Malignant mesothelioma in situ.

Aims: The existence of malignant mesothelioma in situ (MIS) is often postulated, but there are no accepted morphological criteria for making such a diagnosis.

Methods And Results: Here we report two cases that appear to be true MIS on the basis of in-situ genomic analysis. In one case the patient had repeated unexplained pleural unilateral effusions.

The miR-106a~363 miRNA cluster induces murine T cell lymphoma despite transcriptional activation of the p27 cell cycle inhibitor.

The miR-106a~363 cluster encodes 6 miRNAs on the X-chromosome which are abundant in blood cells and overexpressed in a variety of malignancies. The constituent miRNA of miR-106a~363 have functional activities that are predicted to be both oncogenic and tumor suppressive, yet little is known about their physiological functions . Mature miR-106a~363 () miRNAs are processed from an intragenic, non-protein encoding gene referred to as Xpcl1 (or ), situated at an X-chromosomal locus frequently targeted by retroviruses in murine lymphomas.

BAP1 Immunohistochemistry and p16 FISH in the Diagnosis of Sarcomatous and Desmoplastic Mesotheliomas.

The separation of sarcomatous and desmoplastic mesotheliomas from benign organizing pleuritis can be morphologically very difficult. Deletion of p16 (CDKN2A) by fluorescence in situ hybridization (FISH) testing appears to be a reliable marker of malignancy in mesothelial proliferations, and more recently it has been reported that, in this setting, loss of BAP1 by immunohistochemistry is only seen in malignant mesotheliomas. To determine how useful these tests are with sarcomatous and desmoplastic mesotheliomas, we examined 20 such tumors.

Evaluation of Human Epidermal Growth Factor Receptor 2 (HER2) Gene Status in Human Breast Cancer Formalin-Fixed Paraffin-Embedded (FFPE) Tissue Specimens by Fluorescence In Situ Hybridization (FISH).

Current standard of care requires that HER2 gene testing be performed on all newly diagnosed invasive breast cancers in order to determine eligibility for anti-HER2 antibody therapy and should be performed in accordance with current ASCO-CAP guidelines (Hammond et al., J Clin Oncol 29(15):e458, 2011; Wolff et al., J Clin Oncol 31(31):3997-4013, 2013).

Utility of BAP1 Immunohistochemistry and p16 (CDKN2A) FISH in the Diagnosis of Malignant Mesothelioma in Effusion Cytology Specimens.

The diagnosis of malignant mesothelioma in effusion cytology specimens is controversial. BAP1 immunohistochemistry and p16 fluorescence in situ hybridization (FISH) have recently been reported as reliable markers of malignancy in biopsies of mesothelioma. To determine whether these markers, singly or in combination, might also be useful in effusion cytology specimens, we examined 15 biopsies of epithelial mesotheliomas and 3 benign mesothelial reactions and corresponding effusion cytology paraffin-embedded cell blocks.

Personalized oncogenomics: clinical experience with malignant peritoneal mesothelioma using whole genome sequencing.

Peritoneal mesothelioma is a rare and sometimes lethal malignancy that presents a clinical challenge for both diagnosis and management. Recent studies have led to a better understanding of the molecular biology of peritoneal mesothelioma. Translation of the emerging data into better treatments and outcome is needed.

BAP1 immunohistochemistry and p16 FISH to separate benign from malignant mesothelial proliferations.

A variety of immunohistochemical (IHC) stains have been proposed to mark either benign or malignant mesothelial proliferations. Loss of the p16 tumor suppressor (CDKN2A), through homozygous deletions of 9p21, is a good marker of mesotheliomas but lacks sensitivity. Recent reports indicate that some mesotheliomas are associated with loss of BRCA-associated protein 1 (BAP1) expression.

Well-differentiated papillary mesothelioma with invasive foci.

Well-differentiated papillary mesotheliomas (WDPMs) are usually encountered as incidental findings in the peritoneal cavity in women. Most WDPMs are benign, and the histologic features that indicate a more aggressive course are controversial. We report 20 cases of WDPM, which contained invasive foci.

The effect of "single" vs "double" eyelids on the perceived attractiveness of Chinese women.

Background: A well-defined supratarsal crease has often been considered attractive, representing a significant component in a beautiful upper eyelid. Approximately 50% of East and Southeast Asian women are born with either a minimal or absent supratarsal eyelid crease. Among people of Chinese descent, the creation of a supratarsal crease ("double" eyelid blepharoplasty) is the most common cosmetic surgical procedure, but no comparative study has assessed the height by which an upper eyelid crease is deemed most attractive and depending on cultural background.

p16 FISH deletion in surface epithelial mesothelial proliferations is predictive of underlying invasive mesothelioma.

An atypical mesothelial proliferation along the pleural or peritoneal surface without evidence of invasive tumor poses a diagnostic challenge. Homozygous deletion of p16 (CDKN2A) by fluorescence in situ hybridization (FISH) has been shown to be a good marker of malignancy in mesothelial proliferations, but correlations of p16 status between atypical surface proliferations and underlying mesothelioma have not been described. We used p16 FISH to investigate 11 pleural and 7 peritoneal mesotheliomas that had both an invasive component and a separate surface mesothelial proliferation.

Determining true HER2 gene status in breast cancers with polysomy by using alternative chromosome 17 reference genes: implications for anti-HER2 targeted therapy.

Purpose: The ratio of human epidermal growth factor receptor 2 (HER2) to CEP17 by fluorescent in situ hybridization (FISH) with the centromeric probe CEP17 is used to determine HER2 gene status in breast cancer. Increases in CEP17 copy number have been interpreted as representing polysomy 17. However, pangenomic studies have demonstrated that polysomy 17 is rare.

Effect of Xpcl1 activation and p27(Kip1) loss on gene expression in murine lymphoma.

Mice lacking the p27(Kip1) Cdk inhibitor (Cdkn1b) exhibit increased susceptibility to lymphomas from the Maloney murine leukemia virus (M-MuLV), and exhibit a high frequency of viral integrations at Xpcl1 (Kis2), a locus on the X-chromosome. Xpcl1 encodes miR-106a~363, a cluster of microRNAs that are expressed in response to adjacent retroviral integrations. We report the first large-scale profile of microRNA expression in MuLV-induced lymphomas, in combination with microarray gene expression analysis.

Efficacy of preoperative neck ultrasound in the detection of cervical lymph node metastasis from thyroid cancer.

Objectives/hypothesis: This study was performed to assess the diagnostic accuracy of surgeon-performed preoperative neck ultrasound (US) in the detection of both central and lateral cervical lymph node metastases from thyroid cancer.

Study Design: Prospective cohort study.

Methods: Data for all patients with thyroid cancers and follicular thyroid lesions who were evaluated by means of preoperative neck US were reviewed.

Traumatic rhinoplasty in the non-Caucasian nose.

Traumatic injury resulting in nasal deformity poses unique challenges to the surgeon. Optimal management requires careful preoperative analysis and thoughtful surgical planning. The goals of rhinoplasty are to correct both cosmetic and functional problems that may not have otherwise been an issue prior to the injury.

Comparison of positron emission tomography/computed tomography imaging and ultrasound in staging and surveillance of head and neck and thyroid cancer.

Objectives/hypothesis: Positron emission tomography (PET) combined with cross-sectional computed tomography (CT) is increasingly used for staging and surveillance of cancers in the head and neck region. Ultrasonography (US) is an alternative imaging technique that provides diagnostic information while enabling simultaneous image-guided biopsies. A comparison of these diagnostic modalities in cancer detection is warranted.

Expansile bone cyst and cholesteatoma of the temporal bone.

Objective: To identify primary bony cysts of the temporal bone.

Patient: A single case of a woman presenting with unilateral bulging of the temporoparietal cranium, progressive stenosis of the external auditory canal, and maximal conductive hearing loss.

Intervention(s): Plain x-rays, magnetic resonance imaging, contrast-enhanced computed tomography, audiogram, and modified radical mastoidectomy.

Isoform- and cell cycle-dependent substrate degradation by the Fbw7 ubiquitin ligase.

The SCF(FBW7) ubiquitin ligase degrades proteins involved in cell division, growth, and differentiation and is commonly mutated in cancers. The Fbw7 locus encodes three protein isoforms that occupy distinct subcellular localizations, suggesting that each has unique functions. We used gene targeting to create isoform-specific Fbw7-null mutations in human cells and found that the nucleoplasmic Fbw7alpha isoform accounts for almost all Fbw7 activity toward cyclin E, c-Myc, and sterol regulatory element binding protein 1.

A mechanism misregulating p27 in tumors discovered in a functional genomic screen.

The cyclin-dependent kinase inhibitor p27(KIP1) is a tumor suppressor gene in mice, and loss of p27 protein is a negative prognostic indicator in human cancers. Unlike other tumor suppressors, the p27 gene is rarely mutated in tumors. Therefore misregulation of p27, rather than loss of the gene, is responsible for tumor-associated decreases in p27 protein levels.

Discovery of an oncogenic activity in p27Kip1 that causes stem cell expansion and a multiple tumor phenotype.

The cell cycle inhibitor p27Kip1 also has cyclin-cyclin-dependent kinase (CDK)-independent functions. To investigate the significance of these functions in vivo, we generated a knock-in mouse in which four amino acid substitutions in the cdkn1b gene product prevent its interaction with cyclins and CDKs (p27CK-). In striking contrast to complete deletion of the cdkn1b gene, which causes spontaneous tumorigenesis only in the pituitary, the p27CK- protein dominantly caused hyperplastic lesions and tumors in multiple organs, including the lung, retina, pituitary, ovary, adrenals, spleen, and lymphomas.

Analysis of gene expression, copy number and palindrome formation with a Dt40 enriched cDNA microarray.

DT40 presents a unique opportunity to exploit newly available tools for chicken genomic analysis. A 13K chicken cDNA microarray representing 11447 non-overlapping ESTs has been developed. This array detects expression of 7086 DT40 genes of which_644 are over-expressed 3-fold or greater and 1585 are under-expressed 3-fold or greater relative to normal post-hatch bursal cell populations.

Intracystic papillary carcinomas of the breast: a reevaluation using a panel of myoepithelial cell markers.

Intracystic papillary carcinomas (IPC) of the breast have traditionally been considered to be variants of ductal carcinoma in situ (DCIS). However, it is not clear if all lesions categorized histologically as IPC are truly in situ carcinomas, or if some such lesions might represent circumscribed or encapsulated nodules of invasive papillary carcinoma. Given that the demonstration of a myoepithelial cell (MEC) layer around nests of carcinoma cells is a useful means to distinguish in situ from invasive carcinomas of the breast in problematic cases, assessment of the presence or absence of a MEC layer at the periphery of the nodules that comprise these lesions could help resolve this issue.

Evaluation of 12 antibodies for distinguishing epithelioid mesothelioma from adenocarcinoma: identification of a three-antibody immunohistochemical panel with maximal sensitivity and specificity.

We evaluated the sensitivity and specificity of 10 monoclonal and two polyclonal antibodies for distinguishing epithelioid mesothelioma from adenocarcinoma (AdCA) using immunohistochemistry (IHC). The antibodies were directed against the mesothelial-associated antigens mesothelin, calretinin, cytokeratin 5, thrombomodulin, Wilms' tumor-1 (WT-1) gene product and HBME-1, and the nonmesothelial antigens Lewis-Y blood group (antibody BG8), MOC-31, BerEp4, CD15, and carcinoembryonic antigen (CEA) family. The 133 tumors evaluated included 65 malignant epithelioid mesotheliomas, 22 lung AdCAs, 27 ovarian serous carcinomas, 24 breast carcinomas, and five gastric carcinomas.

Zcchc8 is a glycogen synthase kinase-3 substrate that interacts with RNA-binding proteins.

Phosphorylation of c-Myc on threonine 58 (T58) stimulates its degradation by the Fbw7-SCF ubiquitin ligase. We used a phosphorylation-specific antibody raised against the c-Myc T58 region to attempt to identify other proteins regulated by the Fbw7 pathway. We identified two predominant proteins recognized by this antibody.

Cyclin E in normal and neoplastic cell cycles.

Cyclin E-Cdk2 has long been considered an essential and master regulator of progression through G1 phase of the cell cycle. Although recent mouse models have prompted a rethinking of cyclin E function in mammals, it remains clear that cyclin E impacts upon many processes central to cell division. Normal cells maintain strict control of cyclin E activity, and this is commonly disrupted in cancer cells.