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E Torlakovic

Publications and source records attributed to E Torlakovic.

At least 19 recordsLinked to original sources
PubMed2005

Simultaneous bilateral breast carcinoma: Histopathological characteristics and CD44/catenin-cadherin profile.

AIMS: Family history of breast carcinoma, multicentric tumor foci in one breast, and in situ lobular carcinoma increase the risk of bilateral breast cancer (BBC), synchronous or metachronous. Synchronous tumors are designated as simultaneous breast carcinoma if they appear at the same time. The CD44 family and cadherin/catenin immunophenotype of this group of BBCs has not yet been evaluated. The aim of this study was to compare clinicopathological characteristics and immunohistochemical profiles of simultaneous BBC and corresponding lymph node metastases in eight patients. METHODS AND RESULTS: In toto 15 primary and 9 metastatic tumors were evaluated. The expression of CD44 variant isoforms, beta-catenin, E, P and N-cadherin were evaluated by immunohistochemistry. Rare types of breast carcinoma were frequent in this group of patients. There were 6 pleomorphic lobular, 5 invasive ductal of usual type, 3 atypical medullary carcinomas, 2 mucinous and one invasive micropapillary carcinoma. The expression CD44v6 was most frequent, followed by CD44v3-10, CD44v5, and CD44v3. CD44v4 was generally not expressed. E-cadherin was expressed in 80% primary tumors, 40% expressed N-cadherin, and 66% expressed P-cadherin. CONCLUSIONS: Generally, simultaneous carcinomas had different morphology and different immunophenotype. Each primary tumor was more similar to its corresponding metastatic tumor than to the contralateral primary tumor.

Adult↗
PubMed2002

Prognostic implications of BCL6 rearrangement in uniformly treated patients with diffuse large B-cell lymphoma--a Nordic Lymphoma Group study.

The purpose of this study was to investigate the prognostic implications of BCL6 rearrangement in a uniformly treated population of patients with diffuse large B-cell lymphoma (DLBCL) and to characterise the relationship between BCL6 rearrangement and prognostic factors. A total of 269 patients with DLBCL entered a randomised trial comparing the chemotherapy regimen CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) to the MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin) regimen. In 44 cases, frozen tissue was available for assessment of BCL6 status by Southern blot analysis. BCL6 was rearranged in six of 43 evaluable cases (14%), and was associated with elevated lactate dehydrogenase (LDH), and a higher patient age. No association between BCL6 status and expression of BCL2, Ki-67 or TP53 was found. Patients presenting with BCL6 rearrangement displayed a weak trend towards better overall and failure-free survival (67 and 67% at 5 years), compared to patients with germline BCL6 (63 and 52%), but the difference was not statistically significant. In accordance with previously published series, the presence of BCL6 rearrangement does not define a prognostically distinct subgroup of DLBCL. Assessment of BCL6 status may, however, be of clinical interest when related to other prognostic variables.

Adolescent↗
PubMed2001

Prognostic significance of histologic grading in patients with prostate carcinoma who are assessed by the Gleason and World Health Organization grading systems in needle biopsies obtained prior to radiotherapy.

BACKGROUND: The current study was conducted to evaluate and compare the impact of two major histologic grading systems on failure-free survival in patients with prostate carcinoma who are treated with definitive radiation. METHODS: Eligible patients for the current study had localized adenocarcinoma of the prostate (T1-4pN0M0, T3/4: 67%, median observation time: 69 months) and were treated with intent-to-cure external radiotherapy between 1989 and 1995. The specimens from 178 patients, obtained by needle biopsies, were reviewed simultaneously by two pathologists assigning World Health Organization (WHO) and Gleason grades. Three-tiered Gleason grouping distributed patients into three groups (those with a score < 7, those with a score of 7, and those with a score of 8--10), whereas two-tiered Gleason categorization distributed patients into two groups (those with a Gleason score of 7A, major 3 + minor 4 patients were added to the group of patients with a Gleason score < 7 and patients with a Gleason score of 7B, major 4 + minor 3 were added to the group of patients with a Gleason score of 8--10). Univariate and multivariate analyses were performed. A P value < 0.05 was considered to be statistically significant. RESULTS: Three-tiered Gleason grouping resulted in a relatively even distribution of the patients (44 patients had a Gleason score < 7, 58 patients had a Gleason score of 7, and 76 patients had a Gleason score of 8--10) whereas 130 patients were determined to have Grade 2 tumors based on WHO criteria. Separating those patients with a Gleason score of 7 (score 3+4 vs. score 4+3) led to the two-tiered Gleason grouping (88 patients in the favorable group and 90 patients in the unfavorable group). The two-tiered Gleason grouping displayed differences with regard to failure-free survival with the lowest P values for all patients and separately for T1/2 versus T3/4 tumors. Together with T category and pretreatment prostate specific antigen, WHO grading, three-tiered Gleason grouping, and two-tiered Gleason grouping resulted in independent parameters in the Cox regression model. The proportional variance estimate confirmed the superior discrimination for survival of two-tiered Gleason grouping. CONCLUSIONS: The equal allocation of patients to subgroups based on the Gleason system helps the clinician to overcome the dilemma of overrepresentation of Grade 2 patients as occurs with WHO grading. The Gleason grading system and, most likely, the two-tiered Gleason grouping appear to result in better prognostic separation of patients referred to radiotherapy for relatively advanced primary tumors. Therefore the authors recommend the routine use of Gleason grading for these patients.

Adenocarcinoma↗
PubMed2001

Cultured anaplastic cell lines as immunocytochemistry controls: a comparison of ThinPrep-processed smears and conventional air-dried cytospins.

Cultured anaplastic cell lines with previously characterized phenotypes are considered to be the best positive controls for immunocytochemistry. We assessed the validity of using anaplastic cell line cytospins as positive controls for immunocytochemistry performed on ThinPrep-processed clinical samples. We compared ThinPrep-processed slides and air-dried cytospins from cultured anaplastic cell lines for intensity and pattern of staining. Also, antigen preservation was assessed over a 3-mo period, using a panel of 16 primary antibodies and 12 anaplastic cell lines. A three-step alkaline phosphatase procedure was used except when in a single instance the EnVision method was employed. If appropriately stored, both preparations showed excellent correlation with no decrease in antigenicity during the 3-mo testing period. ThinPrep-processed slides from clinical samples are ideal for immunocytochemistry, because internal negative controls can be performed for each test. We recommend the use of cytospins for positive controls because of the lower cost.

Antigens, Neoplasm↗
PubMed2001

The transcription factor PU.1, necessary for B-cell development is expressed in lymphocyte predominance, but not classical Hodgkin's disease.

Hodgkin's disease (HD) is a lymphoproliferative disease of predominantly B-cell origin. However, the reasons for the incomplete development of the B-cell phenotype and lack of immunoglobulin expression in classical HD (cHD) have not been fully explained. We examined the expression of PU.1 in HD, an Ets-family transcription factor, which regulates the expression of immunoglobulin and other genes that are important for B-cell development. Immunohistochemistry for PU.1 was performed on 35 cases of cHD and 15 cases of lymphocyte predominance HD as well as 67 non-Hodgkin's lymphomas (NHL). Expression of PU.1 was studied by Western blotting in four cHD-derived cell lines and in five NHL cell lines. We also studied the expression of two additional B-cell transcription factors, B-cell-specific activator protein and Oct-2. Our results show a striking lack of PU.1 expression by neoplastic cells in cHD but not in lymphocyte predominance HD. Our study also confirmed that B-cell-specific activator protein but not Oct-2 is not expressed by cHD. Western blotting showed no PU.1 protein expression in the cHD-derived cell lines, with the exception of one cell line of putative monocyte/histiocyte origin. The lack of PU.1 protein expression in cHD likely contributes to the lack of immunoglobulin expression and incomplete B-cell phenotype characteristic of the Reed-Sternberg cells in cHD.

Blotting, Western↗
PubMed2001

CD34(+) cell enrichment depletes atypical CD30(+) cells from PBPC grafts in patients with HD.

BACKGROUND: European Group for Blood and Marrow Transplantation (EBMT) registry data indicate that patients with relapsed HD given high-dose therapy (HDT), supported with PBPC might have a poorer outcome compared with those given BM. Since this can be due to the infusion of contaminating tumor cells in the PBPC products, we studied the presence of minimal residual disease and tested whether CD34(+) cell enrichment was able to remove atypical CD30(+) cells from PBPC grafts. METHODS: Eighteen HD patients eligible for HDT were included in the study. By the use of immunocytochemistry (ICC), mononuclear cells from BM and peripheral blood (PB) before mobilization, PBPC products and selected CD34(+) fractions were stained using anti-CD30 MAb (Ber-H2) and the APAAP (alkaline phosphatase-anti-alkaline phosphatase) method. Cells scored as atypical CD30(+) cells were large- to medium-sized, with membranous, cytoplasmatic and/or Golgi positivity for CD30. RESULTS: Nine out of 11 BM tested were positive, while 14 of 14 PB and 18 of 18 PBPC contained atypical CD30(+) cells. The total number of atypical CD30(+) cells was significantly higher in PBPC than in the corresponding BM. CD34(+) cell enrichment employing ISOLEX 300I gave a purity and yield of 99.2% (range 97.8-99.7) and 49.6% (range 30.0-78.4), respectively. After HDT a median of 5.8 x 10(6) (range 2.7-20) CD34(+) cells/kg was infused. Neutrophil counts of > 0.5 x 10(9)/L and platelet counts of > 20 x 10(9)/L were achieved at Day 12 (range 10-17) and at Day 10 (range 7-15), respectively. Sixteen of 18 CD34(+) selected products had no detectable atypical CD30(+) cells, while two had a low number. After HDT, the overall survival was 80% and the event-free survival was 69%, with a median follow-up of 24 months (range 1-36). DISCUSSION: We show that contaminating atypical CD30(+) cells in PBPC can efficiently be removed by CD34(+) cell enrichment, and the use of such grafts following HDT gives fast and sustained engraftment.

Adolescent↗
PubMed1999

Uracil mustard revisited.

BACKGROUND: A patient with diffuse large cell lymphoma who had a complete response lasting 35 years following a 3-day course of uracil mustard stimulated a recall review of patients treated with this oral alkylating agent. METHODS: Records of patients treated with uracil mustard between 1958 and 1970 were reviewed. A current histologic review according to the International Formulation was performed when possible. Total doses of uracil mustard were similar to those of mechlorethamine, although there were variations in the dose schedule. RESULTS: Employing criteria used over 25 years ago to evaluate patients' responses, the overall regression rate for 94 non-Hodgkin lymphoma patients was 69.2% (complete response [CR] 23.4%). Of 62 patients with Hodgkin disease, 69.4% responded (CR 9.7%). For 39 patients with chronic lymphatic leukemia, the combined complete and partial response rate was 74% (CR 7.7%). Thrombocytopenia was the primary toxicity. CONCLUSIONS: Uracil mustard is an unmarketed, inexpensive oral alkylating agent that has been effective in the treatment of patients with lymphoma, chronic lymphatic leukemia, and thrombocythemia. Perhaps it should be reevaluated.

Adolescent↗
PubMed1999

Detection of immunoglobulin heavy chain gene rearrangements by polymerase chain reaction analysis on lymph node imprints and fine-needle aspirate smears: a comparison of five different imprint preparations.

Five different preparations of lymph node imprints from 39 patients were studied to determine which preparations are suitable for obtaining interpretable results with polymerase chain reaction (PCR)-based detection of immunoglobulin heavy chain gene rearrangements and whether there are significant discrepancies in the patterns obtained. The sensitivity and specificity of this test for the diagnosis of B-cell lymphoma were assessed. The five imprints were stained with May-Grünwald-Giemsa (MGG) and coverslipped, stained with MGG but not coverslipped, fixed in acetone only, air-dried only, or immunostained, respectively. The efficiency of the PCR was 0% for immunocytochemically stained slides, 87% for air-dried only and air-dried/MGG-stained/coverslipped slides, 95% for air-dried/MGG-stained/not coverslipped slides, and 100% for imprints that were air-dried/acetone-fixed. There was total agreement in results in 87% cases studied. Discrepancies never resulted in false-positive test results. The overall sensitivity was 50%, and specificity was 100%. Based on these results, we have devised guidelines for tissue treatment when only stained slides are available. In a prospective study with 19 fine-needle aspirate specimens, the efficiency of the PCR increased to 100%, and sensitivity improved to 81%.

Biopsy, Needle↗
PubMed1999

High-dose therapy supported with immunomagnetic purged autologous bone marrow in high-grade B cell non-Hodgkin's lymphoma.

From August 1987 to March 1995, 25 patients with high-grade B cell non-Hodgkin's lymphoma (NHL) were treated with high-dose therapy (HDT) followed by bone marrow purged with immunomagnetic beads. At the time of transplantation, 20 patients were in sensitive relapse and five in first complete or partial remission. Ten patients had secondary high-grade NHL transformed from low-grade NHL. The HDT consisted of TBI followed by high-dose cyclophosphamide. All patients engrafted, except for two patients with early treatment-related death. Eleven patients relapsed, of whom nine died of lymphoma, and two are alive in new CR. The estimated event-free and overall survivals at 5 years were 40% and 48%, respectively, with a median follow-up of 48 months (range 1-123). Eight of the tumours contained the translocation t(14;18) at the major breakpoint region (MBR) of BCL-2. In these patients the presence of tumour cells in the bone marrow graft before and after purging were assessed by PCR. Four of five patients infused with non-detectable minimal residual disease in their autografts are in complete remission, while two of three patients reinfused with t(14;18) positive cells after purging, experienced a fast and aggressive relapse. As found by others, our data suggest that reinfusion of tumour-free autografts obtained by efficient in vivo purging using chemotherapy before harvesting, and/or by in vitropurging of the stem cell products, influence the patients remission status after HDT.

Adolescent↗
PubMed1999

Evaluation of lymphoid cell populations in cytology specimens using flow cytometry and polymerase chain reaction.

Differential diagnosis between lymphomas and reactive lymphoid proliferations often requires ancillary techniques and morphologic evaluation. Flow cytometry (FCM) and polymerase chain reaction (PCR) can aid the detection of monoclonal B-cell populations. In the present study, the sensitivity and specificity of these two methods in the study of cytology specimens were compared. Eighty-six cytologic specimens from 81 patients (lymph nodes, solid organs, and body cavities) were evaluated. These specimens were taken from three groups of patients: those who underwent an initial evaluation for suspected lymphoma; those who were previously diagnosed with B-cell lymphoma and were now evaluated for possible disease recurrence; and those who were diagnosed with a nonhematologic malignancy. Histologic diagnosis was available for 51 samples. All samples were tested by FCM for the detection of monoclonality using kappa:lambda ratio and for clonal immunoglobulin heavy chain (IgH) gene rearrangements using a single-round PCR after cytologic evaluation. Tissue morphology, FCM and PCR results, and clinical findings in specimens without histologic diagnosis were correlated. Histologic evaluation (N = 51) revealed 44 specimens with B-cell malignancy. Twenty of the 44 lymphoma specimens (45%) were accurately diagnosed in cytologic smears, 18 (41%) were classified as suspicious of lymphoma, and 6 (14%) were diagnosed as reactive. FCM had superior sensitivity compared with PCR (77% vs. 64%). Fifty-six percent of specimens with B-cell malignancy were FCM+/PCR+, 23% were FCM+/PCR-, 14% were FCM-/PCR+, and 7% were FCM-/PCR-. The combined use of FCM and PCR resulted in a diagnosis of B-cell lymphoma in 41 (93%) of 44 B-cell lymphoma specimens and increased the sensitivity of fine needle aspiration by 48%. Both FCM and PCR aid in the diagnosis of lymphoid lesions in cytology specimens, and both can detect monoclonal B-cell populations that may be interpreted in cytology smears as reactive, even by experienced cytologists. Although FCM had higher sensitivity than PCR test in the present study, their combined use should be considered because of a relatively large number of specimens that were detected as monoclonal only with PCR.

Biopsy, Needle↗
PubMed1998

Demonstration of clonality in neutrophils using FISH in a case of chronic neutrophilic leukemia.

A patient previously diagnosed with chronic neutrophilic leukemia (CNL) was studied using fluorescent in situ hybridization (FISH) to determine clonality of neutrophils. By cytogenetic studies the patient's blood and bone marrow had an 11q14 deletion and were negative for the Philadelphia (Ph) chromosome. FISH was performed on peripheral blood smears using probes for the bcr/abl translocation and a probe for 11q23 (MLL). The patient's white blood cells were negative for the bcr/abl translocation; neutrophils and eosinophils, but not lymphocytes, were monosomic for the 11q23 probe indicating a clonal population within the neutrophil population.

Chromosomes, Human, Pair 11↗
PubMed1997

B-cell gene rearrangement in benign and malignant lymphoid proliferations of mucosa-associated lymphoid tissue and lymph nodes.

The polymerase chain reaction (PCR) with polyacrylamide gel electrophoresis was used to study patterns of immunoglobulin heavy chain (IgH) gene rearrangement (GR) in formalin-fixed, paraffin-embedded specimens of lymphomas and reactive conditions of mucosa-associated lymphoid tissue (MALT) and lymph node. DNA amplification was performed directly on sections obtained from paraffin blocks. Five patterns of PCR products were observed: a single band, two or more discrete bands, smearing, a single band overlying a smear, and two or more bands over a smear. A pure polyclonal pattern (smear) was observed in all of the reactive lymph nodes but in only 15% of cases of Helicobacter pylori (HP) gastritis with lymphoid hyperplasia, 25% of cases of HP gastritis without lymphoid hyperplasia, and 37% of colonic specimens of various types. Patterns consisting of multiple bands with or without background smearing were common in gastritis, colitis, and gastric lymphomas. Single bands or dominant bands were present in all lymph node and salivary gland lymphomas, 12 of 14 cases of gastric lymphoma, and 17 of 20 cases of HP gastritis with lymphoid hyperplasia. These bands were reproducible in deeper sections from the same paraffin block or similar areas sampled in different blocks in all of the lymph node and salivary gland lymphomas, 11 of 12 gastric lymphomas, but only 1 of 17 cases of HP gastritis with lymphoid hyperplasia. Bands were also found in 3 of 20 cases of HP gastritis without lymphoid hyperplasia and 17 of 38 colonic specimens, but these were not reproducible. The complexity of patterns of IgH GR in acquired MALT compared with lymph nodes may be the result of a relative paucity of B-cell clones or preferential proliferation of B-cell clones with a limited area of distribution.

DNA, Neoplasm↗
PubMed1997

Mucin genes expressed by human female reproductive tract epithelia.

Recent characterizations of mucins at the molecular level indicate that at least eight mucin genes are expressed by epithelia of mucosal surfaces. The purpose of this study was to determine whether these cloned mucins, designated MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC6, and MUC7, are expressed by epithelia of the female reproductive tract. Northern blot analysis, in situ hybridization, and immunohistochemistry were performed using RNA and tissue from surgically removed human reproductive tract specimens including endocervix, ectocervix, vagina, endometrium, and fallopian tube. Complementary DNA to the tandem repeat regions of MUCs 1, 2, 3, 5AC, 5B, and 6; oligonucleotides to the tandem repeat regions of MUCs 4, 6, and 7; and antibodies that recognize unique mucin tandem repeats were used. The data demonstrate that the endocervical epithelium expresses five mucin genes: MUCs 1, 4, 5AC, 5B, and 6. The ectocervical and vaginal epithelia express MUCs 1 and 4, although vaginal expression of MUC4 appears patchy. Endometrial epithelium expresses MUC1 and low amounts of MUC6. MUC6 immunoreactivity was detected only is scattered endometrial glands located in the basalis region in specimens from pre- and postmenopausal women. The only mucin detected in the fallopian tube was MUC1. These data indicate that the endocervical epithelium expresses multiple mucin genes and that the stratified epithelia of the ectocervix and vagina also produce mucins that may function in reproductive processes and protection of the reproductive tract tissues.

Base Sequence↗
PubMed1996

Serrated adenomatous polyposis in humans.

BACKGROUND & AIMS: Hyperplastic polyposis clinically resembles adenomatous polyposis and has not generally been considered precancerous. However, since the original description, a number of cases associated with adenocarcinoma have been reported. The aim of this study was to reevaluate patients previously diagnosed with hyperplastic polyposis. METHODS: Pathological analysis of polyps in 6 patients with putative hyperplastic polyposis and 4 with associated carcinoma was compared with classic isolated hyperplastic polyps, adenomas, and solitary serrated adenomas. Immunohistochemical study for the detection of p53 protein, blood groups antigens, including Lewis(a) and Lewis(b), and peanut lectin binding was performed. RESULTS: Polyps in our patients were much more similar to serrated adenomas than to hyperplastic polyps and were characterized by large size, prominent architectural distortion, cytologically atypical nuclei, focal nuclear crowding and nuclear dispolarity, and rare upper zone mitotic figures. The polyps in our patients and control serrated adenomas had a decrease or absence of endocrine cells compared with classic hyperplastic polyps and normal colon and similar immunohistochemical reactivity for p53 and Lewis(a) and Lewis(b) antigens. CONCLUSIONS: Our results indicate that the polyps in our patients are serrated adenomas. Serrated adenomatous polyposis has not been described before and should be distinguished from true hyperplastic polyposis given a possible association with adenocarcinoma in the former group.

Adenocarcinoma↗
PubMed1995

Intracellular bacteria in blood smears in patients with central venous catheters.

The presence of intracellular bacteria in blood smears is usually associated with overwhelming sepsis and an ominous prognosis. Recently, the hematology laboratory at our institution documented this finding in a group of mostly asymptomatic patients. We studied seven adult patients from a tertiary care university hospital in whom intracellular bacteria were found incidentally on routine manual differential cell counts of 100 white blood cells during a 12-month period. A retrospective review of the clinical and laboratory data was performed. All seven patients were immunosuppressed and had central venous catheters in place. The blood samples positive for intracellular bacteria were all catheter derived. Six patients were asymptomatic at the time of bacteria detection, but they had blood cultures that were positive for coagulase-negative Staphylococcus; five of these patients became symptomatic 1 to 14 days after bacteria detection. Bacteremia persisted in five of these six patients until the eventual removal of the catheters. The one symptomatic patient had Pseudomonas aeruginosa bacteremia and died shortly after admission. The finding of intracellular bacteria in routine differential blood cell counts from a central venous catheter blood specimen most likely indicates active infection. We recommend that central venous catheters be removed in such patients, even if the patient is asymptomatic.

Adult↗
PubMed1994

Direct detection of the Philadelphia chromosome in CD20-positive lymphocytes in chronic myeloid leukemia by tri-color immunophenotyping/FISH.

Six patients with previously diagnosed chronic myelogenous leukemia (CML) were studied by a tri-color immunophenotyping/FISH method for direct determination of the Philadelphia (Ph) chromosome in B and T lymphocytes. Two patients had involvement of CD20-positive lymphocytes. CD3-positive lymphocytes in all patients were negative for the Ph chromosome.

Antigens, CD↗