically relevant, patient-derived tumorgraft models were generated from sequential patients and the first 168 engrafted models are described.

Discovery and validation of a prostate cancer genomic classifier that predicts early metastasis following radical prostatectomy.

Purpose: Clinicopathologic features and biochemical recurrence are sensitive, but not specific, predictors of metastatic disease and lethal prostate cancer. We hypothesize that a genomic expression signature detected in the primary tumor represents true biological potential of aggressive disease and provides improved prediction of early prostate cancer metastasis.

Methods: A nested case-control design was used to select 639 patients from the Mayo Clinic tumor registry who underwent radical prostatectomy between 1987 and 2001.

Inherited variant on chromosome 11q23 increases susceptibility to IDH-mutated but not IDH-normal gliomas regardless of grade or histology.

Introduction: Recent discoveries of inherited glioma risk loci and acquired IDH mutations are providing new insights into glioma etiology. IDH mutations are common in lower grade gliomas and secondary glioblastomas and uncommon in primary glioblastomas. Because the inherited variant in 11q23 has been associated with risk of lower grade glioma and not with glioblastomas, we hypothesized that this variant increases susceptibility to IDH-mutated gliomas, but not to IDH-wild-type gliomas.

A low-frequency variant at 8q24.21 is strongly associated with risk of oligodendroglial tumors and astrocytomas with IDH1 or IDH2 mutation.

Variants at 8q24.21 have been shown to be associated with glioma development. By means of tag SNP genotyping and imputation, pooled next-generation sequencing using long-range PCR and subsequent validation SNP genotyping, we identified seven low-frequency SNPs at 8q24.

p16-Cdk4-Rb axis controls sensitivity to a cyclin-dependent kinase inhibitor PD0332991 in glioblastoma xenograft cells.

Deregulation of the p16(INK4a)-Cdk4/6-Rb pathway is commonly detected in patients with glioblastoma multiforme (GBM) and is a rational therapeutic target. Here, we characterized the p16(INK4a)-Cdk4/6-Rb pathway in the Mayo panel of GBM xenografts, established from primary tissue samples from patients with GBM, and evaluated their response to PD0332991, a specific inhibitor of Cdk4/6. All GBM xenograft lines evaluated in this study had disruptions in the p16(INK4a)-Cdk4/6-Rb pathway.

MYC gene amplification is often acquired in lethal distant breast cancer metastases of unamplified primary tumors.

In breast cancer, amplification of MYC is consistently observed in aggressive forms of disease and correlates with poor prognosis and distant metastases. However, to date, a systematic analysis of MYC amplification in metastatic breast cancers has not been reported. Specifically, whether the MYC amplification status may change in metastases in comparison to the corresponding primary breast tumor, and potential variability among different metastases within the same patient have also not been assessed.

Primary central nervous system lymphomas: a validation study of array-based comparative genomic hybridization in formalin-fixed paraffin-embedded tumor specimens.

Purpose: Only a limited number of genetic studies have been conducted in primary central nervous system lymphomas (PCNSL), partly due to the rarity of the tumors and the very limited amount of available tissue. In this report, we present the first molecular characterization of copy number abnormalities (CNA) of newly diagnosed PCNSL by array-based comparative genomic hybridization (aCGH) in formalin-fixed paraffin-embedded (FFPE) specimens and compare the results with matched, frozen tumor specimens.

Experimental Design: We conducted aCGH in FFPE tissues from PCNSL.

Distinct germ line polymorphisms underlie glioma morphologic heterogeneity.

Two recent genome-wide association studies reported that single nucleotide polymorphisms (SNPs) in (or near) TERT (5p15), CCDC26 (8q24), CDKN2A/B (9p21), PHLDB1 (11q23), and RTEL1 (20q13) are associated with infiltrating glioma. From these reports, it was not clear whether the single nucleotide polymorphism associations predispose to glioma in general or whether they are specific to certain glioma grades or morphologic subtypes. To identify hypothesized associations between susceptibility loci and tumor subtype, we genotyped two case-control groups composed of the spectrum of infiltrating glioma subtypes and stratified the analyses by type.

Tubulin polymerization promoting protein (TPPP/p25) as a marker for oligodendroglial changes in multiple sclerosis.

Multiple sclerosis (MS) is an idiopathic chronic inflammatory demyelinating disease of the central nervous system with variable extent of remyelination. Remyelination originates from oligodendrocyte (OG) precursor cells, which migrate and differentiate into mature OG. Tubulin polymerization promoting protein (TPPP/p25) is located in mature OG and aggregates in oligodendroglial cytoplasmic inclusions in multiple system atrophy.

Fluorescence in situ hybridization to visualize genetic abnormalities in interphase cells of acinar cell carcinoma, ductal adenocarcinoma, and islet cell carcinoma of the pancreas.

Objective: To use fluorescence in situ hybridization (FISH) to visualize genetic abnormalities in interphase cell nuclei (interphase FISH) of acinar cell carcinoma, ductal adenocarcinoma, and islet cell carcinoma of the pancreas.

Patients And Methods: Between April 4, 2007, and December 4, 2008, interphase FISH was used to study paraffin-embedded preparations of tissue obtained from 18 patients listed in the Mayo Clinic Biospecimen Resource for Pancreas Research with a confirmed diagnosis of acinar cell carcinoma, ductal adenocarcinoma, islet cell carcinoma, or pancreas without evidence of neoplasia. FISH probes were used for chromosome loci of APC (see glossary at end of article for expansion of all gene symbols), BRCA2, CTNNB1, EGFR, ERBB2, CDKN2A, TP53, TYMP, and TYMS.

Validation of a new three-color fluorescence in situ hybridization (FISH) method to detect CHIC2 deletion, FIP1L1/PDGFRA fusion and PDGFRA translocations.

The PDGRFA locus has become a gene of interest based on mutational activation in various myeloid neoplasms and the availability of targeted therapies (i.e., imatinib mesylate) to its overexpression.

Incidence of TCR and TCL1 gene translocations and isochromosome 7q in peripheral T-cell lymphomas using fluorescence in situ hybridization.

Translocations involving the T-cell receptor (TCR) and TCL1 genes occur in T-cell precursor lymphoblastic leukemia/lymphoma and prolymphocytic leukemia; isochromosome 7q has been associated with hepatosplenic T-cell lymphoma. However, the incidence of these abnormalities in peripheral T-cell lymphomas (PTCLs) as a whole has not been well defined. We studied genetic abnormalities in 124 PTCLs seen at the Mayo Clinic, Rochester, MN, between 1987 and 2007.

Isochromosome (X)(p10) in hematologic disorders: FISH study of 14 new cases show three types of centromere signal patterns.

Though X chromosome anomalies are uncommon in hematologic malignancies, isodicentric X chromosomes, idic(X)(q13), with break and fusion points at Xq13 are well known among older females with de novo myelodysplasia. In contrast, only 17 patients with X isochromosomes involving break and fusion points at the centromere i(X)(p10) have been published, to our knowledge. We present 14 new patients with i(X)(p10) identified by G-banding and further characterized by fluorescence in situ hybridization (FISH) using probes for the X p-arm, X alpha-satellite DNA (DXZ1), and the XIST gene (Xq13).

Frequency, hematopathology, and detection of a new isodicentric variant of deletion 20q.

The ider(20)(p11.21)del(20)(q11q13) anomaly was recognized only recently. Thus, its frequency and clinical significance has not been extensively studied.

Efficacy of conventional cytogenetics and FISH for EGR1 to detect deletion 5q in hematological disorders and to assess response to treatment with Lenalidomide.

In clinical practice, whether FISH for EGR1 in interphase nuclei has similar efficacy to detect deletion 5q anomalies as conventional cytogenetic studies is unknown. We compared conventional cytogenetics and FISH for 145 patients with deletion 5q and detected this anomaly by both methods in 144. Nine patients with myelodysplasia were studied before and after treatment with Lenalidomide and results were concordant for 28 of 29 specimens.

The incidence and anatomic site specificity of chromosomal translocations in primary extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) in North America.

Several balanced translocations have been identified in extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) but there are few data regarding their frequency in different anatomic sites or the frequency of translocations involving BCL6 or kappa or lambda immunoglobulin light chain genes (IGK or IGL), particularly in patients from geographic regions other than Europe and Japan. One hundred thirty-three paraffin-embedded North American primary MALT lymphoma specimens from diverse anatomic sites were studied by fluorescence in situ hybridization (FISH) using probes for API2-MALT1, IGH-MALT1, IGH-BCL10, IGH-FOXP1, IGH, +/- centromeres 3, 7, 12, and 18, and a subset (n=74) were analyzed using FISH probes for IGK, IGL, and BCL6. Translocations were mutually exclusive and were detected in 26% of cases (17% API2-MALT1, 5% IGH-MALT1, 3% IGH-unknown translocation partner, and 1% IGH-BCL10).

Prospective evaluation of clonal evolution during long-term follow-up of patients with untreated early-stage chronic lymphocytic leukemia.

Purpose: Retrospective studies suggest cytogenetic abnormalities detected by interphase fluorescent in situ hybridization (FISH) can identify patients with chronic lymphocytic leukemia (CLL) who will experience a more aggressive disease course. Other studies suggest that patients may acquire chromosome abnormalities during the course of their disease. There are minimal prospective data on the clinical utility of the widely used hierarchical FISH prognostic categories in patients with newly diagnosed early-stage CLL or the frequency of clonal evolution as determined by interphase FISH.

Loss of TP53 is due to rearrangements involving chromosome region 17p10 approximately p12 in chronic lymphocytic leukemia.

Loss of tumor protein 53 (TP53) has been associated with aggressive disease and poor response to therapy in B-cell chronic lymphocytic leukemia (B-CLL). TP53 is located at chromosome band 17p13 and its absence can be detected by fluorescence in situ hybridization (FISH) in the interphase nuclei of 8-10% patients with B-CLL. To study the cytogenetic mechanism for loss of TP53, metaphase and interphase FISH studies were conducted on 16 B-CLL patients to investigate 17p10 to 17p12, a chromosome region known to be rich in low-copy DNA repeats.