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H F Mark

Publications and source records attributed to H F Mark.

At least 37 records · Page 2Linked to original sources
PubMed1999

HER-2/neu oncogene amplification in stage I and stage III ovarian papillary serous carcinoma.

Oncogene amplification has been implicated in the genesis and progression of many cancers. Overexpression of the HER-2/neu proto-oncogene occurs in 20-30% of ovarian epithelial cancers, in which it may be of prognostic significance. Oncogene overexpression is traditionally studied using immunohistochemistry. In this study we used fluorescent in situ hybridization (FISH) to determine HER-2/neu amplification in ovarian papillary serous carcinoma and compared the frequency of amplification in two stages of the disease. Archival tissues from 23 cases of papillary serous ovarian carcinoma (9 cases of stage I and 14 cases of stage III) were analyzed by FISH using a HER-2/neu probe and a chromosome 17 centromere control probe. Determination of the level of amplification was performed according to the standard protocols of the Cytogenetics Laboratory at Rhode Island Hospital. Of the 23 cases successfully analyzed, the frequency of amplification among stage I tumors was 22% (2/9) and the frequency of amplification among stage III tumors was 71% (10/14). These results are significant (P = 0.036). The frequency of stage I tumors among amplified cases was 17% (27/12) and the frequency of stage III tumors among amplified cases was 83% (10/12). This study not only confirms the presence of a subset of ovarian papillary serous carcinoma with HER-2/neu gene amplification, but it also indicates that HER-2/neu oncogene amplification is more likely to be associated with a more advanced stage. Thus, the present data are consistent with the hypothesis that HER-2/neu amplification, similar to HER-2/neu protein over expression, is a prognostic marker of poor outcome.

Adult↗
PubMed1999

Assessment of chromosome 8 copy number in cervical cancer by fluorescent in situ hybridization.

Cervical carcinoma is a malignancy which typically occurs at the transformation zone between squamous and glandular epithelium. The vast majority falls into two histologic types, squamous cell and adenocarcinoma. In an effort to identify a subset of cervical cancer characterized by chromosome 8 trisomy, a biomarker extensively explored by this laboratory, we conducted a study of formalin-fixed, paraffin-embedded materials of cervical cancer. A total of 24 cases of cervical cancer were identified from the archives of the Rhode Island Hospital. Fluorescent in situ hybridization (FISH) using a chromosome 8 centromere enumeration probe was conducted to assess the chromosome 8 copy number in these specimens. Hybridization signals were scored among tumor cells in a blinded fashion. Tumors with >/=15% of cells with three signals were scored as trisomic. Of 24 cases studied, 23 were informative. Of the 23 informative cases, 12 (52.2%) were found to be trisomic. Eleven cases (47.8%) were disomic. The frequency of trisomy in a control chromosome 17 probe was 13.0% (3/23). Selected clinicopathologic characteristics of the tumors were also reviewed. The frequency of trisomy 8 among cases of invasive squamous cell carcinoma was 44.4% (8 of 18 tumors) and that of invasive adenocarcinoma was 80% (4 of 5 tumors). The sole tumor which was both trisomic 8 and amplified for the HER-2/neu oncogene was found to be an invasive adenocarcinoma. While the sample size in this pilot study is not large, the data obtained thus far clearly demonstrate that FISH is an appropriate technique for detecting chromosomal trisomies and that a subset of cervical cancer exists that is characterized by chromosome 8 trisomy. Further exploration of this biomarker is warranted.

Adenocarcinoma↗
PubMed1999

Male infertility associated with a unique 8;22 translocation.

Proper evaluation of male infertility includes a careful history, physical examination, semen analysis, and karyotyping. Molecular cytogenetic analysis may also be necessary to further delineate the karyotype. Following the above approach, we found an apparently unique 8;22 translocation in a male patient with infertility but few other phenotypic manifestations. Delineating the exact genetic basis of infertility is important in view of the most recent advances in reproductive technology such as in vitro fertilization and intracytoplasmic sperm injection. Patients utilizing these emerging techniques need to be properly counseled as to their risks of transmitting these chromosomal abnormalities to their offspring.

Adult↗
PubMed1999

Assessment of chromosomal trisomies in prostate cancer using fluorescent in situ hybridization.

In a previous study, we observed a low frequency of HER-2/neu oncogene amplification in prostate cancer using fluorescent in situ hybridization (FISH). In our continued effort to identify prognostic biomarkers in prostate cancer, we analyzed 74 cases of prostate cancer to assess the presence of chromosomal trisomies in this cohort of patients. Previous results from this laboratory have implicated a role of chromosomal trisomies in various cancers. FISH using a chromosome 7 and a chromosome 8 centromere probe was utilized to study abnormal chromosome copy numbers together with data from a chromosome 17 control. The frequency of trisomy 7 was found to be 58.1% (43 of 74 informative cases), while the frequency of trisomy 8 was found to be 9.5% (7 of 74 informative cases). The frequency of cells showing chromosome 17 trisomy was 18.5% (15 of 81 cases successfully studied). While chromosome 8 trisomy did not seem to play as significant a role here as in other cancers that we studied, the results of chromosome 7 trisomy are consistent with those reported in the literature. Further exploration of selected trisomies as biomarkers in prostate cancer using a larger study sample size is warranted to establish their clinical utilities.

Aged↗
PubMed1999

Occurrence of both t(1;19) and t(8;14) in a patient with chronic lymphocytic leukemia.

While t(1;19) and t(8;14) have been reported singly in pre-B-ALL and Burkitt's lymphoma, respectively, the occurrence of both translocations simultaneously in the same patient is rare. Indeed, a review of the English literature from 1966 to 1999 revealed no case reports with these findings. We report here an 88-year-old patient who was clinically diagnosed to have chronic lymphocytic leukemia and who carried both translocations in her peripheral blood cells. The patient refused to give consent for a bone marrow sample, the preferred tissue for study. The patient's clinical findings are discussed, although the relationship between the clinical information and cytogenetic findings, if any, is not known. Study of additional cases identical to ours will be helpful in determining the correlation, if any, between the patient's phenotype and the occurrence of the two translocations.

Aged↗
PubMed1999

A multimodal approach in the diagnosis of patients with hematopoietic disorders.

Myelodysplastic syndromes (MDS) are a group of relatively ill-defined hematopoietic disorders in which both qualitative and quantitative defects of the hematopoietic cells cause bone marrow dysfunction. With an incidence estimated to be approximately 1 per 100,000 persons per year, MDS mainly affects the elderly. Myelodysplastic syndromes share many features with acute nonlymphocytic leukemia; in fact, a proportion of patients with MDS eventually develop acute myeloid leukemia. To illustrate a multimodal approach in the diagnosis of patients with hematopoietic disorders, we describe a 66-year-old patient with a question of myelodysplastic syndrome, leukemia, and two translocations involving chromosome 10:t(5;10) and t(7;10). These structural rearrangements effectively gave rise to monosomy for part of the long arm of chromosome 5 and for the long arm of chromosome 7. Findings of del(5q) and del(7) in MDS have been reported in the literature. The results of chromosome morphometry, which was conducted to compare the lengths of all relevant chromosome segments, are consistent with the hypothesized chromosomal abnormalities. The investigational technique of fluorescence in situ hybridization (FISH), using both painting and alpha-satellite probes, was used as an adjunct to conventional cytogenetics to further delineate the nature of the chromosome abnormalities observed in the GTG-banded studies. Confirmatory studies utilizing the new technique of spectral karyotyping (SKY) were also carried out. Thus, the multimodal approach of hematopathology, GTG-banding, chromosome morphometry, FISH, and SKY can be very useful for delineating complex cytogenetic cases.

Bone Marrow↗
PubMed1999

Discordant detection of monosomy 7 by GTG-banding and FISH in a patient with Shwachman-Diamond syndrome without evidence of myelodysplastic syndrome or acute myelogenous leukemia.

The myelodysplastic syndromes (MDS) are a group of hematologic disorders commonly affecting elderly persons and often leading to acute myelogenous leukemia (AML). Although rare in children, when MDS does occur, it is frequently part of a congenital disorder such as Shwachman-Diamond syndrome (SDS). Monosomy 7 and/or deletion of part or all of 7q are poor prognostic signs in MDS and AML, although the pathophysiologic relationship between this finding and MDS or AML is unclear. Shwachman-Diamond syndrome is an inherited illness characterized by exocrine pancreatic insufficiency and by congenital neutropenia. Patients with SDS are at increased risk of developing myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). Because monosomy 7 is a poor prognostic sign in MDS and AML, establishing its presence is important. However, different methods of detection of monosomy 7 may lead to different results in some patients. We present the case of a 10-year-old girl known to have SDS, who had a bone marrow aspiration and biopsy done to rule out MDS and AML. By light microscopy, the patient's bone marrow was unremarkable. GTG-banding showed the following karyotype: 45,XX,-C[3]/47,XX,+C[1]/46,XX[45]. Fluorescence in situ hybridization (FISH) was performed with a chromosome 7-specific alpha-satellite probe (D7Z1). Almost all (373 of 376) cells exhibited only one chromosome 7 signal. A second marrow aspiration done 6 months later showed an essentially normal karyotype by GTG-banding. Fluorescence in situ hybridization with the same chromosome 7 probe showed 230 of 250 cells to be monosomic for chromosome 7. A whole chromosome 7 painting probe demonstrated disomy for chromosome 7 in 90 of 90 cells; however, subtle heteromorphism in the centromeric regions of the 2 copies of chromosome 7 was noted in some cells. This case demonstrates that FISH and GTG-banding can give discordant results, that the two should be viewed as complementary technologies, and that both have a place in a full karyotypic analysis. Furthermore, this case demonstrates for the first time that heteromorphism and/or subtle structural abnormalities of chromosome 7, previously associated with MDS and AML, can exist without clinical or morphologic signs of these illnesses. It will be of interest to further study the relationship, if any, between SDS and various structural abnormalities of chromosome 7 in MDS and AML, and to elucidate the molecular mechanisms of pathogenesis, physiology, and treatment of these disorders.

Bone Marrow↗
PubMed1999

HER-2/neu oncogene amplification in cervical cancer studied by fluorescent in situ hybridization.

Oncogene amplification, such as HER-2/neu (C-erbB-2), is a manifestation of genetic instability often associated with the genesis and progression of cancer, including cervical cancer. Oncogene overexpression is traditionally studied using immunohistochemistry. We previously reported studies of oncogene amplification in breast cancer using fluorescent in situ hybridization (FISH), where the data support the hypothesis that HER-2/neu is a prognostic marker of poor outcome. To explore further the possible significance of HER-2/neu oncogene amplification in cervical cancer, we conducted a pilot study of 24 cervical cancer cases. The HER-2/neu FISH probe (Vysis, Inc., Downers Grove, IL) was used to measure gene amplification, with a chromosome 17 centromeric probe as an internal control. Out of 24 cases studied, 23 were informative. Of the 23 informative cases, 2 (8.7%) were found to be amplified. The rest (21 out of 23 or 91.3%) were nonamplified. Both amplified cases were invasive adenocarcinoma. Although the sample size of this pilot study may be somewhat small, the data obtained so far clearly demonstrated that detection of oncogene amplification in cervical cancer is not only feasible but is very sensitive, and suggest that further exploration using a larger sample size may be warranted.

Adenocarcinoma↗
PubMed1999

Conventional and molecular cytogenetic identification of a variant klinefelter syndrome patient with a deleted X chromosome.

We report on the case of a 34-year-old patient with the Klinefelter syndrome and an unusual cytogenetic finding of a deletion involving the short arm of the X chromosome. This was confirmed with fluorescent in situ hybridization (FISH) using an X chromosome-specific whole chromosome painting probe. The patient presented with infertility. The only abnormal physical findings were atrophic testes with azoospermia and elevated levels of follicle-stimulating hormone and luteinizing hormone. This case represents a relatively mild manifestation of the Klinefelter syndrome. Previous reported cases were often associated with more severe phenotypes such as variable degrees of mental retardation and facial dysmorphism, hypothesized as due to the failure of X inactivation. The X inactivation center, located on Xq13, is presumably intact in our patient, who had a deletion involving only the short arm. The mild phenotype observed in our patient was found to be consistent with the conventional and molecular cytogenetic findings.

Adult↗
PubMed1998

Fluorescence in situ hybridization analysis of single-cell trisomies for determination of clonality.

Conflicting data currently exist pertaining to the significance of single-cell trisomies found in a 20-cell cytogenetic analysis of hematologic malignancies. In order to determine the clonality of the numerical abnormalities found in these cases, we performed a retrospective study on a cohort of patients previously analyzed by GTG-banding at Rhode Island Hospital, from July 1, 1990 to November 30, 1996. Fluorescence in situ hybridization (FISH) was performed using chromosome enumeration probes on previously fixed bone marrow and, in some cases, peripheral blood slides from patients identified to have single-cell trisomies of selected chromosomes in 20-cell routine GTG-banded analyses. We seek to determine whether the single cell trisomies represent random nonclonal events or "the tip of an iceberg." The results of the present study indicate that a single unifying answer to the above question does not exist. While some cases are apparently random events as predicted by chance, other cases appear to represent "the tip of an iceberg." It is therefore important for cancer cytogeneticists to interpret the results of each patient on a case-by-case basis and to formulate the most optimal strategy for follow-up in the particular case under study.

Adolescent↗
PubMed1998

Sequential flow cytometry and fluorescence in situ hybridization for the study of formalin-fixed, paraffin-embedded breast cancer cells.

Both flow cytometry and fluorescence in situ hybridization (FISH) are useful techniques in the analysis of cancer tissues. When the two are used in the study of the same specimens, they are usually performed in parallel, separately. This is problematic where there is a scarcity of material, making completion of both studies impossible. Fluorescence in situ hybridization procedures that will utilize excess material discarded from flow cytometry would be advantageous. The present report describes an optimized protocol for performing sequential flow cytometry and FISH using formalin-fixed paraffin-embedded archival material. Although breast cancer tissues were used in this initial study, the protocol is applicable to other cancer tissues as well.

Breast Neoplasms↗
PubMed1998

Trisomy 10 in leukemia.

Previous studies had raised questions about whether the relatively rare finding of trisomy 10 in leukemia is nonrandomly associated with a specific immunophenotype or ethnic origin. To shed light on the above questions and to obtain additional clinical and pathologic information on this unique class of leukemic patients, we conducted a retrospective study of leukemia cases at our laboratory from July 1, 1990, to July 31, 1996. The results not only support the rarity of trisomy 10, but they also reject the hypotheses that all trisomy 10 cases are CD7-positive, or found in Orientals.

Acute Disease↗
PubMed1998

Fluorescent in situ hybridization detection of HER-2/neu gene amplification in rhabdomyosarcoma.

Embryonal rhabdomyosarcoma is the most common malignant soft-tissue tumor in childhood, comprising 45-50% of childhood sarcomas. Cytogenetic studies of this tumor are rare. In view of the paucity of cytogenetic data on this cancer and based on the finding of HER-2/neu gene amplification in a number of cancers that was detected mostly using the traditional technique of immunohistochemistry, we decided to conduct a pilot study to investigate whether HER-2/neu gene amplification in this tumor can be detected using the newer technique of fluorescent in situ hybridization (FISH). Archival tissues of rhabdomyosarcoma were retrieved and FISH using an HER-2/neu probe was undertaken on formalin-fixed paraffin-embedded tissue sections using a protocol optimized for our laboratory at Rhode Island Hospital. Out of 9 cases of rhabdomyosarcoma studied to date, 1 case clearly showed HER-2/neu gene amplification. Thus, FISH is a sensitive technique suitable for the detection of oncogene amplification and the delineation of tumor heterogeneity in this tumor. Future experiments utilizing additional specimens from our centers as well as from other laboratories will be needed to extend the finding in the present pilot study.

Child↗
PubMed1998

Fluorescent in situ hybridization for identifying cytogenetic abnormalities in inadequate and suboptimal specimens.

Conventional cytogenetic analysis is often hampered by its dependency on the evaluation of dividing cells. When the mitotic index is low, or the cytogenetic preparation suboptimal, an accurate diagnosis often cannot be achieved using standard GTG banding. Molecular cytogenetics using fluorescent in situ hybridization (FISH) can be extremely useful in such a situation because it can be performed on nondividing interphase nuclei, and can usually be carried out on existing slides without requiring an additional specimen. The present paper presents two case histories to illustrate the utility of FISH in the clinical setting.

Aged↗