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Christopher N Otis

Publications and source records attributed to Christopher N Otis.

18 recordsLinked to original sources
PubMed2006

Residency training in anatomic pathology: looking forward in the 21st century.

Residency training in anatomic pathology in the United States elicits a wide range of fundamental questions and conflicting opinions. This paper reflects the author's opinion concerning 4 questions that are often integral to these discussions and impact the outlook on training in the current century. (1) What are the goals of residency training in anatomic pathology? (2) In the face of exponential growth of information in anatomic pathology, how are residents to be trained? (3) What changes are likely to occur in the practice and training of anatomic pathology? (4) Is combined training in anatomic and clinical pathology a viable program for the 21st century?

Humans↗
PubMed2006

Use of an aggressive MCF-7 cell line variant, TMX2-28, to study cell invasion in breast cancer.

An estrogen receptor-negative variant of the MCF-7 breast cancer cell line, TMX2-28, was used as a model in which to study breast cancer cell invasion. Using a reconstituted basement membrane (Matrigel) assay to evaluate cell invasion, we determined that TMX2-28 cells are more invasive than MCF-7 cells and that the invasiveness of TMX2-28 is similar to that of the aggressive MDA-MB-231 breast cancer cell line. TMX2-28 cells displayed a rounded, epithelial cell-like morphology, suggesting an amoeboid mode of cell invasion, in contrast to the mesenchymal mode of invasion characteristic of spindle-shaped, fibroblast-like MDA-MB-231 cells. Using real-time reverse transcription-PCR, we found that mitogen-inducible gene 2 (MIG2) is expressed at a 17-fold higher level in TMX2-28 cells than in nonaggressive MCF-7 cells and that MIG2 mRNA levels are low in the nontumorigenic human mammary epithelial cell line, 184. We determined that MIG2 plays a role in cell invasion by using small interfering RNA (siRNA) to suppress the expression of MIG2 mRNA levels in TMX2-28 cells. TMX2-28 cell invasion was reduced by 48% when the cells were transfected with siRNAs targeting MIG2, relative to cells transfected with siRNAs against glyceraldehyde-3-phosphate dehydrogenase. Finally, MIG2 expression was evaluated in reductive mammoplasty and breast tumor tissue. Although all 21 normal tissues from reduction mammoplasty showed immunoreactivity for MIG2, ranging from weak (62%) to strong (24%), only half of the 34 formalin-fixed breast tumors showed immunoreactivity for MIG2. Of these 17 positive cases, 10 were considered to overexpress MIG2 (moderate to strong staining). Examination of 30 frozen breast tumors supported the finding that MIG2 is overexpressed in a subset of breast cancers. We suggest that MIG2's normal regulation and function are disrupted in breast cancer.

Breast Neoplasms↗
PubMed2006

The identification of ganglion cells in Hirschsprung disease by the immunohistochemical detection of ret oncoprotein.

The absence of ganglion cells (GCs) is the primary anatomic abnormality in Hirschsprung disease. Light microscopy is the mainstay in establishing this diagnosis. However, establishing a condition of aganglionosis may be challenging on routine H&E-stained sections of colonic biopsies and resections. We studied the identification of GCs by retinoblastoma oncoprotein (ret) immunoreactivity and routine H&E light microscopy by evaluating 53 blocks from 34 patients demonstrating GCs on original H&E-stained sections and 55 blocks from 38 patients lacking GCs on original H&E-stained sections. All blocks demonstrating GCs on H&E-stained sections also were positive for GCs on ret staining (100%). In 3 blocks that were negative for GCs by H&E staining (5%), GCs were shown on ret-stained sections. Immunoreactivity for ret has comparable specificity but slightly higher sensitivity to routine light microscopic evaluation in identifying GCs. GCs are identified more readily by ret immunoreactivity than by routine morphologic examination.

Biomarkers↗
PubMed2005

Diagnostic utility of p16 immunocytochemistry for Trichomonas in urine cytology.

We present a case in which p16 immunocytochemistry helped establish the diagnosis of Trichomonas in urine from a male patient. Based on this finding, we recommend p16 immunocytochemistry as a diagnostic tool for unexpected patients or specimen types in which potential trichomonads are identified following routine cytologic evaluation.

Journal Article↗
PubMed2005

Trichomonas vaginalis P16 Immunoreactivity in cervicovaginal Pap tests: a diagnostic pitfall.

Detection of p16 is emerging as a useful biomarker for Human Papillomavirus (HPV)-related dysplastic and malignant lesions of the cervix, and as such has potential application to cervicovaginal Papanicolaou (Pap) specimens. While evaluating p16 immunocytochemistry in our laboratory we observed one Pap test in which Trichomonas vaginalis stained positively for p16. We therefore proceeded to determine the frequency of T. vaginalis immunoreactivity for p16 in 10 consecutive, satisfactory, liquid-based Pap tests diagnosed as negative for intraepithelial lesion or malignancy in which T. vaginalis was present. For each case, a ThinPrep slide prepared from residual vial material was immunostained with p16. In an additional case, a prepared cell block was stained with p16. T. vaginalis were consistently p16 positive. We document, for the first time, p16 immunoreactivity of T. vaginalis that, on a Pap slide and cell block, may be morphologically misinterpreted as small dysplastic or malignant epithelial cells. The presence of this parasite in Pap tests may also potentially hinder the use of p16 as an adjunct to liquid-based cervical screening cytology.

Adolescent↗
PubMed2005

Fatal BK polyoma viral pneumonia associated with immunosuppression.

BK polyoma virus has a worldwide distribution in the human population. Primary BK infection takes place during childhood, with the virus remaining latent in many sites. Immunosuppressive states can lead to viral reactivation associated with many clinical sequelae. We report a case of fatal BK-related pneumonia in a 69-year-old patient who was immunocompromised because of chemotherapy for chronic lymphocytic leukemia. Immunohistochemical, in situ hybridization, and polymerase chain reaction studies on paraffin-embedded lung tissue proved BK virus as the etiologic agent of pneumonia. The histological picture was remarkable for numerous intranuclear large basophilic viral inclusions with ground-glass appearance mainly in type II pneumocytes. Similar to many other infectious agents, BK virus is emerging as an important pathogen in immunocompromised patients, making it important to consider in the differential diagnosis.

Aged↗
PubMed2005

Fallopian tube prolapse mimicking aggressive angiomyxoma.

A 68-year-old woman presented with a 4-cm polypoid bleeding mass protruding from the vaginal apex 30 years after vaginal hysterectomy. Laparotomy did not confirm the clinical suspicion of bowel prolapse and led to resection of the mass. Microscopic examination revealed a hypocellular edematous lesion with glandular areas resembling fallopian tube epithelium. Condensation of eosinophilic fibrils around medium sized vessels was marked. This case of fallopian tube prolapse shows an unusual resemblance of aggressive angiomyxoma and thus poses a diagnostic pitfall.

Aged↗
PubMed2004

Loss of heterozygosity occurs via mitotic recombination in Trp53+/- mice and associates with mammary tumor susceptibility of the BALB/c strain.

Loss of heterozygosity (LOH) occurs commonly in cancers causing disruption of tumor suppressor genes and promoting tumor progression. BALB/c-Trp53(+/-) mice are a model of Li-Fraumeni syndrome, exhibiting a high frequency of mammary tumors and other tumor types seen in patients. However, the frequency of mammary tumors and LOH differs among strains of Trp53(+/-) mice, with mammary tumors occurring only on a BALB/c genetic background and showing a high frequency of LOH, whereas Trp53(+/-) mice on a 129/Sv or (C57BL/6 x 129/Sv) mixed background have a very low frequency of mammary tumors and show LOH for Trp53 in only approximately 50% of tumors. We have performed studies on tumors from Trp53(+/-) mice of several genetic backgrounds to examine the mechanism of LOH in BALB/c-Trp53(+/-) mammary tumors. By Southern blotting, 96% (24 of 25) of BALB/c-Trp53(+/-) mammary tumors displayed LOH for Trp53. Karyotype analysis indicated that cells lacking one copy of chromosome 11 were present in all five mammary tumors analyzed but were not always the dominant population. Comparative genomic hybridization analysis of these five tumors indicated either loss or retention of the entire chromosome 11. Thus chromosome loss or deletions within chromosome 11 do not account for the LOH observed by Southern blotting. Simple sequence length polymorphism analysis of (C57BL/6 x BALB/c) F1-Trp53(+/-) mammary tumors showed that LOH occurred over multiple loci and that a combination of maternal and paternal alleles were retained, indicating that mitotic recombination is the most likely mechanism of LOH. Nonmammary tumors of BALB/c mice also showed a high frequency of LOH (22 of 26, 85%) indicating it was not a mammary tumor specific phenomenon but rather a feature of the BALB/c strain. In (C57BL/6 x BALB/c) F1-Trp53(+/-) mice LOH was observed in 93% (13 of 14) of tumors, indicating that the high frequency of LOH was a dominant genetic trait. Thus the high frequency of LOH for Trp53 in BALB/c-Trp53(+/-) mammary tumors occurs via mitotic recombination and is a dominant genetic trait that associates with the occurrence of mammary tumors in (C57BL/6 x BALB/c) F1-Trp53(+/-) mice. These results further implicate double-strand DNA break repair machinery as important contributors to mammary tumorigenesis.

Animals↗
PubMed2003

Fine-needle aspiration biopsy of the central nervous system performed freehand under computed tomography guidance without stereotactic instrumentation.

BACKGROUND: Biopsy of the central nervous system (CNS) has been reported previously using relatively large-caliber (12-17-gauge) biopsy instruments with or without stereotactic guidance. In this series, fine-needle aspiration biopsies (FNABs) were performed using a smaller diameter needle to evaluate mass lesions of the CNS. METHODS: One hundred thirty FNABs were performed freehand under computed tomography (CT) guidance without stereotactic instrumentation guidance using a 22-gauge needle. RESULTS: A definitive diagnosis was rendered in 97 of 130 FNABs (75%), including glioblastoma multiforme (GBM) (n = 33 biopsies); anaplastic astrocytoma (n = 14 biopsies); metastatic carcinoma (n = 13 biopsies); low-grade astrocytoma (LGA) (n = 10 biopsies); lymphoma (n = 7 biopsies); oligodendroglioma (n = 5 biopsies); reactive gliosis (n = 2 biopsies); and abscess (n = 13 biopsies), with the infectious agent identified in 7 of 13 biopsies. Immunohistochemistry was employed in 51 biopsies to assist in determining either the cell type or the infectious agent. Indefinite diagnoses were rendered in 33 patients (25%), including LGA versus gliosis (n = 8 patients), necrosis and/or inflammation (n = 3 patients), nondiagnostic material (n = 17 patients), suspicious for lymphoma (n = 2 patients), suspicious for GBM (n = 2 patients), and high-grade neoplasm not otherwise classified (n = 1 patient). There was no morbidity or mortality attributed to the procedure. CONCLUSIONS: FNAB of CNS mass lesions established a diagnosis based on cytologic interpretation in 75% of biopsies without morbidity or mortality. Because morbidity and mortality rates in CT-guided biopsies utilizing stereotactic techniques with large-caliber needles have been reported as high as 14% and 4.7%, respectively, freehand FNAB under CT guidance may be a preferred initial method for evaluating mass lesions of the CNS.

Adult↗
PubMed2003

BALB/c alleles for Prkdc and Cdkn2a interact to modify tumor susceptibility in Trp53+/- mice.

In mice heterozygous for p53 (Trp53(+/-)), the incidence of mammary tumors varies among strains, with C57BL/6 being resistant and BALB/c being susceptible. Mammary tumor phenotypes were examined in female Trp53(+/-) F1 mice (C57BL/6 x BALB/c;n = 19) and N2 backcross mice [(C57BL/6 x BALB/c) x BALB/c] (n = 224). Susceptibility to mammary tumors segregated as a dominant phenotype in F1 females, but a higher frequency and shorter latency in N2 mice indicated a contribution from recessive-acting modifiers. Segregation of the hypomorphic BALB/c alleles for DNA-dependent protein kinase catalytic subunit (Prkdc) and p16(INK4A) (Cdkn2a) was analyzed in the N2 mice. The time to first tumor (considering all tumor types) was significantly different among the four genotype combinations (P = 0.01). Cdkn2a had a strong effect (P = 0.008) but was restricted to Prkdc(B/B) mice (P = 0.001), indicating a strong interaction between the loci. Differences in mammary tumor occurrence among genotypes for Prkdc and Cdkn2a in N2 mice were not statistically significant. This study indicates that BALB/c Prkdc and Cdkn2a alleles do modify tumor incidence in Trp53(+/-) mice and highlights the complexity of gene interaction effects in determining cancer phenotypes but discounts these alleles as major recessive loci contributing to spontaneous mammary tumor susceptibility.

Alleles↗
PubMed2002

Atypical glandular cells of undetermined significance from extramammary Paget's of the bladder.

BACKGROUND: The clinical significance and appropriate diagnostic evaluation of atypical glandular cells of undetermined significance (AGCUS) on cervicovaginal Papanicolaou test have not been well established. CASE: A 53-year-old woman with AGCUS underwent colposcopy, cervical biopsy, hysteroscopy, dilation and fractional curettage, and subsequently hysterectomy with bilateral salpingo-oophorectomy without abnormal findings. A repeat vaginal Papanicolaou test revealed malignant cells. Extramammary Paget's disease and urothelial carcinoma in situ were subsequently determined to be the source of the abnormal cells interpreted as AGCUS. CONCLUSION: AGCUS may be associated with extramammary Paget's disease and urothelial carcinoma. One should maintain a high index of suspicion for extragenital causes of persistent AGCUS.

Carcinoma in Situ↗
PubMed2002

Loss of heterozygosity of p53, BRCA1, VHL, and estrogen receptor genes in breast carcinoma: correlation with related protein products and morphologic features.

Correlation of loss of heterozygosity (LOH) of p53, BRCA1, VHL, and estrogen receptor (ER) genes with the expression of related protein products and morphologic features predictive of aggressive biologic behavior was investigated to determine the significance of LOH in these genes. DNA from 35 formalin-fixed, paraffin-embedded breast carcinomas was obtained by microdissection of histologic sections. LOH was determined by polymerase chain reaction (PCR) using primers TP53, D3S1038, D17S855, and ESR for p53, VHL, BRCA1, and ER genes, respectively. p53, ER, and progesterone receptor (PR) protein expression was evaluated by immunohistochemistry. Morphologic evaluation included histologic type, and histologic and nuclear grades. TP53 LOH was identified in 13 (52%), BRCA1 LOH in 3 (17%), VHL LOH in 1 (4%), and ER LOH in 4 (21%) of 25, 17, 24, and 19 informative cases, respectively. p53 and ER protein expression was identified in 20 (57%) and 25 (71%) cases, respectively. TP53 LOH directly correlated with both high histologic and nuclear grade (P<0.01). BRCA1, VHL, and ER LOH was not frequent enough for correlation to morphologic features. Although 4 of 4 ER and 7 of 13 p53 LOH cases expressed related proteins, LOH did not correlate with protein expression. TP53 LOH may be an event contributing to aggressive biologic behavior since it is strongly associated with high histologic and nuclear grade. Missense or nonsense mutations may explain the absence of detectable p53 protein in 6 of 13 cases with p53 LOH. All 4 ER LOH cases expressed ER protein. BRCA1 and VHL LOH is infrequent in sporadic breast carcinoma.

Adenocarcinoma↗
PubMedDate not supplied

Beta-galactosidase and alpha-mannosidase inhibit formation of multicellular nodules in breast cancer cell cultures.

In response to an estrogen, confluent monolayers of MCF-7 cell cultures develop multi-cellular nodules, termed foci. Post-confluent development of foci occurs with physiologic levels of 17beta-estradiol and are inhibited by various anti-estrogens acting through either the estrogen or aryl hydrocarbon receptors. In the present paper we report that disruption of the terminal sugars on membrane receptors results in inhibition of foci. Treatment with 0.013-0.05 units/ml of beta-galactosidase completely inhibited the development of foci while leaving the monolayer of cells intact. Trials with alpha-mannosidase resulted in a similar but less potent inhibition of foci. Lectin-fluorescent conjugates, RCA (Ricinus communis agglutinin), and ConA (Canavalia ensiformis agglutinin) were used to identify membrane surface carbohydrates on MCF-7 cells. Binding of the RCA-fluorescent conjugate was inhibited by co-treatment with galactose or lactose. Binding of ConA-fluorescent conjugate was significantly inhibited by mannose and n-acetyl-glucosamine. This is the first report of inhibition of foci development in MCF-7 cell cultures by disruption of surface carbohydrates on membrane receptors.

Acetylglucosamine↗