Biomedical subjects

Raymond R Tubbs

Publications and source records attributed to Raymond R Tubbs.

42 records · Page 3Linked to original sources

PubMed2002

Diffuse large B-cell lymphoma of the stomach: assessment of microsatellite instability, allelic imbalance, and trisomy of chromosomes 3, 12, and 18.

Several types of genetic aberrations including microsatellite instability (MSI), allelic imbalance (AI), and chromosomal trisomies have been reported in low-grade (LG) mucosa-associated lymphoid tissue (MALT)-type gastric lymphomas. Presence of such genetic alterations could be a discriminator between de novo large cell lymphoma and high-grade (HG) MALT-type lymphoma. We investigated 17 primary gastric large B-cell lymphomas with and without features of MALT-type lymphoma for MSI, AI, and presence of trisomy of chromosomes 3, 12, and 18. We studied resection specimens from 17 primary gastric extranodal diffuse large B-cell lymphomas. Cases classified as HG MALT-type lymphoma, based on either the presence of LG MALT-type lymphoma component in the background (L/H MALT) or large cell lymphoepithelial lesions (HG MALT), and diffuse large B-cell lymphoma (DLBCL-NOS) when no features of MALT were present. MSI was analyzed using fluorescently labeled polymerase chain reaction primers (D3S11, D6S262, D3S1261, D3S1262, D3S1265). Paired tumor and normal DNA samples were amplified, and PCR products were analyzed on a DNA sequencer (ABI PRISM 373XL) with GeneScan (Applied Biosystems, Foster City, CA). MSI was defined as a gain of a novel-length allele compared with the corresponding normal tissue. AI was assessed at locus 3q27 (D3S1262 and D3S1265). The cases were analyzed for the presence of trisomy of chromosomes 3, 12, and 18 using interphase fluorescence in situ hybridization. MSI was detected in 4 out of 15 (27%) cases from which DNA was amplifiable with all primers and all MALT-type lymphomas. In two cases (13%), MSI was present at two loci sufficient to be classified as high-frequency MSI (MSI-H); this was seen exclusively in HG MALT lymphomas (P = 0.04). In the remaining two cases, MSI was detected at a single locus (low-frequency MSI). Allelic imbalance at the locus D3S1262 was detected in 4 out of 17 (24%) cases. It occurred more commonly in stage IE lymphomas when compared with higher stages (P = 0.03), regardless of lymphoma subtype. Trisomy 12 was detected in 3 out of 17 cases (18%) exclusively in stage IE lymphomas (P = 0.08). MSI was uncommon and was found exclusively in MALT-type lymphomas. MSI-H was even less common but occurred in HG MALT lymphomas only. Allelic imbalance at 3q27 (D3S1262) and trisomy 12 were found more commonly in low-stage disease. The latter two findings are in concordance with the recent suggestion that the published variation in gain of chromosomal material in high-grade gastric lymphomas may be related to stage rather than to the subtype of lymphoma. Because of the relatively low frequency of MSI in the high-grade B-cell lymphomas of the stomach, this feature cannot be used to reliably discriminate between the histologic types of extranodal diffuse large B-cell lymphoma.

Allelic Imbalance↗

PubMed2002

Tissue microarrays: a powerful tool for high-throughput analysis of clinical specimens: a review of the method with validation data.

With recent advances in the knowledge of human molecular genetics, new gene-based disease mechanisms are emerging in many areas of medicine. The study of new prognostic and diagnostic markers in large numbers of clinical specimens is an important step in translating the new findings from basic science to clinical practice. The recently developed tissue microarray technology allows parallel molecular profiling of clinical samples at the DNA, RNA, and protein level. This technique enables pathologists to perform large-scale analyses using immunohistochemistry, fluorescence in situ hybridization, or RNA in situ hybridization substantially faster and at markedly lower costs compared with the conventional approach. This article provides a short review of this technology, focuses on several technical aspects of tissue microarray construction, and addresses the validity of the tissue microarray results for clinical research by reviewing data from recent literature along with the authors' own data.

Humans↗

PubMed2002

Demonstration of immune complex deposits using fluorescence microscopy of hematoxylin and eosin-stained sections of Hollande's fixed renal biopsies.

A new method that may be useful in the evaluation of renal biopsies is described using fluorescence microscopy on standard hematoxylin and eosin-stained sections of kidney tissue fixed in Hollande's fixative. We describe brightly fluorescing immune complex deposits within glomerular basement membranes and mesangial matrices that correlate well with the results of standard direct immunofluorescence on frozen tissue and electron microscopy. In a blind analysis of 261 consecutive renal biopsies, we determine that this method has diagnostic utility for identification of immune complex glomerulonephritis and significantly extends the usefulness of standard histologic preparations before the use of special stains or procedures.

Antigen-Antibody Complex↗

PubMed2002

HER2/neu amplification in breast cancer: stratification by tumor type and grade.

The presence of HER2/neu gene amplification is prognostically and therapeutically significant for patients with breast cancer. We sought to determine whether a relationship exists between HER2/neu gene amplification and the histologic type and grade of tumor. The histologic features and corresponding HER2/neu amplification results of 401 cases of invasive breast carcinoma were reviewed. Lobular carcinomas were less likely than ductal carcinomas to have HER2/neu amplification. Amplification was less frequent in Scarff-Bloom-Richardson grade I ductal carcinomas than in grades 2 and 3. Metastatic carcinomas frequently displayed HER2/neu amplification (6/20 [30%]). Our results support a correlation between HER2/neu amplification and the histologic type and grade of breast cancer. We suggest reexamination of tumors diagnosed as Scarff-Bloom-Richardson grade I invasive ductal carcinomas or lobular carcinomas if the lesion displays HER2/neu amplification to assure the exclusion of a higher grade of lesion or of missed ductal components.

Breast Neoplasms↗

PubMed2002

Chromosome 1p allelic loss by fluorescence in situ hybridization is not observed in dysembryoplastic neuroepithelial tumors.

Differentiation of dysembryoplastic neuroepithelial tumor (DNT) from cystic low-grade oligodendroglioma, particularly in a limited biopsy orfragmented specimen, may be impossible. Research has shown that allelic loss of chromosome 1p is a relatively common finding in oligodendrogliomas. Little is known about chromosome 1p status in DNT. We retrospectively evaluated 14 DNTs for loss of heterozygosity (LOH) on chromosome 1p by fluorescence in situ hybridization (FISH) and compared the results with 1p FISH analysis in 57 low-grade oligodendrogliomas (World Health Organization grade II). The 14 DNTs arose in 8 females and 6 males (mean age, 20.9 years at the time of surgery). All 14 DNTs were 1p intact by FISH analysis. The 57 low-grade oligodendrogliomas arose in 31 males and 26 females (mean age, 43.2 years). LOH on chromosome 1p was present in 31 (54%) of 57 tumors; the remaining 26 tumors were 1p intact. LOH on chromosome 1p is not a feature of DNTs. LOH on chromosome 1p may be a useful differential diagnostic feature (favoring oligodendroglioma) in a subset of cases in which specimen fragmentation or size raises the differential diagnosis of DNT vs oligodendroglioma.

Adolescent↗

PubMed2002

Detection of bcl-2/J(H) translocation by polymerase chain reaction: a summary of the experience of the Molecular Oncology Survey of the College of American Pathologist.

CONTEXT: The t(14;18)(q32;;t6q21) translocation, found in about 85% of follicular lymphomas, brings the bcl-2 gene on 18q21 under control of the immunoglobulin heavy-chain gene transcriptional regulatory elements on 14q32. Detection of this translocation in a clinical sample suspected of containing lymphoma can assist the pathologist in diagnosis and classification of lymphoma. Polymerase chain reaction is a technology that is frequently used to detect the t(14;18)(q32;q21) translocation (bcl-2/J(H)). This article reviews the utility of polymerase chain reaction testing for bcl-2/J(H) detection and summarizes the experience of participants in the Molecular Oncology Proficiency Survey of the College of American Pathologists from 1997 through 2000. OBJECTIVE: To describe current practice and encourage improvement of bcl-2/J(H) testing in clinical laboratories. DESIGN: Retrospective analysis of Molecular Oncology Proficiency Survey data. PARTICIPANTS: Laboratory participants in the College of American Pathology Molecular Oncology Proficiency Survey. RESULTS: Twenty-four well-characterized specimens were sent to participants, of which 6 contained bcl-2/J(H) major breakpoint region translocations. Eight hundred nineteen major breakpoint region and 323 minor cluster region determinations were performed, with an overall correct response rate of 91% and 94%, respectively. No significant difference in correct response could be found for frozen versus paraffin-embedded tissues. Many laboratories did not know their assay sensitivity. CONCLUSION: Overall performance was good; however, there was great variability in the methods reported and lack of knowledge of the limits of detection was common. Continued participation in external quality control programs, such as the Molecular Oncology Survey; dissemination of information that impacts on test performance; and technical recommendations from the molecular diagnostics community are critical for improved testing for bcl-2/J(H).

Chromosomes, Human, Pair 14↗