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T Gorey

Publications and source records attributed to T Gorey.

13 recordsLinked to original sources
PubMed1999

Frequent loss of imprinting of PEG1/MEST in invasive breast cancer.

The human PEG1 gene is a newly identified imprinted gene on 7q32. Genetic aberrations of this chromosomal region are often detected in invasive breast carcinomas. In this study, we show monoallelic PEG1 expression in normal breast tissue, indicating the presence of a functional imprint, and more importantly, we demonstrate loss of imprinting (LOI) in all of seven informative invasive breast carcinomas. In contrast to this, in one case of atypical ductal hyperplasia (ADH) found in residual breast, imprinting was maintained. This raises the possibility that aberrant imprinting of PEG1 may be involved in the progression from hyperplasia to invasive breast cancer.

Alleles↗
PubMed1999

Widespread chromosomal abnormalities in high-grade ductal carcinoma in situ of the breast. Comparative genomic hybridization study of pure high-grade DCIS.

For a variety of technical reasons it is rarely possible to study cytogenetic abnormalities in ductal carcinoma in situ (DCIS) using traditional techniques. However, by combining molecular biology and computerized image analysis it is possible to carry out cytogenetic analyses on formalin-fixed, paraffin-embedded tissue, using comparative genomic hybridization (CGH). The purpose of this study was to identify the prevalence of chromosomal amplifications and deletions in high-grade DCIS and to look specifically for unique or consistent abnormalities in this pre-invasive cancer. Twenty-three cases of asymptomatic, non-palpable, screen-detected, high-grade DCIS were examined using CGH on tumour cells obtained from histology slides. All cases showed chromosomal abnormalities. A wide variety of amplifications and deletions were spread across the genome. The most frequent changes were gains of chromosomes 17 (13 of 23), 16p (13 of 23), and 20q (9 of 23) and amplifications of 11q13 (22 of 23), 12q 24.1-24.2 (12 of 23), 6p21.3 (11 of 23), and 1q31-qter (6 of 23). The most frequent deletions were on 13q 21.3-q33 (7 of 23), 9p21 (4 of 23), and 6q16.1 (4 of 23). These findings indicate that high-grade DCIS is, from a cytogenetic viewpoint, an advanced lesion. There was no absolutely consistent finding in every case, but amplification of 11q13 was found in 22 of the 23 cases. The precise significance of this is unknown at present. This region of chromosome 11q harbours a number of known oncogenes, including cyclin D1 andINT2. It is likely that many of these findings are the result of accumulated chromosomal abnormalities, reflecting an unstable genome in established malignancy.

Breast Neoplasms↗
PubMed1999

Loss of heterozygosity of the Wilms' tumor suppressor gene (WT1) in in situ and invasive breast carcinoma.

The Wilms' tumor suppressor gene (WT1), a nuclear transcription factor, regulates the expression of the insulin-like growth factor (IGF) and transforming growth factor (TGF) systems, both of which are implicated in breast tumorigenesis. WT1 allelic integrity was examined by loss of heterozygosity (LOH) studies in formalin-fixed, paraffin-embedded (FFPE) ductal carcinoma in situ (DCIS, n = 20) and fresh frozen primary invasive breast carcinomas (n = 24). Loss of heterozygosity (LOH) at the WT1 locus (11p13) was examined by PCR evaluation of an Hinf1 restriction fragment length polymorphism (RFLP) and correlated to tumor stage (in situ and invasive). After identification of the heterozygous/informative breast lesions, 1 of 12 (8.3%) DCIS (high-grade micropapillary) and 3 of 14 (21.4%) of infiltrating carcinomas (high grade) showed loss of one allele, suggesting that LOH of the WT1 locus is a rare genetic event in early breast cancer, becoming more common in invasive and in high-grade lesions.

Breast Neoplasms↗
PubMed1998

Tc-99m tetrofosmin scintigraphy as an adjunct to plain-film mammography in palpable breast lesions.

AIM: To investigate the use of Tc-99m tetrofosmin as a breast imaging agent and to compare results of Tc-99m tetrofosmin scintimammography with plain-film mammography and pathological outcome. PATIENTS AND METHODS: Forty-four patients (mean age, 51 years; range 26-79 years) with a palpable breast mass requiring fine needle aspiration biopsy (FNAB) were prospectively studied. All patients had Tc-99m tetrofosmin scintimammography. Patients over 35 years of age had two view mammography performed on the same day. FNAB was performed within 2 weeks of imaging, and patients referred for surgery as appropriate. Results of scintigraphy and plain-film mammography were correlated with pathological outcome. RESULTS: Of the 44 patients, 21 had biopsy proven malignancy while 23 had benign lesions. Of the 21 patients with carcinoma, 20 (95.2%) had positive Tc-99m tetrofosmin scintimammography while 21 (91.3%) of the 23 patients with benign histology had negative scintigraphy. The sensitivity of scintimammography was 95.24%, the specificity was 91.3%, with a positive predictive value of 90.9% and a negative predictive value of 95.45%. Thirty-eight patients had two view mammography performed (six patients were <35 years of age). Of these 38 patients, 21 had biopsy proven malignancy while 17 had benign histology (all patients <35 years of age had benign histology). Of the 21 patients with malignancy, plain-film mammography was suspicious for malignancy in 17 (81%) while four were reported as benign. Of the 17 with benign disease, 14 patients (82.4%) had benign appearances on plain-film mammography while three (18%) had one or more findings suspicious for malignancy. The sensitivity of plain-film mammography in our group was 81%, with a specificity of 82.4%, a positive predictive value of 85% and a negative predictive value of 77.8%. Tc-99m tetrofosmin scintimammography correctly characterized all seven lesions where mammographic evaluation was limited because of dense breast parenchyma or previous surgery and/or radiotherapy. CONCLUSION: Tc-99m tetrofosmin scintimammography is an accurate, well tolerated and non-invasive method of differentiating benign from malignant palpable breast lesions. Negative Tc-99m tetrofosmin scintimammography excludes malignancy with a high degree of confidence while false-positive scintigraphy can occur in cases of proliferative dysplasia and hypercellular fibroadenoma. Tc-99m tetrofosmin scintimammography is particularly useful when plain-film mammography is indeterminate or limited in patients with dense breasts or a history of previous surgery and/or radiotherapy.

Adult↗
PubMed1997

The MAS proto-oncogene is imprinted in human breast tissue.

The human MAS proto-oncogene is situated at 6q25.3-q26, a region that is homologous to mouse chromosome 17 where two parentally imprinted genes (Mas and Igf2r) have previously been identified. We investigated the imprinting status of MAS in adult lesions to establish the imprinting status of this gene in humans, as certain imprinted genes are known to have altered imprinting phenotypes in cancer. Of 14 breast samples demonstrating a MAS RT-PCR product, 4 were informative for a polymorphic marker. In all 4 cases, expression of the MAS gene was found to be mono-allelic, indicating the presence of a functional imprint at this locus in human breast tissue.

Adult↗
PubMed1997

Benign versus malignant breast disease: comparison of contrast-enhanced MR imaging and Tc-99m tetrofosmin scintimammography.

PURPOSE: To compare technetium-99m tetrofosmin scintimammography with contrast material-enhanced magnetic resonance (MR) imaging in the characterization of palpable breast masses. MATERIALS AND METHODS: Forty-seven patients (mean age, 51 years) with a palpable breast mass were prospectively examined with scintimammography, MR imaging, and conventional mammography 2 weeks before fine-needle aspiration biopsy. RESULTS: In three patients, MR imaging was aborted. Of the remaining 44 patients, 21 had biopsy-proved cancer and 23 had benign disease. The sensitivity of mammography was 81%; specificity, 82%; positive predictive value (PPV), 85%; and negative predictive value (NPV), 78%. The sensitivity of scintimammography was 95%; specificity, 91%; PPV, 91%; and NPV, 95%. The sensitivity of MR imaging was 90%; specificity, 91%; PPV, 90%; and NPV, 91%. In 11 patients with previous breast cancer, scintimammographic findings were positive in all four with tumor recurrence and negative in all seven with benign disease. Masses were correctly characterized with MR imaging in eight of these 11 patients. CONCLUSION: Although both techniques accurately differentiate benign from malignant palpable breast masses, scintimammography is more accurate in the posttreatment breast. Because of lower cost, wider availability, and high patient acceptance, scintimammography may provide a valuable alternative to MR imaging for noninvasive characterization of palpable breast disease.

Adult↗
PubMed1996

Comparison of oestrogen receptor assessment in frozen and paraffin sections.

Estimation of oestrogen receptors (ER) in breast carcinoma has important therapeutic and prognostic implications. The dextran-coated charcoal (DCC) biochemical technique is being replaced in many institutions by immunohistochemical techniques. The aim of this study was to assess the level of agreement between ER counts in frozen and paraffin sections. Ninety-seven infiltrating breast carcinomas were studied immunohistochemically, for ER in frozen and paraffin sections. Cases were classified as ER-positive if > or = 10% of the tumor cells were positive. Both techniques gave a high level of correlation and agreement. There was complete agreement in classifying cases as ER-positive or ER-negative. ER estimation on only one case was outside 2SD of complete agreement. Oestrogen-receptor content can be assayed satisfactorily in paraffin sections and offers many advantages over the frozen section technique.

Frozen Sections↗
PubMed1996

Comparison of cytomorphological and architectural heterogeneity in mammographically-detected ductal carcinoma in situ.

Many classification schemes have been proposed for ductal carcinoma in situ. Architectural heterogeneity is widely recognized. Cytonuclear grade appears to have greater prognostic significance than architectural pattern. This study assesses heterogeneity using a classification based on cytological grade and compares this to architectural heterogeneity in mammographically detected ductal carcinoma in situ. One hundred and twelve cases were classified according to architectural subtypes and the carcinoma nuclei were graded. Necrosis and microcalcification were assessed. Eighty-four percent of ductal carcinomas in situ had a single nuclear grade, whereas only 39% showed a single architectural pattern. High grade nuclei were present in 87% of cases. Necrosis was associated with high nuclear grade. In contrast to architectural heterogeneity, this study shows little ductal carcinoma in situ heterogeneity when classification is based on nuclear grade. Thus, a cytomorphological classification should have the advantage of consistency and reproducibility in comparison to architecture-based classification systems.

Aged↗
PubMed1996

Biallelic expression of the IGF2 gene in human breast disease.

We examined the imprinting status of the insulin-like growth factor II gene (IGF2) in a series of 20 human breast disease samples to determine if disrupted imprinting (as evidenced by biallelic expression), was a demonstrable mechanism of altered gene expression. These samples included benign (n = 7) and malignant breast lesions (n = 13). Biallelic expression of IGF2 was detectable in 67% of benign and 60% of malignant informative breast lesions. Three informative reduction mastectomies displayed normal IGF2 imprinting. The presence of this alteration in human breast tissue is a novel finding, and may contribute to tumorigenesis, possibly by favouring an enhanced proliferative milieu, during which additional mutations could occur.

Adult↗
PubMed1994

Heading in a new direction.

Health system reform may be down the road, but significant changes in the environment in which Iowa physicians practice are just around the corner. In the near future, the growth of managed care will have a profound effect on health care delivery. What are your options in this new environment?

Health Care Reform↗
PubMed1984

Doppler localisation of intrarenal vessels: an experimental study.

The use of the Doppler probe to localise the intrarenal vessels was assessed in 15 dogs. This prevented the need for renal artery clamping and radial nephrotomies were placed in silent areas on the renal surface. Functional studies were performed post-operatively at 48 h and 1 month, using creatinine clearance, microfil casts and cast angiography. There was no significant loss of function when three or six radial nephrotomies were made and the Doppler accurately localised sites for nephrotomy between the intrarenal arteries and veins which were undamaged.

Angiography↗
PubMedDate not supplied

Enhanced in vitro growth suppression of human glioblastoma cultures treated with the combination of recombinant fibroblast and immune interferons.

In the present study we have evaluated the effect of recombinant human fibroblast, IFN-beta ser, and immune, IFN-gamma, interferon, alone and in combination, on the proliferation of fifteen early passage human glioblastoma cell cultures. Explant cultures were established from glioblastoma tumor tissue obtained at the time of surgery. After sufficient outgrowth, cultures were dispersed with trypsin/versene and maintained as independent cell lines. IFN-beta ser induced a greater than or equal to 50% reduction in the 7 day growth of 6 of the 15 cultures. The majority of cultures, 9 of 15, displayed less than or equal to 50% growth suppression in comparison with control cultures after 7 days exposure to 2000 Units/ml of IFN-beta ser. When treated with 2000 Units/ml of IFN-gamma, only 1 of the 15 glioblastoma cultures exhibited a greater than or equal to 50% reduction in growth. In contrast, when treated with the combination of IFN-beta ser plus IFN-gamma, 1000 Units/ml of each interferon preparation, 12 of 15 cultures were inhibited by greater than or equal to 50% after 7 days growth. The combination of interferons was effective in suppressing glioblastoma growth both in cultures displaying relative sensitivity and those exhibiting innate resistance to either or both types of interferon when employed alone. One glioblastoma culture, G-7, was studied through 45 passages and displayed the same sensitivity at different passages to growth inhibition when exposed to IFN-beta ser, IFN-gamma or both interferons. Based on previous clinical studies indicating that IFN-beta or IFN-gamma when administered alone to patients do not generally alter the clinical progression of malignant gliomas, the present results suggest that the combination of IFN-beta plus IFN-gamma may prove more effective than either agent alone in the clinical treatment of patients with glioblastoma multiforme.

Brain Neoplasms↗