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Lawrence M Weiss

Publications and source records attributed to Lawrence M Weiss.

35 records · Page 2Linked to original sources
PubMed2004

Promoter hypermethylation and protein expression of the p16 gene: analysis of 43 cases of B-cell primary gastric lymphomas from China.

The p16 (CDKN2a/INK4a) gene is an important tumor-suppressor gene, involved in the p16/cyclin-dependent kinase/retinoblastoma gene pathway of cell cycle control. The p16 protein is considered to be a negative regulator of the pathway. Promoter hypermethylation resulting in inactivation of the p16 gene has been found in various hematopoietic malignancies, including non-Hodgkin's lymphoma, and may play a role in transformation/clinical aggressiveness of those tumors. However, the p16 protein expression in primary gastric lymphoma has not been studied. In this study, we characterize protein expression and promoter hypermethylation of the p16 gene in B-cell primary gastric lymphomas from China. In all, 43 cases of B-cell primary gastric lymphoma were investigated. They consisted of 24 (56%) cases of diffuse large-cell lymphoma, 12 (28%) cases of extranodal marginal zone lymphoma, six (14%) cases of extranodal marginal zone lymphoma with large-cell transformation and one (2%) case of follicular lymphoma. Loss of p16 protein expression was found in 34 (79%) out of 43 cases, while the remaining nine (21%) cases showed positivities for the p16 protein. All 43 cases were further characterized by methylation-specific polymerase chain reaction (PCR) to analyze p16 promoter hypermethylation status. In total, 11 (26%) of 43 cases were positive for p16 promoter hypermethylation. Among those, 10 (30%) out of the 33 cases negative for the p16 immunostaining showed promoter hypermethylation, whereas only one (10%) out of the 10 cases that were positive for the p16 immunostaining displayed promoter hypermethylation. Of the 43 cases, 30 had limited pathologic data at the time of resection. Primary gastric lymphoma involved extragastric sites (lymph node or liver) in 17 (57%) of 30 cases, while the remaining 13 (43%) cases were only limited to the stomach. Loss of p16 protein expression was found in 14 (82%) of 17 cases with extragastric involvement and in 11 (85%) of 13 cases without such involvement. In conclusion, loss of p16 protein expression is frequent in those B-cell primary gastric lymphomas and approximately one-third of such loss correlated with promoter hypermethylation. Despite limited pathologic data, loss of p16 protein expression appears not to be correlated with extragastric involvements.

Adolescent↗
PubMed2004

KSHV/HHV8-associated lymphoma simulating anaplastic large cell lymphoma.

We report a unique, previously undescribed case of KSHV/HHV8-associated lymphoma in a 49-year-old HIV-seropositive patient. The cervical lymph node-based lymphoma displayed distinctive characteristic features of preferential sinusoidal infiltrate and anaplastic cellular morphology, closely resembling classic anaplastic large cell lymphoma of the WHO classification both histologically and immunophenotypically. Paraffin immunohistochemical study showed that the lymphoma cells were strongly positive for KSHV/HHV8 latency-associated nuclear antigen, and PCR analysis confirmed the presence of KSHV/HHV8 infection. Epstein-Barr virus in situ hybridization was negative. Molecular study clearly demonstrated B-cell lineage with immunoglobulin heavy and kappa light chain gene rearrangements. This case may add to the spectrum of the heterogeneous category of KSHV/HHV8-associated B-cell lymphomas.

AIDS-Related Opportunistic Infections↗
PubMed2004

Adrenocortical oncocytic tumors: report of 10 cases and review of the literature.

Ten additional adrenocortical oncocytic tumors are presented: 2 benign oncocytomas, 4 borderline oncocytomas of uncertain malignant potential, and 4 oncocytic carcinomas. Histologically all tumors were entirely or predominantly composed of oncocytes. Immunohistochemically all tumors were immunoreactive for mitochondrial antigen mES-13. Electron microscopy was performed in 8 cases and was confirmatory of the oncocytic cell change. The morphologic parameters of the Weiss system, considered to be predictive of the biologic behavior of conventional (nononcocytic) adrenocortical tumors, are reviewed in the context of their possible application to the oncocytic tumor variant. Proposed major criteria (high mitotic rate, atypical mitoses, venous invasion) and minor criteria (large size and huge weight, necrosis, capsular invasion, sinusoidal invasion) in distinguishing malignant tumors are discussed, and definitional criteria (predominantly cells with eosinophilic and granular cytoplasm, high nuclear grade, diffuse architectural pattern) in common with all types of oncocytic tumors are outlined. The authors' proposed working rules for diagnostic categorization of oncocytic adrenocortical tumors are defined, with the presence of 1 major criterion indicating malignancy, 1 to 4 minor criteria indicating uncertain malignant potential (borderline), and the absence of all major and minor criteria indicative of benignancy. Using these criteria, the diagnosis of malignancy was straightforward in 3 of the 4 cases designated as oncocytic carcinoma (presence of at least 2 major criteria and all the minor criteria), while in 1 case the original diagnosis of benign oncocytoma was reversed to malignant following critical review of the original pathologic material after local tumor recurrence. Tumor recurrence occurred in 2 carcinomas at 8 and 20 months, respectively, and was followed in 1 case by the patient's death. The third patient expired at 6 months from unrelated causes, and the fourth patient is free of disease at the relatively short follow-up interval of 6 months. Regarding the 4 patients with borderline tumors, all are alive with no evidence of disease, with follow-up ranging from 10 to 61 months (mean 38.7 months). The 2 benign tumors have a follow-up of 25 and 30 months, respectively. Diagnostic difficulties are delineated and a complete review of the literature on this topic has also been performed.

Adenoma, Oxyphilic↗
PubMed2004

Differential expression of MUC1, MUC2, and MUC5AC in carcinomas of various sites: an immunohistochemical study.

We studied immunohistochemical expression of MUC1, MUC2, and MUC5AC in 194 carcinomas of different primary sites to determine whether differential expression patterns could be used to distinguish different carcinomas. MUC1 was expressed by most (except adrenocortical and hepatocellular carcinomas). MUC2 was expressed infrequently (positive immunoreactivity primarily in tumors of gastrointestinal origin). MUC5AC was expressed by most pancreatic ductal and endocervical adenocarcinomas and a variable number of tumors of the gastrointestinal tract. A MUC1+/MUC2-/MUC5AC- immunophenotype was observed in most breast, lung, kidney, bladder, endometrial, and ovarian carcinomas; MUC1+/MUC2-/MUC5AC+ was characteristic of pancreatic ductal adenocarcinomas and cholangiocarcinomas. Adrenocortical and hepatocellular carcinomas were negative for all mucins. Carcinomas of gastrointestinal origin exhibited variable expression of each mucin examined and no consistent immunoreactivity pattern. Many carcinomas can exhibit distinct MUC1, MUC2, and MUC5AC expression patterns, which might be valuable diagnostically in specific settings (eg, distinguishing cholangiocarcinoma from hepatocellular carcinoma or renal from adrenocortical carcinoma). However the overlapping and heterogeneous patterns of MUC1, MUC2, and MUC5AC expression observed in many tumors, particularly those of gastrointestinal origin, preclude use of these markers in the routine immunohistochemical assessment of carcinomas of an unknown primary site.

Biomarkers, Tumor↗
PubMed2004

Immunohistochemical characterization of signet-ring cell carcinomas of the stomach, breast, and colon.

We studied the immunophenotype of signet-ring cell carcinoma (SRCC) of the stomach (30 cases), breast (21 cases), and colon (9 cases) with the following expression patterns: (1) breast: consistent, MUC1 (21 [100%]), cytokeratin (CK) 7 (20 [95%]), estrogen receptor (ER; 17 [81%]); infrequent, E-cadherin (6 [29%]), MUC2, MUC5AC, CK20 (1 [5%] each); negative, CDX2 and hepatocyte paraffin 1 (Hep Par 1; 0 [0%] each); (2) gastric: frequent, CDX2 (27 [90%]) and Hep Par 1 (25 [83%]); variable, E-cadherin and CK20 (17 [57%] each), MUC2 and MUC5AC (15 [50%] each), MUC1 (5 [17%]); negative, ER (0 [0%]); and (3) colon: frequent, MUC2 (9 [100%]), CDX2 and MUC5AC (8 [89%] each); infrequent or negative, MUC1 (3 [33%]), Hep Par 1 (2 [22%]), ER (0 [0%]). Immunohistochemical staining distinguished breast from gastric SRCC (ER, MUC1, Hep Par 1, CDX2) and colon SRCC (ER, CDX2, MUC2, and MUC5AC). Gastric and colon SRCCs showed a similar staining pattern for antibodies tested except for Hep Par 1 and CDX2 (gastric, 83% Hep Par 1 positivity and heterogeneous, weak, patchy CDX2 nuclear staining; colon, 22% Hep Par 1 positivity and homogeneous, strong, diffuse CDX2 nuclear staining). About half of the cases of gastric SRCC expressed MUC2 and MUC5AC, whereas virtually all cases of colon SRCC expressed them.

Biomarkers, Tumor↗
PubMed2004

CD163: a specific marker of macrophages in paraffin-embedded tissue samples.

Paraffin-section immunohistochemical analysis was performed using a monoclonal antibody against CD163 to evaluate the antibody's usefulness in identifying cells of monocyte/macrophage lineage in normal and neoplastic conditions. Normal human tissue samples and samples from 211 hematopoietic disorders and 115 nonhematopoietic neoplasms were examined. The distribution of KP1 and PG-M1, monoclonal antibodies to the macrophage-associated CD68 antigen, also were evaluated for comparison. CD163 immunoreactivity was observed in resident macrophages of all normal tissue samples except splenic white pulp macrophages and germinal center tingible body macrophages. Among hematopoietic disorders and nonhematopoietic neoplasms, CD163 expression was restricted largely to cases of chronic myelomonocytic leukemia, histiocytic sarcoma, sinus histiocytosis with massive lymphadenopathy, and littoral cell angioma. Acute myeloid leukemias (AMLs) with monocytic differentiation were CD163- with the exception of 1 case of acute monoblastic leukemia. Most myeloid sarcomas also were CD163-. Compared with the CD68 antibodies, CD163 demonstrated greater specificity as a marker of disorders of monocyte/macrophage origin. However, immunohistochemical evaluation of CD163 expression does not seem to be a sensitive means of determining monocytic differentiation in AMLs in paraffin sections or establishing a diagnosis of myeloid sarcoma.

Antigens, CD↗
PubMed2003

Histiocytic lesions involving the bone marrow.

Histiocytic lesions involving the bone marrow include a number of reactive and neoplastic disorders. This article discusses the morphologic, immunophenotypic, and genotypic features of a variety of diseases associated with histiocytes and/or monocytes. Lysosomal storage disorders and hemophagocytic syndromes are often first diagnosed by bone marrow examination. Granulomas involving the bone marrow may also be the first indication of a systemic disorder. Apart from acute and chronic monocytic leukemias, the bone marrow is rarely involved by malignant histiocytic disorders, of which Langerhans cell histiocytosis is the most common.

Bone Marrow↗
PubMed2003

Hepatocyte antigen as a marker of intestinal metaplasia.

Intestinal metaplasia is a histologic hallmark of Barrett's esophagus and chronic gastritis. Intestinal metaplasia may progress to dysplasia or carcinomas without proper treatment. Most cases of intestinal metaplasia are easily recognized on hematoxylin and eosin-stained sections. However, some cases of intestinal metaplasia may be hard to recognize if they lack the characteristic mucin-producing cells and Paneth cells, or if they are small in size. Recently, keratin 7, keratin 20, and MUC2 expression patterns were reported to be useful in confirming the diagnosis of intestinal metaplasia. We studied hepatocyte (Hep) antigen (a hepatocellular antigen mainly expressing in normal and neoplastic hepatic tissues) in 33 cases of Barrett's esophagus (9 cases associated with esophageal adenocarcinoma) and 13 cases of chronic gastritis associated with intestinal metaplasia and gastric adenocarcinoma. Hep monoclonal antibody recognizes intestinal metaplasia in all cases. We also compared expression of Hep with that of keratin 7, keratin 20, and MUC2 in intestinal metaplasia. The specificity and sensitivity of Hep for intestinal metaplasia were higher than that of keratin 7 and keratin 20, or MUC2. We conclude that Hep may be used as a single diagnostic marker for intestinal metaplasia.

Adenocarcinoma↗
PubMed2003

Epstein-Barr virus infection is not associated with fibroadenomas of the breast in immunosuppressed patients after organ transplantation.

Epstein-Barr virus has been linked to an increasing number of nonhematolymphoid conditions. Epstein-Barr virus was recently described in association with fibroadenomas of the breast occurring in immunosuppressed patients. To further investigate the potential association of Epstein-Barr virus with fibroadenoma in the context of immune dysfunction, 11 cases of fibroadenoma of the breast in immunosuppressed organ transplant recipients were examined. Cases were evaluated for the presence of Epstein-Barr virus by polymerase chain reaction, in situ hybridization, and immunohistochemical methods. The presence of Epstein-Barr virus genomic DNA was studied by polymerase chain reaction amplification using primers flanking the BamHI-W fragment of the Epstein-Barr virus genome, as well as the Epstein-Barr virus nuclear antigen-4 and latent membrane protein-1 genes. Cases were also evaluated for the presence of defective heterogeneous Epstein-Barr virus DNA. In addition, morphologic analysis by in situ hybridization for Epstein-Barr virus-encoded RNA-1 and immunohistochemistry for latent membrane protein-1 were performed. Epstein-Barr virus DNA was detected in 4 of 11 (36%) cases with BamHI-W polymerase chain reaction. Polymerase chain reaction studies for Epstein-Barr virus nuclear antigen-4 and latent membrane protein-1 genes were positive in two and four cases, respectively. No defective Epstein-Barr virus genomes were identified in any of the cases. Quantitative polymerase chain reaction demonstrated low levels of Epstein-Barr virus in the fibroadenomas studied. Despite the detection of Epstein-Barr virus genomes in a subset of the cases examined, the constituent epithelial and stromal components of all fibroadenomas demonstrated no evidence of Epstein-Barr virus-encoded RNA-1 by in situ hybridization or latent membrane protein-1 expression by immunohistochemistry. Rare Epstein-Barr virus-encoded RNA-1-positive lymphocytes were observed in some cases, which may account for the positive polymerase chain reaction results. The findings of the present study argue against a significant relationship between Epstein-Barr virus and fibroadenomas of the breast in the setting of transplant-associated immunosuppression.

Adolescent↗
PubMed2003

Expression of T/NK-cell and plasma cell antigens in nonhematopoietic epithelioid neoplasms. An immunohistochemical study of 447 cases.

We studied the expression of CD2, CD3, CD4, CD5, CD7, CD8, CD56, and CD138 in 447 cases of common human neoplasms with epithelioid features. CD2, CD3, CD4, and CD8 antigens were detected in none of 447 cases of nonhematopoietic tumors. CD5 and CD7 antigens were expressed in 12.3% and 19.5% of cases of nonhematopoietic tumors, respectively. Their expression was found primarily in adenocarcinomas from the gastrointestinal tract, breast, and female reproductive organs. The high expression of CD5 and CD7 antigen in pancreatic ductal carcinoma and cholangiocarcinoma and high expression of CD7 in epithelioid sarcoma may have diagnostic value. One quarter of cases were positive for CD56. Overexpression of CD56 antigen was detected mainly in neuroendocrine tumors or adenocarcinomas with neuroendocrine differentiation. Its consistent overexpression in adrenal cortical and thyroid tumors may have diagnostic usefulness. Virtually all tumor types studied were CD138+ with a variable positivity rate. The negative staining of CD138 in malignant mesothelioma may be useful for separating mesothelioma from metastatic adenocarcinoma.

Antigens, CD↗
PubMed2002

Diagnostic utility of bilateral bone marrow examination: significance of morphologic and ancillary technique study in malignancy.

BACKGROUND: To retrospectively evaluate the significance of morphologic examination and ancillary studies performed on bilateral bone marrow biopsy specimens, 1864 bone marrow samples were studied. METHODS: Bilateral bone marrow biopsy specimens included 883 specimens that were evaluated for involvement by non-Hodgkin lymphoma (NHL); 381 specimens that were evaluated for involvement by carcinoma (CA); 362 specimens that were evaluated for involvement by Hodgkin disease (HD); 94 specimens that were evaluated for involvement by sarcoma (SA); 56 specimens that were evaluated for involvement by multiple myeloma (MM); 53 specimens that were evaluated for involvement by acute and chronic leukemia, myelodysplasia, and/or myeloproliferative disorders (LEUK); and 35 specimens that were evaluated for other reasons. RESULTS: Of all 1864 specimens, 410 samples (22.0%) were positive for disease, including 77% of MM samples, 58% of LEUK samples, 29.6% of NHL samples, 14% of SA samples, 9.9% of HD samples, and 6.8% of CA samples. A discrepancy between the left and right sides was identified in 48 specimens (11.7% of positive samples). The discrepancy rate was 39% for HD samples, 29% for SA samples, 23% for CA samples, and 9.2% for NHL samples. No morphologic discrepancies between bilateral samples were found in MM samples or LEUK samples. Bilateral flow cytometric studies (n = 113 samples) were positive in 11 samples (9.7%; all morphologically positive), with two discrepancies detected between bilateral samples. Bilateral cytogenetic studies (n = 74 samples) were positive in 5 samples (7%), and there were no discrepancies. Bilateral molecular studies (n = 16 samples) were positive in 7 samples (44%), and there were 3 discrepancies. CONCLUSIONS: Bilateral morphologic evaluation is useful in the evaluation of patients with NHL, HD, CA, and SA and is not indicated for patients with acute or chronic leukemia, myelodysplasia, MM, and other diseases. Bilateral flow cytometric or cytogenetic studies of bone marrow did not provide additional information in this population to justify bilateral samples. The role of bilateral molecular analysis needs to be defined further, but pooled samples for molecular studies may be adequate.

Biopsy↗
PubMed2002

Expression of cytokeratin 5/6 in epithelial neoplasms: an immunohistochemical study of 509 cases.

Cytokeratin 5/6 (CK 5/6) immunoreactivity has been observed in the vast majority of cases of malignant mesothelioma but only rarely in pulmonary adenocarcinomas. Thus, CK 5/6 has been used to distinguish malignant mesothelioma from pulmonary adenocarcinoma. However, the utility of CK 5/6 in distinguishing pleural malignant mesothelioma from pleural metastases from nonpulmonary adenocarcinoma, as well as peritoneal malignant mesothelioma from peritoneal metastatic adenocarcinoma, has not yet been adequately addressed because the tissue expression of CK 5/6 in nonpulmonary neoplasms has not been well defined. We have studied the CK 5/6 expression in 509 cases of various epithelial tumors by immunohistochemistry. We found that the vast majority of cases of squamous cell carcinoma, basal cell carcinoma, thymoma, salivary gland tumor, and biphasic malignant mesothelioma were positive for CK 5/6. In addition, CK 5/6 immunoreactivity was detected in 15 of 24 cases (62%) of transitional cell carcinoma, in 5 of 10 cases (50%) of endometrial adenocarcinoma, in about one third of cases of pancreatic adenocarcinoma (38%) and breast adenocarcinoma (31%), and in one quarter of cases of ovarian adenocarcinomas (25%). Our study confirms the diagnostic utility of CK 5/6 immunohistochemistry in distinguishing biphasic mesothelioma from pulmonary adenocarcinoma but raises caution about its use for the differential diagnosis of pleural or peritoneal malignant mesothelioma versus pleural or peritoneal metastatic nonpulmonary adenocarcinoma, because many types of nonpulmonary adenocarcinomas may be positive for CK 5/6.

Adenocarcinoma↗
PubMed2002

Recurrent B-cell neoplasms after Rituximab therapy: an immunophenotypic and genotypic study.

Rituximab has been widely used to treat relapsing or advanced stage B-cell neoplasms with an efficacy of about 50%. However, approximately 40-50% of Rituximab treated patients will recur. It is not clear whether these recurrent diseases have the same immunophenotype as that of the original tumors. At the City of Hope, we treated 91 cases of CD20-positive B-cell neoplasms with Rituximab in combination with chemotherapy and hematopoietic stem cell transplantation between August 1999 and December 2000. Thirty-five of 91 patients (38%) experienced recurrence during the time period within one year from treatment. Tumor cells from all of the recurrent patients expressed one or more B cell antigens (CD19, CD20, CD22, CD45RA, or CD79a). However, thirteen of 35 recurrent cases showed aberrant loss of CD20 expression (37%) by immunohistochemical or flow cytometric studies. Pre- and post-Rituximab treated tumor cell DNA was successfully extracted from archival paraffin sections, hematoxylin and eosin (H and E) stained slides, smears, or frozen cells in 10 of 13 CD20 negative recurrent cases. PCR studies for immunoglobulin (Ig) heavy chain gene rearrangements were performed in all these cases. Five cases showed identical Ig heavy chain gene rearrangements in the paired specimens. PCR assay for Ig kappa (kappa) gene rearrangement was performed in the five paired specimens lacking detectable Ig heavy chain gene rearrangements; 2 of them showed identical Igkappa gene rearrangements. Three pairs showed unmatched Ig heavy chain and Igkappa gene rearrangements, probably due to poor quality of recovered DNA. Aberrant loss of CD20 antigens may be a mechanism of treatment resistance and should be considered in the immunophenotyping of recurrent Rituximab-treated B-cell neoplasms; therefore, a panel of B cell markers is recommended for the immunologic diagnosis of recurrent B cell malignancies after Rituximab therapy. Seven of ten pairs of recurrent CD20-negative cases showed identical Ig heavy chain and Igkappa gene rearrangements by PCR assay, strongly suggesting that the pre- and post-Rituxan treated B cell neoplasms are clonally-related.

Antibodies, Monoclonal↗
PubMed2002

Long-term survival after radical operations for cancer treatment-induced sarcomas: how two survivors invite reflection on oncologic treatment concepts.

Extent and radicality of surgical oncologic treatment has changed in the past 30 years. Two patients with node-positive breast cancer are presented, who underwent (total or radical) mastectomy with lymphadenectomy and postoperative radiation 24 and 40 years ago. A radiation-associated sarcoma of the parascapular soft tissue developed in one patient 9 years after treatment; the other one sought treatment for a lymphedema-associated Stewart-Treves lymphangiosarcoma 16 years after initial therapy. Both patients underwent a forequarter amputation for their treatment-associated high-grade sarcoma. Both are currently alive and cancer-free 15 and 24 years after amputation. These reports remind us that radical locoregional treatment can cure some solid cancers in the absence of systemic therapy; that such extensive treatment may induce significant disability or secondary malignancies long-term; that even advanced treatment-associated sarcomas can be cured with aggressive resection; that today's multimodality therapy approaches and appropriate patient selection have rendered such extensive locoregional treatment for many tumors obsolete or unnecessary; and that if no effective alternative treatment exists and organ or limb preservation is not feasible, an aggressive resection approach for high-grade cancer should not be discounted unless systemic failure is certain or imminent.

Amputation, Surgical↗
PubMed2002

Hepatocyte antigen as a marker of hepatocellular carcinoma: an immunohistochemical comparison to carcinoembryonic antigen, CD10, and alpha-fetoprotein.

Hepatocyte monoclonal antibody (Hep) (alternatively Hep Par 1 for Hep paraffin 1) has been reported to stain normal hepatic tissue and hepatocellular carcinoma (HCC) with high specificity. We have studied the Hepatocyte expression in 96 cases of HCC and 311 cases of nonhepatic epithelial tumors. All cases of HCC were also stained with CEA-Gold 5, CD10, and alpha-fetoprotein. Hep, CEA-Gold 5, CD10, and alpha-fetoprotein immunostains were performed on formalin-fixed, paraffin-embedded tissue sections. Hep immunoreactivity was detected in 88 of 96 cases of HCC (92%), with a cytoplasmic and granular pattern of staining. The level of Hep expression in HCC corresponded to the nuclear grade and growth pattern. All 50 cases of nuclear grade 1 and nuclear grade 2 HCC were positive (100%), whereas 37 of 44 nuclear grade 3 (84%) and 1 of 2 nuclear grade 4 (50%) were positive. Sixty-seven of 68 cases of HCC with a trabecular, pseudoglandular, or scirrhous growth pattern were positive (98%), whereas 22 of 27 cases of HCC with a compact growth pattern were positive (81%). CEA-Gold 5, CD10, and alpha-fetoprotein immunoreactivity was detected in 76% (73 of 96), 52% (50 of 96), and 31% (30 of 96) cases of HCC, respectively. The positive predictive value of the combination of all four antibodies was 97%. Three cases of HCC were negative for all four antibodies; these cases had a high nuclear grade or a sarcomatoid or compact growth pattern. Twenty of 311 cases of nonhepatic tumors were positive for Hep (6%): 15 were adenocarcinomas and five were neuroendocrine tumors. The negative predictive value of Hep in HCC was 94%. The Hep-positive nonhepatic epithelial tumors were easily distinguished from HCC by the expression of keratin 7 or keratin 20 for adenocarcinoma and chromogranin and synaptophysin for neuroendocrine tumors because HCC does usually not express these markers. With the exception of two cases of hepatoid gastric carcinoma, all Hep-positive nonhepatic epithelial tumors were negative for alpha-fetoprotein, CEA-Gold 5, and CD10. Our study demonstrates that Hep is a relatively specific marker for HCC. It is useful in differentiating HCC from primary hepatic cholangiocarcinoma and metastatic tumors when combined with other immunomarkers.

Antibodies, Monoclonal↗
PubMed2002

Epstein-Barr virus nuclear antigen (EBNA)-1 carboxy-terminal and EBNA-4 sequence polymorphisms in nasal natural killer/T-cell lymphoma in the United States.

Epstein-Barr virus (EBV) polymorphisms were examined in 12 cases of nasal natural killer (NK)/T-cell lymphoma diagnosed in the United States (U.S.-NL) with respect to the EBV-associated nuclear antigen (EBNA)-1 carboxy (C)-terminal region and the EBNA-4 region. A single dominant EBV strain was found in all cases. EBNA-1 sequences were remarkably homogeneous, showing either a P-ala (2/12) or P-ala variant (9/12) sequence. Other EBNA-1 subtypes known to be common in U.S.-reactive samples, such as P-thr or V-leu, were not identified. The final case had a base deletion with frame shift and premature stop codon. EBNA-1 C-terminal amino acid substitutions were common at codons 499 (10/12 cases), 502 (7/12), 524 (9/12), and 528 (6/12), all previously reported "hot spots." However, unlike previous reports of other EBV-associated neoplastic and reactive tissues, mutations were absent at residues 487 and 492. Mutations within HLA-A11-restricted immunogenic EBNA-4 epitopes 399-408 and 416-424 occurred in 3 of 12 cases but were not associated with HLA-A11 status. In summary, the exclusive finding of P-ala variant or P-ala EBNA-1 sequences in U.S.-NL cases differs from that reported in U.S.-reactive and non-U.S.-NL cases. Although the significance of this difference is not known for certain, it may be related to geographic and/or site-specific variations, rather than oncogenicity per se.

Amino Acid Sequence↗