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Emina Torlakovic

Publications and source records attributed to Emina Torlakovic.

27 records · Page 2Linked to original sources

Morphologic reappraisal of serrated colorectal polyps.

The "hyperplastic polyp" is considered a benign lesion with no malignant potential, whereas "serrated adenoma" is a precursor of adenocarcinoma. The morphologic complexity of the serrated adenoma varies from being clearly adenomatous to being difficult to distinguish from hyperplastic polyp, which creates a need for more detailed morphologic analysis of all serrated polyps. We evaluated 24 morphologic variables in 289 serrated polyps from the colon and rectum. Cluster analysis and discriminant analysis were performed. A subset of polyps was immunostained for hMLH1 and hMSH2. Major differences were found between right-sided and left-sided polyps. A distinct group of serrated polyps with abnormal proliferation was identified throughout the colon and rectum. These polyps demonstrated decreased expression of hMHL1 and hMSH2 compared with polyps with normal proliferation. Left-sided serrated polyps with normal proliferation further clustered into three groups: vesicular cell-type, goblet cell-type, and mucin-poor-type. We recommend evaluation of the localization, size, and morphologic features when serrated polyps are included in colorectal carcinogenesis research. Polyps with abnormal proliferation are similar to the polyps in "hyperplastic polyposis" and, because of their decreased expression of hMLH1 and hMSH2, may be the subset of polyps associated with the development of colorectal carcinoma via the microsatellite instability pathway.

Adaptor Proteins, Signal Transducing↗

Immunohistochemical expression of CD23 and CD40 may identify prognostically favorable subgroups of diffuse large B-cell lymphoma: a Nordic Lymphoma Group Study.

PURPOSE: In search for subgroups of diffuse large B-cell lymphoma (DLBCL) with different histogenetic origin and prognosis, as has been described by gene expression profiling, we examined tumor specimens from 125 patients with DLBCL, uniformly treated by either cyclophosphamideAdriamycin-vincristine-prednisone or methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin in a multicenter trial set by the Nordic Lymphoma Group 1989-1994. EXPERIMENTAL DESIGN: Bcl-6, CD10, and CD40 were chosen as markers for a germinal center phenotype, CD23 as a marker of pre/early germinal center origin, and CD138 as a marker for postgerminal center origin. In addition, expression of the apoptotic regulators bcl-2 and bax was analyzed. Immunohistochemical analysis was performed using the EnVision method. RESULTS: CD10 was positive in 51%, bcl-6 in 97%, and CD138 only in 2% of the cases. No prognostic conclusions could be drawn from analysis of these factors. CD40 was positive in 76% of the cases. This group was associated with superior time to treatment failure (P = 0.027) and overall survival (OS; P = 0.0068). By Cox regression analysis, positivity for CD40 was shown to be a prognostic factor for OS, independent of International Prognostic Index. CD23 was positive in 16% of the cases (all CD5 negative and all CD40 positive). This group showed a strong tendency for better OS (P = 0.033). CD40 expression correlated with bax but not with bcl-2 expression. CONCLUSIONS: CD23 and CD40 expression seems to be prognostically favorable in DLBCL. This may be secondary to a germinal center origin or attributable to increased apoptosis via induction of bax and/or enhanced T-cell interaction, resulting in improved autologous tumor response. Confirmatory studies are necessary.

Adult↗

Estrogen and progesterone hormone receptor status in breast carcinoma: comparison of immunocytochemistry and immunohistochemistry.

We evaluated the correlation between histologic and cytologic specimens in the determination of estrogen receptor (ER) and progesterone receptor (PR) status in breast carcinoma and investigated the causes of clinically significant discrepancies. We analyzed 70 immunoassays for ER and 60 for PR from 71 patients with breast carcinoma. Concordance between cytology and histology was 89% for ER and 63% for PR using scores from pathology reports. Concordance between cytology and histology was 98% for ER and 91% for PR using consensus scores (obtained after reevaluation by the team of pathologists). Thirty of 130 (23%) tests had clinically relevant discrepancies, 53% of which were caused by wrong interpretation of cytologic findings, 10% by wrong interpretation of histologic findings, 17% by sampling error and 20% were not available for reevaluation. Wrong interpretation of the results for ER and PR status in cytology was a far more frequent cause of clinically relevant discrepancies than sampling errors. The use of strict criteria is recommended.

Adenocarcinoma, Mucinous↗

Prostate carcinoma expression of estrogen receptor-beta as detected by PPG5/10 antibody has positive association with primary Gleason grade and Gleason score.

The objective of this study was to study the expression of estrogen receptor-beta (ER-beta) in prostatic adenocarcinoma and correlate it with Gleason grade and clinical outcome. Immunohistochemical evaluation was performed on prostate needle biopsies from 53 patients (T1-T3pN0M0). ER-beta and ER-alpha transcripts were also studied by semiquantitative reverse transcriptase polymerase chain reaction in PC-3 and LNCaP prostate carcinoma cell lines. ERbeta was expressed in 93% of adenocarcinomas and was positively associated with primary Gleason grade (P = 0.028 for percentage of positive cells and P = 0.046 using a semiquantitative scale) and Gleason score (P = 0.010 for percentage of positive cells and P = 0.014 using a semiquantitative scale). ER-beta expression in the benign epithelium of prostates with adenocarcinoma was detected in 92% of cases and in the stroma in 47% of cases. A trend for longer time to treatment failure was noted for cases with low ER-beta expression after curatively intended radiotherapy (P = 0.082). PC-3, an aggressive prostate cancer cell line with invasive properties in nude mice, expressed higher levels of ER-beta than LNCaP, a nonmetastasizing cell line, whereas no difference for ER-alpha transcripts could be observed. Our findings suggest that ER-beta, as detected by PPG5/10 antibody, may have a role in the process of dedifferentiation of prostate adenocarcinomas, with higher levels present in less differentiated tumors.

Adenocarcinoma↗

The value of anti-pax-5 immunostaining in routinely fixed and paraffin-embedded sections: a novel pan pre-B and B-cell marker.

Whereas L26 (anti-CD20) is well established as a B-cell marker of high specificity for use in paraffin-embedded tissues and JCB117 (anti-CD79a) is increasingly used, a comparable additional pan-B-cell antibody has hitherto not yet been identified. Here we have studied the use of a novel anti-pan-B-cell marker Pax-5 for use in diagnostic pathology. Pax-5 encodes for BSAP (Pax-5), a B-cell-specific transcription factor, the expression of which is detectable as early as the pro-B-cell stage and subsequently in all further stages of B-cell development until the plasma cell stage where it is downregulated. Pax-5 is essential for B-lineage commitment in the fetal liver, whereas in adult bone marrow this transcription factor is required for progression of B-cell development beyond the early pro-B (pre-BI) cell stage. Among the B-cell genes that are present in early B-cell development and are upregulated by Pax-5 are CD19 and Igalpha (CD79a). We have tested a commercially available anti-Pax-5 antibody (anti-BSAP, clone 24) in a series of 592 routinely fixed and paraffin wax-embedded biopsies, including lymph nodes, bone marrow, and various other organs containing lymphoid tissues. Pax-5 protein (BSAP) was detected in all cases of precursor and mature B-cell non-Hodgkin lymphomas/leukemias. In addition, in 97% of classic Hodgkin lymphomas, Reed-Sternberg cells expressed Pax-5. However, Pax-5 was not detected in any of the multiple myelomas, solitary plasmacytomas, and 4% of diffuse large B-cell lymphomas. Among those diffuse large B-cell lymphomas not expressing Pax-5 were only those with terminal B-cell differentiation. All T-cell non-Hodgkin lymphomas, including ALCL and lymphoblastic lymphomas and leukemias, were negative. There was a strong association between Pax-5 and CD20 expression. We conclude that anti-Pax-5 is an excellent pan-B and pan-pre-B-cell marker. We have found that anti-Pax-5 is superior to anti-CD20 in the diagnosis of pre-B acute lymphoblastic leukemia and classic Hodgkin lymphoma versus ALCL of T and "null" cell type. It was also useful in differential diagnosis between lymphoplasmacytic lymphoma and plasmacytoma. Even though there is an excellent correlation between CD20 and Pax-5 expression, anti-Pax-5 exceeds the specificity and sensitivity of L26 (anti-CD20) because of its earlier expression in B-cell differentiation and its ability to detect all committed B cells, including classic Hodgkin lymphoma.

Antibodies, Monoclonal↗

Follicular pattern of bone marrow involvement by follicular lymphoma.

Five patterns of bone marrow infiltration by non-Hodgkin lymphoma or Hodgkin lymphoma are currently recognized, but a true follicular pattern of bone marrow involvement by follicular lymphoma has not been described. In 260 bone marrow trephine biopsy specimens involved by follicular lymphoma, we identified 12 cases with a follicular pattern of bone marrow involvement. The paratrabecular pattern was not present at all in 9, and it accounted for less than 10% of tumor burden in 3 cases. Malignant follicles in the bone marrow were similar to malignant follicles in the respective lymph nodes. Follicular dendritic cells were identified by immunohistochemical analysis. The true follicular pattern of bone marrow involvement by follicular lymphoma seems to be more frequent in women than in men. It is important to recognize this pattern of follicular lymphoma in the bone marrow because it is possible to misinterpret interstitial lymphoid aggregates as benign in the absence of the more characteristic paratrabecular pattern.

Adult↗

CD34/QBEND10 immunostaining in the bone marrow trephine biopsy: a study of CD34-positive mononuclear cells and megakaryocytes.

CONTEXT: The immunohistochemical detection of CD34 protein using QBEND10 antibody in bone marrow trephine biopsies was shown recently to be a precise method for quantitation of blasts and a possibly useful approach in diagnosis and classification of myelodysplastic syndrome. OBJECTIVES: To evaluate CD34+ cells in bone marrow biopsies with various diagnoses and to assess how counts obtained using this method correlate with blast counts obtained by traditional morphologic evaluation of bone marrow smears. DESIGN: Bone marrow trephine biopsies from 108 adult patients were evaluated by immunohistochemistry using anti-CD34 antibody (QBEND10). CD34+ mononuclear cells were counted and compared with the blast counts in the bone marrow aspirate smears or imprints. CD34+ mononuclear cell clusters and CD34+ megakaryocytes were also recorded. The type of positivity (membranous vs cytoplasmic) and the percentage of CD34+ megakaryocytes were evaluated because the presence of CD34+ megakaryocytes was recently suggested to be present in myelodysplastic syndrome, but not in myeloproliferative disease or nonneoplastic bone marrow. RESULTS: Six of 24 biopsies with partial involvement by non-Hodgkin lymphoma and 5 of 60 biopsies with reactive changes had 5% to 10% CD34+ mononuclear cells and were associated with lymphocytosis and increased hematogones. The CD34+ mononuclear cell clusters were found only in myelodysplastic syndrome and myeloproliferative disease. The CD34+ megakaryocytes were present in all diagnostic groups. CONCLUSION: The number of CD34+ mononuclear cells was often slightly higher than the number of myeloid blasts in the bone marrow smears, probably due to increased hematogones. The presence and the number of CD34+ megakaryocytes do not appear to have diagnostic value, but this finding should be further investigated in relation to clinical parameters.

Antibodies, Monoclonal↗