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Biomedical subjects

H F Mark

Publications and source records attributed to H F Mark.

At least 55 records · Page 3Linked to original sources
PubMed1998

A patient with myelodysplastic syndrome studied by GTG-banding and fluorescent in situ hybridization (FISH).

Molecular cytogenetics using fluorescent in situ hybridization (FISH) is an extremely useful adjunct technique to conventional cytogenetics via GTG-banding. The present paper illustrates the utility of FISH by describing a patient with myelodysplastic syndrome (MDS) who was initially studied using GTG-banding and whose bone marrow was found to be populated with hyperdiploid cells. FISH was used to delineate the numerical and structural chromosomal abnormalities. It revealed the presence of trisomy 8 and determined that the previously unidentifiable marker chromosome was of chromosome 10 origin. Although trisomy 8 is a frequent finding in MDS, the structural chromosomal abnormality of chromosome 10 as reported here is not a common finding.

Aged↗
PubMed1997

Fluorescence in situ hybridization assessment of chromosome 8 copy number in stage I and stage II infiltrating ductal carcinoma of the breast.

A total of 34 cases of infiltrating ductal carcinoma of the breast, not otherwise specified (NOS), were selected, based on the clinical stage of the disease (17 cases stage I and 17 cases stage II). The histologic grade and the DNA content of each tumor were evaluated. Each specimen was analyzed and blinded cytogenetically for the frequency of chromosome 8 copy number using fluorescence in situ hybridization (FISH). Among the informative samples, 16 cases were disomic (47%) and 18 cases (53%) were trisomic. Of the 16 disomic tumors, 13 cases (81%) were classified clinically as stage I disease and 3 cases (19%) were stage II disease. Of the 18 trisomic tumors, 4 cases (22%) were stage I, and 14 cases (78%) were stage II. Microscopically, all trisomic tumors were of high histologic grade and aneuploid when analyzed by flow cytometry. We inferred from these data that a subset of infiltrating ductal carcinomas (NOS) is characterized by chromosome 8 trisomy. This chromosomal abnormality correlates well with other markers that predicate aggressive biological behavior of the tumor. While this observation needs to be further extended, the data suggest that chromosome 8 copy number may be used as a possible marker to identify a subgroup of patients with infiltrating ductal carcinoma associated with a poor prognosis.

Adult↗
PubMed1997

A subset of gestational trophoblastic disease characterized by abnormal chromosome 8 copy number detected by fluorescence in situ hybridization.

The present paper describes the results of research conducted to ascertain whether the report by Mark et al. [1], describing the concurrence of congenital trisomy 8 mosaicism and gestational trophoblastic disease (GTD) in a 42 year-old Gravida IV, Para IV patient was an isolated event. In contrast to other cases described in the literature, the patient described in Mark et al. [1] had no additional confounding chromosomal abnormalities other than trisomy 8. To the best of our knowledge, ours was the only reported case of constitutional trisomy 8 mosaicism associated with gestational trophoblastic disease, a rare gynecological disease entity. The question arises whether there exists a subset of patients with GTD characterized by an abnormal chromosome 8 copy number. The implicit hypothesis is that an abnormal number of chromosome 8 somehow predisposes to cancer. A pilot study of 10 cases of GTD was conducted using fluorescence in situ hybridization (FISH) and a commercial chromosome 8-specific alpha-satellite probe on formalin-fixed, paraffin-embedded patient tissues. Among eight informative cases successfully completed, two cases (25%) were found to be trisomic, when a cut-off point of 10% trisomic cells is adopted. Another two cases (25%) were found to be triploid. The results of our FISH study indicated that an abnormal chromosome 8 copy number found in Mark et al. [1] is unlikely to be an isolated event. Our data are consistent with the hypothesis that a subset of GTD indeed may exist which is characterized by more than two copies of chromosome 8. The present findings corroborate those recently found in breast, prostate, and other cancers.

Adult↗
PubMed1997

Stage I and stage II infiltrating ductal carcinoma of the breast analyzed for chromosome 8 copy number using fluorescent in situ hybridization.

We previously reported the results of 30 informative samples (from a total of 34 specimens gathered) of archival breast cancer tissue, including infiltrating ductal carcinoma (NOS), ductal carcinoma in situ, lobular carcinoma, papillary carcinoma and benign lesions of the breast. The study was conducted using fluorescent in situ hybridization (FISH) and a chromosome 8 alpha-satellite probe. Subsequently, a total of 34 cases of infiltrating ductal carcinoma of the breast (NOS, 17 cases stage I and 17 cases stage II) were studied, again using interphase cytogenetics. The aim of the present study is to confirm and extend the results of our initial study of stage I and stage II disease. Towards this end, 36 additional specimens of formalin-fixed paraffin-embedded breast cancer tissue have been analyzed cytogenetically under blinded conditions for the frequency of abnormal chromosome 8 copy numbers using FISH and the previously described protocol optimized for our laboratory. Of these, 18 were stage I and 18 were stage II. The frequency of trisomy 8 among stage I tumors was found to be 28% (5 out of 18). The frequency of trisomy 8 among stage II tumors was found to be 61% (11 out of 18). These results, while less striking, are consistent with those reported in our initial study of stage I and stage II disease, where the frequencies of trisomy 8 among stage I and stage II tumors were 24% (4 out of 17) and 82% (14 out of 17). These results not only establish that chromosome 8 trisomy is a recurrent finding in breast cancer, but also confirm that a higher frequency of trisomy 8 was observed with a higher clinical stage (stage II) than with a lower stage (stage I). It will be of interest to extend the findings in stage I and stage II breast cancer to other stages as well.

Adult↗
PubMed1997

Translocation 2;19 in a patient with probable relapsed acute myeloid leukemia.

We report the cytogenetic and hematopathologic results from a patient diagnosed with acute myeloid leukemia. Although the initial specimen revealed an apparently normal male karyotype, a translocation, t(2;19)(q21;p13), was detected in the second specimen. It is not clear whether this was a primary or secondary and possibly chemotherapy-induced abnormality. In an extensive search of the recent medical literature database (Medline, 1966 to the present; CancerLit, 1983 to the present, MDX Health Digest, 1988 to the present; HealthSTAR, 1975 to the present, and CINAHL, 1982 to the present), we found no previous report of this specific translocation. This case is of interest not only because of its cytogenetic rarity and its unique clinical features, but also because of the fact that this patient worked in construction management, performing offshore drilling in oil fields for several years, and also worked with plastics and polymer film for about 4 years, although this past history of possible genotoxic exposure may or may not be of relevance. In addition, it is also of interest that one of the translocation breakpoints, 19p13, is apparently identical to that found in the 1;19 translocation associated with pre-B cell acute lymphocytic leukemia.

Adult↗
PubMed1997

Emerging molecular cytogenetic technologies.

Fluorescent in situ hybridization (FISH) as an adjunct technique to conventional banding techniques has been firmly established in the past few years. The many clinical and research applications of FISH include chromosome enumeration using alpha-satellite probes, marker identification, gene mapping and 'chromosome painting' in the delineation of complex structural chromosomal abnormalities. Comparative genomic hybridization (CGH) is a relatively new FISH-based technique which can detect gains and losses of whole chromosomes and subchromosomal regions. Like CGH, which can scan the whole genome without prior knowledge of specific chromosomal abnormalities, spectral karyotyping (SKY) confers on each chromosome a distinct colour to enable identification of even cryptic chromosomal rearrangements. The present paper introduces and summarizes these emerging molecular cytogenetic techniques.

Animals↗
PubMed1996

A Philadelphia chromosome positive CML patient with a unique translocation studied via GTG-banding and fluorescence in situ hybridization.

The Philadelphia (Ph) chromosome was the first consistently occurring chromosome abnormality associated with a single cancer type, chronic myelogenous leukemia (CML). This translocation has since been reported with other chromosome abnormalities. The present report describes a case of Ph chromosome positive CML with a unique complex translocation identified using molecular cytogenetics in addition to routine techniques. GTG-banding revealed abnormalities in at least chromosomes 9, 13, 17, and 22. Fluorescence in situ hybridization (FISH) studies were performed as an adjunct to conventional cytogenetic analyses. Using FISH with the Oncor bcr/abl probe, the Ph translocation previously hypothesized was confirmed. Applying FISH with paired painting probes in various combinations, a complex translocation involving chromosomes 9, 13, 15, 17, and 22 was observed. The results of the GTG-banding and FISH studies were compared with each other and correlated with those of the hematological findings. In an extensive search of the medical literature database (Medline, Health, Cancerlit, Ovid, and CINAHL) spanning nearly three decades (1965-1994), we found no previous report of this specific translocation. Therefore, to the best of our knowledge, this is a unique translocation associated with Ph chromosome positive CML.

Aged↗
PubMed1996

Fluorescent in situ hybridization assessment of chromosome 8 copy number in breast cancer.

Conventional cytogenetics of breast and other solid tumors has been hampered by a number of factors. An analysis of breast tumor tissues was therefore undertaken using fluorescent in situ hybridization (FISH). A total of 34 specimens were analyzed using a chromosome 8-specific alpha-satellite probe. Various approaches were tested and compared. Among 30 informative samples, 11 infiltrating ductal carcinomas, not otherwise specified (NOS), 5 ductal carcinomas in situ, 5 lobular carcinomas, 3 papillary carcinomas, and 6 benign lesions were studied. Of the 11 cases of infiltrating ductal carcinomas (NOS) analyzed, four cases showed 3 signals, one case showed 4 signals, and the rest showed 2 signals. Of the 5 cases of ductal carcinoma in situ samples, 1 showed 3 signals and the other 4 cases showed 2 signals. All cases of lobular carcinomas, papillary carcinomas, and benign lesions showed 2 signals. We inferred from these data that 36% of the infiltrating ductal carcinomas (NOS) were trisomic and 9% were tetrasomic, whereas 20% of the ductal carcinomas in situ were trisomic. All samples from lobular carcinomas, papillary carcinomas, and the benign lesions were disomic. From our preliminary data, it can further be concluded that a subset of breast cancer is characterized by chromosome 8 trisomy. These data are consistent with an ever-increasing database on the association of chromosomal 8 trisomy with other cancers such as leukemia, lymphoma, prostate cancer, ovarian carcinoma, salivary gland tumor, malignant melanoma, desmoid tumors, and recently gestational trophoblastic disease. It is also noted that the ability to analyze formalin-fixed, paraffin-embedded archival material will enable a more comprehensive cytogenetic study of breast cancer than is currently available.

Aged↗
PubMed1996

Cytogenetic analysis of salivary gland type tumors.

Fourteen salivary gland type tumors were analyzed with a combination of conventional cytogenetics via GTG-banding, molecular cytogenetics via fluorescent in situ hybridization, and chromosome morphometry. Nine tumors were benign (eight pleomorphic adenomas and one Warthin tumor) five tumors were malignant (one carcinoma ex pleomorphic adenoma, two adenoid cystic carcinomas including one from the breast, a basal cell adenocarcinoma, and an acinic cell carcinoma). Thirteen specimens grew in tissue culture; the basal cell adenocarcinoma did not grow. The Warthin tumor had a normal karyotype, one pleomorphic adenoma was normal, one had a clone with a missing Y chromosome, and the other pleomorphic adenomas had structural chromosomal abnormalities including the following: translocations between chromosomes 3 and 8, chromosomes 6 and 16, chromosomes 8 and 9, chromosomes 8 and 12, chromosomes 8 and 14, and chromosomes 8 and 21. Of the four malignant tumors with karyotypes, the acinic cell carcinoma and one adenoid cystic carcinoma were normal, the second adenoid cystic carcinoma showed a normal polymorphic variant, whereas the carcinoma ex pleomorphic adenoma demonstrated the following karyotype: 46,XX,dir ins(8;5)(q12;q12q35), add(12)(p13)/46,XX. In conclusion, 66% of the benign tumors and 25% of the malignant tumors demonstrated abnormal karyotypes.

Adenolymphoma↗
PubMed1996

Chronic myeloid leukemia manifested during megakaryoblastic crisis.

We describe a 38-year-old man with a chronic myeloproliferative syndrome characterized by elevated white blood cell and platelet counts and increased blasts in the peripheral blood. Bone marrow aspiration was a "dry tap" and the biopsy specimen was hypercellular with numerous blasts, atypical megakaryocytes, and increased reticulin fibrosis. The blasts exhibited cytochemical reactivity for nonspecific esterase and PAS and immunohistochemically were positive for factor VIII, supporting megakaryoblastic lineage. Cytogenetic studies of peripheral blood revealed the t(9;22)(q34;q11). We interpreted these findings to be most consistent with chronic myeloid leukemia (CML) manifested at the time of megakaryoblastic crisis. Although the initial complete blood count showed leukocytosis and thrombocytosis, the patient subsequently had pancytopenia with clinical and pathologic findings consistent with acute myelofibrosis (AMF). Cytosine arabinoside and etoposide chemotherapy induced remission of the acute leukemia. We conclude that CML infrequently presents itself in megakaryoblastic crisis and that such cases may result in the clinicopathologic syndrome of AMF. The success of chemotherapy in this case also suggests that intensive antileukemic therapy may be useful in other patients with either CML-blast crisis or the clinicopathologic syndrome of AMF.

Adult↗
PubMed1996

A combined cytogenetic and molecular approach for diagnosing delayed puberty.

A phenotypic female aged 15 4/12 years was referred because of delayed puberty and short stature. Chromosomal analysis of peripheral blood leukocytes revealed two subpopulations of cells. The modal cell line was hypodiploid with a missing X chromosome while the other cell line was diploid with one X chromosome and a G-sized chromosome that resembled a Y chromosome in morphology. Subsequent fluorescent in situ hybridization yielded results consistent with the above conventional cytogenetic studies. To provide unequivocal evidence of the Y-chromosome material, molecular analyses using the polymerase chain reaction and various primers were carried out which identified an intact short arm and centromere of the Y chromosome and structurally altered long arms. A laparoscopic bilateral gonadectomy, performed because of the risk of neoplasia, also yielded cells with both 45,X and 46,XY karyotypes. The present report thus illustrates the usefulness of a combined approach for diagnosing delayed puberty.

Adolescent↗
PubMed1996

Laboratory study of breast cancer using conventional and molecular cytogenetics.

Currently, the factors associated with tumor initiation, progression, invasion and metastasis as well as the complex relationship between the genetics of breast cancer are not clearly understood. It is known, however, that the risk of developing breast cancer increases with age, family history of breast cancer, and not bearing a child by age 30. Most breast cancer cases (i.e., greater than 70 percent), however, occur in women who have no identifiable risk factors. The basic methods of treatment (e.g., surgery, chemotherapy and radiation) used today are the same as those used in the 1930s. The current criteria for breast cancer staging include pathologic parameters, such as tumor size and nodal involvement, histologic and cytologic parameters, such as histologic grade, and biologic parameters such as age of the patient, hormone (estrogen and progesterone) receptor status, oncogene activation (e.g., c-myc and HER-2/neu) and tumor suppressor gene inactivation (e.g., p53). Although there is evidence that some of these factors may offer some utility in prognosis, the optimal combination of independent prognostic factors remains elusive. Thus, the need to explore other potential biomarkers is pressing. Laboratory study of breast cancer using conventional and molecular cytogenetics, together with other forms of analysis, will lead to an improved repertoire of biological markers in the future.

Breast Neoplasms↗