PubMed Health⌕ Search

Biomedical subjects

K Offit

Publications and source records attributed to K Offit.

88 records · Page 5Linked to original sources

Immunohistochemical, molecular, and cytogenetic analysis of a consecutive series of 20 peripheral T-cell lymphomas and lymphomas of uncertain lineage, including 12 Ki-1 positive lymphomas.

Although several independent series of non-Hodgkin's lymphomas (NHLs) have been subjected to cytogenetic studies or analyses of lineages by assaying for clonal immunophenotypes and clonal rearrangements affecting immunoglobulin (IG) and T-cell receptor (TCR) genes, no published reports exist of series of non-B-cell NHLs on which cytogenetic, immunohistochemical, and IG and TCR gene rearrangement studies have been undertaken together. Among 343 NHLs ascertained prospectively between January 1984 and December 1988 at the Memorial Sloan-Kettering Cancer Center, 278 cases with clonal chromosome abnormalities were identified. Of the latter, 20 were non-B-cell NHLs, which in turn comprised 15 peripheral T-cell lymphomas (PTCLs) and 5 lymphomas of uncertain lineage (LULs). The LULs either were biogenotypic, had discordant immunophenotype and immunogenotype, or showed no evidence of B-cell, T-cell, or histiocytic derivation. Of the 15 PTCLs, eight expressed the Ki-1 antigen and four of these had translocations involving the band 5q35 [t(5q35)]. Of the five LULs, four expressed the Ki-1 antigen and one of these had a translocation involving band 5q35. Previous studies have associated t(5q35) with Ki-1 positive NHLs characterized histologically by a pleomorphic diffuse large cell morphology. In our series of 12 Ki-positive non-B-cell NHLs, five (42%) had a 5q35 translocation. They were histologically indistinguishable from the subset without the translocation. The frequent lineage uncertainty exhibited by Ki-1 positive NHLs of similar histology and cytogenetic abnormalities suggests their derivation from an early uncommitted lymphoid cells.

Antigens, Differentiation↗

Ki-1 antigen expression defines a favorable clinical subset of non-B cell non-Hodgkin's lymphoma.

Immunohistochemical and immunophenotypic analyses were performed on 278 cases of karyotypically abnormal non-Hodgkin's lymphoma (NHL). Excluding cases of lymphoblastic lymphoma or mycosis fungoides, 20 cases showed evidence of non-B cell lineage. T cell lineage was proven by genotypic and immunophenotypic analyses in 15 of the 20 cases; five were of ambiguous lineage. All of the non-B lineage cases were of diffuse histology with a large cell component (DLCL). Twelve cases expressed the Ki-1 antigen; five of these cases also demonstrated a translocation with a break at 5q35. Patients with Ki-1 positive DLCL and t(5q35) had a younger median age compared with non-B cell DLCL without t(5q35). The Ki-1 positive patients had a higher frequency of skin involvement and lower incidence of bone marrow involvement compared with Ki-1 negative DLCL. Survival analysis was performed on 86 cases of B cell DLCL and 18 cases of non-B cell DLCL which were serially ascertained prior to receiving cytotoxic chemotherapy. Median duration of complete remission was significantly longer in the B cell compared with the non-B cell DLCL groups; there was only a trend for decreased overall survival in the non-B cell group. Among the subset of non-B cell lymphomas, overall survival of patients with Ki-1 expressing DLCL was significantly longer than those with Ki-1 negative DLCL, who had a median survival of less than a year. These results show that immunophenotypic, immunohistochemical, and cytogenetic markers can define subsets of patients with non-B cell lymphomas with differing clinical characteristics and outcome.

Adolescent↗

t(3;22)(q27;q11): a novel translocation associated with diffuse non-Hodgkin's lymphoma.

Of 187 specimens of non-Hodgkin's lymphoma and four hyperplastic lymphoid proliferations with clonal chromosome abnormalities ascertained serially over a 4 1/2-year period, nine cases with t(3;22)(q27;q11) were identified. Seven of the lymphomas were diffuse tumors, predominantly large cell type. The eighth tumor, a follicular small cleaved cell lymphoma, exhibited a t(3;22) and a t(14;18)(q32;q21). The ninth case was a lymph node from a human immunodeficiency virus-positive patient which showed atypical hyperplasia. Overall survival of t(3;22) diffuse lymphoma patients was not different from that of patients with abnormal karyotypes without t(3;22). The t(3;22) diffuse tumors studied showed a disproportionate frequency of lambda light chain on their cell surfaces, a finding similar to that observed in t(8;22)(q24;q11) Burkitt's lymphomas. Our results indicate that the t(3;22)(q27;q11) is the third most common recurring translocation in diffuse non-Hodgkin's lymphoma.

Adult↗

Leukemic differentiation of a mediastinal germ cell tumor.

The biological basis for acute leukemia associated with mediastinal germ cell tumors has remained unexplained due to lack of critical data that would illuminate the genetic relationship between the two tumors in a given patient. Here we present results of serial cytogenetic investigations on the pretreatment and posttreatment mediastinal yolk sac tumor and immature teratoma biopsies and two separate leukemic bone marrow aspirates from a patient who developed acute nonlymphocytic leukemia 11 months after the initial diagnosis of the germ cell tumor. Presence of an i(12p) in all tumor clones and trisomy 21 in one clone in the posttreatment mediastinal tumor and all leukemic clones establishes the common origin of all tumor clones and shows that in this case the leukemia was derived from the malignant germ cell clone.

Adult↗

Nonrandom chromosomal aberrations are associated with sites of tissue involvement in non-Hodgkin's lymphoma.

In an effort to assess the utility of pretreatment cytogenetics as indicators of sites of involvement by lymphoma, clinical and cytogenetic correlations were performed on 133 consecutive specimens derived from 130 patients with non-Hodgkin's lymphoma. Nonrandom chromosomal aberrations detected at the time of diagnosis were associated with sites of clinical involvement presenting initially or during the progression of the lymphoma. Statistically significant associations included translocation breaks involving the chromosomal region 1p32-36 and bone marrow involvement, chromosome 14 abnormalities including breaks at 14q22-24 and splenic involvement, chromosome 9 abnormalities and pulmonary involvement, and monosomy 11 and bone involvement. A significant correlation was also observed between breaks involving the region 6q22-24, detected during the course of disease, and bone marrow involvement by lymphoma. The relationship of the sites of nonrandom chromosomal breakage reported here to known cellular oncogenes and implications to concepts of tumor evolution and spread are discussed.

Bone Marrow↗

Cytogenetic and molecular genetic analysis of abnormal cells in Hodgkin's disease.

Eleven tumors from ten patients with Hodgkin's diseases (HD) were characterized by histologic, cytogenetic, immunophenotypic, and genotypic studies. Cell surface markers for lymphocyte antigens did not show clonal excess. Five tumors showed the presence of karyotypically abnormal cells, but no common abnormalities were found. The remaining six tumors showed normal karyotypes. Ten tumors were analyzed for gene rearrangements with probes for IgJH, IgCk. IgC lambda, and TCR-beta genes. The IgJH probe detected a minor clonal population (about 5%) in one tumor with abnormal karyotype; three tumors with abnormal karyotypes showed germline genotype. In contrast, four of the six tumors with normal karyotypes showed rearrangements in IgJH (one tumor) and in C-lambda (three tumors) genes. The pattern of gene rearrangement observed in these tumors did not obey the hierarchy described in B-cell differentiation. These results suggest that B-cell lineage cannot be attributed unequivocally to the clonal populations in HD.

Adolescent↗

18q21 rearrangement in diffuse large cell lymphoma: incidence and clinical significance.

Cytogenetic, molecular genetic and clinical information was collected for 102 cases of diffuse large cell lymphoma (DLCL) ascertained in a diagnostic laboratory over a 3-year period. Nineteen cases showed evidence of either a t(14;18) or a rearrangement of one of three genomic probes for breakpoints at 18q21. Clinical and histologic evidence of transformation from follicular lymphoma or chronic lymphocytic leukaemia was available in six cases. Except for age, prognostic clinical variables (LDH, stage, extranodal involvement) were similar between the 18q21 rearranged patients and DLCL patients without 18q21 rearrangement. At a median follow-up in excess of 2 years for both groups, there was no difference in overall survival between the 18q21 rearranged group compared to DLCL patients lacking this genetic abnormality. The median disease-free survival for the 18q21 rearranged group, however, was significantly shorter and survival in partial remission longer. The propensity for extended survival of the 18q21 rearranged DLCL patients with residual or recurrent disease resembled the clinical behaviour of nodular lymphoma patients with t(14;18). These results suggest that cytogenic or molecular genetic identification of a chromosome 18q21 translocation may be of prognostic significance in the analysis of treatment protocols for patients with DLCL.

Adult↗

Molecular analysis of breaks in BCL-1 proto-oncogene in B-cell lymphomas with abnormalities of 11q13.

The t(11;14)(q13;q32) is a recurring translocation that occurs infrequently but non-randomly in B-cell chronic lymphocytic leukemia, B-cell non-Hodgkin's lymphoma, and multiple myeloma. The putative oncogene BCL-1 located at the chromosomal band 11q13 has been cloned previously from a B-cell CLL with t(11;14). We studied the molecular structure of the BCL-1 gene in eight B-cell NHL tumors that exhibited a break at 11q13. The cytogenetic changes in these tumors were t(11;14) in three, t(1;11;14)(q32;q13;q32) in two and dup(11)(pter----q23::11q13----ter) in three. The BCL-1 gene was found to have rearranged in two tumors. By Southern blot analysis of single and double digested DNA from placenta and from the tumors, we mapped the breakpoint in BCL-1 to a 0.5 kb Pst-I-HindIII restriction fragment which was approximately 2kb away from the sites of previously mapped breakpoints. Sequential hybridization of Southern blots of these tumors with different immunoglobulin probes (for J region, Cu, Su) and BCL-1 probe identified co-migrating fragments with Su probe after BamHI restriction digestion. These results demonstrate that translocation breaks in the BCL-1 gene are not clustered in a short stretch of DNA at 11q13, and that the translocation related breaks in the immunoglobulin heavy chain can occur outside the joining region. The implications of these observations to the genesis of chromosomal translocations during B cell development are discussed.

B-Lymphocytes↗

Intermediate- to high-grade histology of lymphomas carrying t(14;18) is associated with additional nonrandom chromosome changes.

We describe additional nonrandom chromosome abnormalities in 18 cases of intermediate- to high-grade non-Hodgkin's lymphoma (NHL) bearing t(14;18) that were ascertained in a prospective cytogenetic study of all lymphomas seen at Memorial Hospital during the period January 1, 1984, to December 31, 1986. These included seven cases that had histological evidence of transformation from a lower grade and 11 that lacked such evidence. The most common of the additional changes seen in both groups affected chromosomes 6 and 7 and comprised the loss of chromosome 6 or del(6q) and the presence of more than two copies of chromosome 7 or duplication of 7q. Changes affecting these two chromosomes were less frequent in low-grade lymphomas with t(14;18) as well as in lymphomas lacking the translocation. These data suggest that common cytogenetic mechanisms underlie expression of high-grade histologies by lymphomas carrying t(14;18). In addition, they may serve as indicators of transformation when encountered in low-grade lymphomas with t(14;18).

Adult↗

Monoclonal hypergammaglobulinemia without malignant transformation in angioimmunoblastic lymphadenopathy with dysproteinemia.

A patient with angioimmunoblastic lymphadenopathy with dysproteinemia had a monoclonal IgG hypergammaglobulinemia. In contrast to previous reports, the development of a monoclonal paraprotein in the setting of angioimmunoblastic lymphadenopathy with dysproteinemia did not herald a transformation to malignancy. The patient improved clinically and the monoclonal gammopathy disappeared when the patient was treated with prednisone. The relationship of these findings to current concepts regarding the cause of angioimmunoblastic lymphadenopathy with dysproteinemia is discussed.

Blood Protein Disorders↗

Decision-making about genetic testing among women at familial risk for breast cancer.

OBJECTIVE: Recent identification of the breast-ovarian cancer susceptibility gene BRCA1 and the breast cancer susceptibility gene BRCA2 have raised the possibility of clinical genetic testing for breast cancer susceptibility. This study examined decision-making about future susceptibility testing among women at familial risk for breast cancer. Based on the transtheoretical model, it was hypothesized that readiness to undergo testing would be related to the ratio between the perceived advantages (pros) and disadvantages (cons) of learning one's susceptibility status. METHODS: Seventy-four women with one or more first-degree relatives with breast cancer were recruited before a routine mammogram. Participants completed measures assessing readiness to undergo testing, perceived pros and cons of testing, and perceived breast cancer risk. Family history data was used to calculate empiric genetic risk of developing breast cancer. RESULTS: Forty-six per cent of participants planned to seek genetic testing as soon as possible, 35% planned to seek testing in the future, and 19% did not plan to seek testing. As expected, greater readiness to undergo testing was associated with a positive decisional balance (pros > cons). Older age and greater perceived risk (but not empiric risk) also were associated with greater readiness. CONCLUSION: The readiness of many women to seek breast cancer susceptibility testing can be attributed, in large part, to their perceptions that the advantages outweigh the disadvantages. Examination of these perceptions suggests that notification of carrier status may have significant effects on women's psychological well-being and breast cancer surveillance and prevention behaviors.

Adult↗

Insurance reimbursement for risk-reducing mastectomy and oophorectomy in women with BRCA1 or BRCA2 mutations.

PURPOSE: Risk-reducing surgery is an important option for women with BRCA1 and BRCA2 mutations. There are reports in the literature that insurance reimbursement for these procedures varies greatly. Because health insurance coverage significantly affects medical decision-making, current information regarding reimbursement practices of third-party payers is needed. METHODS: Retrospective study of hospital billing records of 38 women with documented BRCA1 or BRCA2 mutations who underwent either a risk-reducing mastectomy or a risk-reducing oophorectomy between March 1, 1997, and July 30, 2000. RESULTS: Complete billing and reimbursement information was available for 35 women undergoing a total of 39 risk-reducing surgeries. A total of 38 of 39 (97%) risk-reducing surgeries were covered in full, less applicable coinsurance and deductibles. The rate of insurance reimbursement did not vary with type of insurance, personal history of cancer, or type of procedure. CONCLUSION: Insurance carriers reimbursed the vast majority of BRCA mutation carriers undergoing risk-reducing surgery.

Adult↗

Molecular analysis of structural chromosome changes affecting chromosome band 11q23.

Involvement of the ets-1 proto-oncogene located at chromosome band 11q23 was studied in six tumors and in a congenital chromosome abnormality affecting the 11q23 region, in order to determine whether the breakpoint of these rearrangements was identical at the molecular level. In multiple restriction digestions a 5.4 kb EcoRI genomic probe of the c-ets-1 gene did not detect rearrangements in any of these samples. Thus, in these tumors the break in DNA was not within the domain of c-ets-1 recognized by this probe. However, after digestion with XbaI enzyme the probe detected a 2.4 kb polymorphic allele in placental DNA. One tumor DNA sample showed homozygosity for this polymorphic allele. In order to determine the frequency of this polymorphic allele, DNA from 50 additional tumors and from the blood of nine healthy donors was analyzed. DNA from one tumor showed homozygosity for the polymorphic allele. In the 67 DNA samples studied, 17.9 per cent were heterozygous for the polymorphic site and 3 per cent were homozygous for the polymorphic site. Thus, the overall frequency of the polymorphic allele in these samples was 0.111.

Adolescent↗