- Email: [email protected]
HIV infection and c-MYC status in endemic Burkitt lymphoma
1408
Correspondence
mutations in the E-cadherin gene, the implication of this being that the aberrant E-cadherin protein expression is not related to abnormalities of the gene. We have also examined the role of p120, a molecule that is thought to be a regulator of E-cadherin [9]. All 29 cases in that series showed aberrant localization of p120, thus suggesting that p120 may be the effector of E-cadherin abnormalities in SPT. E-cadherin immunoexpression abnormalities are seen in 100% of cases of SPT of the pancreas. These may be of 2 forms depending on the antibody used: complete absence of staining or nuclear immunolabeling. It should be remembered that nuclear E-cadherin is also seen in pancreatic neuroendocrine tumors; pancreatic ductal adenocarcinomas; and renal cell, esophageal squamous, and colorectal cancers. As awareness regarding nuclear localization of E-cadherin increases, more cancers with this staining pattern will emerge. Although the exact mechanism(s) for nuclear translocation of E-cadherin is not well elucidated at this juncture, it is clear that it is the cytoplasmic domain of the molecule that has a nuclear locale. It is also quite likely that p120 abnormalities are pivotal in the causation of E-cadherin abnormalities. Runjan Chetty MB, BCh, FRCPath, FRCPC, DPhil Stefano Serra MD Department of Pathology University Health Network/University of Toronto Toronto, Canada MG5 2C4 E-mail address: [email protected] Sima Salahshor PhD Samuel Lunenfeld Research Institute Mount Sinai Hospital, Toronto, Canada MG5 2C4 doi:10.1016/j.humpath.2008.05.015
References [1] Kim M-J, Jang S-J, Yu E. Loss of E-cadherin and cytoplasmic-nuclear expression of b-catenin are the most useful immunoprofiles in the diagnosis of solid-pseudopapillary neoplasm of the pancreas. HUM PATHOL 2008;39:251-8. [2] Serra S, Salahshor S, Fagih M, et al. Nuclear expression of E-cadherin in solid pseudopapillary tumors of the pancreas. J Pancreas 2007;8: 296-303. [3] Tang WT, Stelter AA, French S, et al. Loss of cell-adhesion molecule complexes in solid pseudopapillary tumor of the pancreas. Mod Pathol 2007;20:509-13. [4] Chetty R, Serra S. Membrane loss and aberrant nuclear localization of E-cadherin are consistent features of solid pseudopapillary tumour of the pancreas. An immunohistochemical study using two antibodies recognizing different domains of the E-cadherin molecule. Histopathology 2008;52:325-30. [5] Chetty R, Serra S, Asa SL. Loss of membrane localization and aberrant nuclear E-cadherin expression correlates with invasion in pancreatic endocrine tumors. Am J Surg Pathol 2008;32:413-9. [6] Salahshor S, Naidoo R, Serra S, et al. Frequent accumulation of nuclear E-cadherin and alterations in the wnt signaling pathway in esophageal squamous carcinomas. Mod Pathol 2008;21:271-81.
[7] Gervais ML, Henry PC, Saravanan A, et al. Nuclear E-cadherin and VHL immunoreactivity are prognostic indicators of clear-cell renal cell carcinoma. Lab Invest 2007;87:1252-64. [8] El-Bahrawy MA, Rowan A, Horncastle D, et al. E-cadherin/catenin complex status in solid pseudopapillary tumor of the pancreas. Am J Surg Pathol 2008;32:1-7. [9] Chetty R, Jain D, Serra S. p120 catenin (p120) reduction and cytoplasmic relocalization leads to dysregulation of E-cadherin in solid pseudopapillary tumors of the pancreas. Am J Clin Pathol 2008;130:71-6.
HIV infection and c-MYC status in endemic Burkitt lymphoma To the Editor: After the acceptance of the paper on B-cell non-Hodgkin lymphomas in Uganda that has recently appeared on line [1], we have further explored the pathobiologic features of Burkitt lymphoma, which had remained unsettled in the course of our previous study. In particular, the prevalence of t(8;14) could not have been assessed due to DNA degradation that hampered the application of probes spanning several hundred base pairs (bp). Recently, Rodig et al [2] reported that the determination of TCL1, CD38, and CD44 can surrogate the molecular investigation. Therefore, we tested the tissue micro-arrays in our hands, corresponding to 95 Ugandan Burkitt lymphomas, by immunohistochemistry and specific antibodies to these molecules to see the frequency of the specific phenotypic algorithms. We found that out of 85 evaluable cases, 73 displayed an antigen combination consistent with the presence of t(8;14). In fact, 64 cases showed positivity for TCL1 and CD38 and negativity for CD44 (Fig. 1), whereas 9 stained for CD38 only. The remaining 12 tumors turned out to be TCL1+, CD38− and CD44− or negative for all markers. The fact that we could not detect hints of the characteristic translocation in all cases may be due to either the lack of a complete correspondence between the immunohistochemical test and FISH/cytogenetics studies or the absence of t(8;14) in about 10% of African Burkitt lymphomas. The latter fact has been recently proposed by Leoncini et al [3] at the International Conference held in Kampala to celebrate the 50th anniversary of the discovery of Burkitt lymphoma. Based on this, we think that for the future, a more controlled sample management should be applied to African lymphoma cases that allow the usage of FISH or tissue cryopreservation. In addition, the detection of both morphologic and phenotypic features of plasmacytoid differentiation in more than 40% of cases had prompted us to question whether or not they might be related to HIV infection, such findings being usually observed in AIDS patients in Western Countries [4]. With this in mind, we extracted the DNA from paraffin blocks and looked for HIV integration by RT-PCR and nested PCR [5] after the evaluation of the adequate preservation of the PLZF gene (300 bp). The
Correspondence
1409 On the one hand, such observation strengthens the concept that plasmacytoid features can reflect the natural history of Burkitt lymphoma consisting of multiple pathogenetic events all stressing the immune system [1], on the other does confirm previous reported figures concerning the very low incidence of HIV infection in African children. Parkin et al [7] found that there is no relationship between HIV infection and the development of Burkitt lymphoma in such population. In fact, children infected by vertical transmission die of AIDS during the first months of life before the factors involved in Burkitt lymphoma pathogenesis (Epstein-Barr Virus, malaria, Arboviruses, and Euphorbia Tirucalli) can play their promotional role.
Cristina Campidelli MD Anna Gazzola BT Francesca Vitone BS Stefano A. Pileri MD Department of Haematology and Oncological Sciences “L. & A. Seragnoli”, Haematopathology and Microbiology Sections, Bologna University School of Medicine St. Orsola Hospital, 40138 Bologna, Italy E-mail address: [email protected] Lynnette Tumwine MD Department of Pathology Makerere University Medical School P.O. Box 7072, Kampala, Uganda doi:10.1016/j.humpath.2008.06.002
References
Fig. 1 The neoplastic cells express TCL1 both at the cytoplasmic and nuclear level (A); scattered normal T-lymphocytes represent the internal negative control. In the same case, positivity and negativity of lymphomatous elements at the determination of CD38 (B) and CD44 (C), respectively (immunoalkaline phosphatase technique, Gill's hematoxylin counterstaining ×40).
probes used for these analyses explored the gag and env regions, spanning 142 and 248 bp, respectively [6]. Notably, none of 95 cases tested showed HIV integration.
[1] Tumwine LK, Campidelli C, Righi S, et al. B-cell non-Hodgkin lymphomas in Uganda: an immunohistochemical appraisal on tissue micro-array. HUM PATHOL 2008;39:817-23. [2] Rodig SJ, Vergilio J, Shahsafaei A, Dorfman D. Characteristic expression patterns of TCL1, CD38, and CD44 identify aggressive lymphomas harboring a MYC translocation. Am J Surg Pathol 2008;32:113-22. [3] Leoncini L, Leucci E, Cocco M, et al. c-MYC negative classical Burkitt lymphoma: alternative pathogenetic mechanism. 50th Anniversary of the discovery of Burkitt Lymphoma. International Conference on Burkitt Lymphoma and Related Lymphoproliferative Disorders, February 25-27, Kampala (Uganda); 2008. [4] Jaffe E, Harris NL, Stein H, Vardiman JW. World Health Organization Classification of tumors. Pathology and genetics of tumors of the Haemopoietic and Lymphoid tissues. Lyon IARC Press; 2001. [5] An SF, Ciardi A, Scaravilli F. PCR detection of HIV proviral DNA (gag) in the brains of patients with AIDS: comparison between results using fresh frozen and paraffin wax embedded specimens. J Clin Pathol 1994;47:990-4. [6] Locateli D, Stoco PH, Zanetti CR, et al. An optimized nested polymerase chain reaction (PCR) approach allows detection and characterization of human immunodeficiency virus type 1 (HIV-1) env and gag genes from clinical samples. J Clin Lab Anal 2008;22:106-13. [7] Parkin DM, Garcia-Giannoli H, Raphael M, et al. Non-Hodgkin lymphoma in Uganda: a case-control study. AIDS 2000;14:2929-36.
Correspondence
mutations in the E-cadherin gene, the implication of this being that the aberrant E-cadherin protein expression is not related to abnormalities of the gene. We have also examined the role of p120, a molecule that is thought to be a regulator of E-cadherin [9]. All 29 cases in that series showed aberrant localization of p120, thus suggesting that p120 may be the effector of E-cadherin abnormalities in SPT. E-cadherin immunoexpression abnormalities are seen in 100% of cases of SPT of the pancreas. These may be of 2 forms depending on the antibody used: complete absence of staining or nuclear immunolabeling. It should be remembered that nuclear E-cadherin is also seen in pancreatic neuroendocrine tumors; pancreatic ductal adenocarcinomas; and renal cell, esophageal squamous, and colorectal cancers. As awareness regarding nuclear localization of E-cadherin increases, more cancers with this staining pattern will emerge. Although the exact mechanism(s) for nuclear translocation of E-cadherin is not well elucidated at this juncture, it is clear that it is the cytoplasmic domain of the molecule that has a nuclear locale. It is also quite likely that p120 abnormalities are pivotal in the causation of E-cadherin abnormalities. Runjan Chetty MB, BCh, FRCPath, FRCPC, DPhil Stefano Serra MD Department of Pathology University Health Network/University of Toronto Toronto, Canada MG5 2C4 E-mail address: [email protected] Sima Salahshor PhD Samuel Lunenfeld Research Institute Mount Sinai Hospital, Toronto, Canada MG5 2C4 doi:10.1016/j.humpath.2008.05.015
References [1] Kim M-J, Jang S-J, Yu E. Loss of E-cadherin and cytoplasmic-nuclear expression of b-catenin are the most useful immunoprofiles in the diagnosis of solid-pseudopapillary neoplasm of the pancreas. HUM PATHOL 2008;39:251-8. [2] Serra S, Salahshor S, Fagih M, et al. Nuclear expression of E-cadherin in solid pseudopapillary tumors of the pancreas. J Pancreas 2007;8: 296-303. [3] Tang WT, Stelter AA, French S, et al. Loss of cell-adhesion molecule complexes in solid pseudopapillary tumor of the pancreas. Mod Pathol 2007;20:509-13. [4] Chetty R, Serra S. Membrane loss and aberrant nuclear localization of E-cadherin are consistent features of solid pseudopapillary tumour of the pancreas. An immunohistochemical study using two antibodies recognizing different domains of the E-cadherin molecule. Histopathology 2008;52:325-30. [5] Chetty R, Serra S, Asa SL. Loss of membrane localization and aberrant nuclear E-cadherin expression correlates with invasion in pancreatic endocrine tumors. Am J Surg Pathol 2008;32:413-9. [6] Salahshor S, Naidoo R, Serra S, et al. Frequent accumulation of nuclear E-cadherin and alterations in the wnt signaling pathway in esophageal squamous carcinomas. Mod Pathol 2008;21:271-81.
[7] Gervais ML, Henry PC, Saravanan A, et al. Nuclear E-cadherin and VHL immunoreactivity are prognostic indicators of clear-cell renal cell carcinoma. Lab Invest 2007;87:1252-64. [8] El-Bahrawy MA, Rowan A, Horncastle D, et al. E-cadherin/catenin complex status in solid pseudopapillary tumor of the pancreas. Am J Surg Pathol 2008;32:1-7. [9] Chetty R, Jain D, Serra S. p120 catenin (p120) reduction and cytoplasmic relocalization leads to dysregulation of E-cadherin in solid pseudopapillary tumors of the pancreas. Am J Clin Pathol 2008;130:71-6.
HIV infection and c-MYC status in endemic Burkitt lymphoma To the Editor: After the acceptance of the paper on B-cell non-Hodgkin lymphomas in Uganda that has recently appeared on line [1], we have further explored the pathobiologic features of Burkitt lymphoma, which had remained unsettled in the course of our previous study. In particular, the prevalence of t(8;14) could not have been assessed due to DNA degradation that hampered the application of probes spanning several hundred base pairs (bp). Recently, Rodig et al [2] reported that the determination of TCL1, CD38, and CD44 can surrogate the molecular investigation. Therefore, we tested the tissue micro-arrays in our hands, corresponding to 95 Ugandan Burkitt lymphomas, by immunohistochemistry and specific antibodies to these molecules to see the frequency of the specific phenotypic algorithms. We found that out of 85 evaluable cases, 73 displayed an antigen combination consistent with the presence of t(8;14). In fact, 64 cases showed positivity for TCL1 and CD38 and negativity for CD44 (Fig. 1), whereas 9 stained for CD38 only. The remaining 12 tumors turned out to be TCL1+, CD38− and CD44− or negative for all markers. The fact that we could not detect hints of the characteristic translocation in all cases may be due to either the lack of a complete correspondence between the immunohistochemical test and FISH/cytogenetics studies or the absence of t(8;14) in about 10% of African Burkitt lymphomas. The latter fact has been recently proposed by Leoncini et al [3] at the International Conference held in Kampala to celebrate the 50th anniversary of the discovery of Burkitt lymphoma. Based on this, we think that for the future, a more controlled sample management should be applied to African lymphoma cases that allow the usage of FISH or tissue cryopreservation. In addition, the detection of both morphologic and phenotypic features of plasmacytoid differentiation in more than 40% of cases had prompted us to question whether or not they might be related to HIV infection, such findings being usually observed in AIDS patients in Western Countries [4]. With this in mind, we extracted the DNA from paraffin blocks and looked for HIV integration by RT-PCR and nested PCR [5] after the evaluation of the adequate preservation of the PLZF gene (300 bp). The
Correspondence
1409 On the one hand, such observation strengthens the concept that plasmacytoid features can reflect the natural history of Burkitt lymphoma consisting of multiple pathogenetic events all stressing the immune system [1], on the other does confirm previous reported figures concerning the very low incidence of HIV infection in African children. Parkin et al [7] found that there is no relationship between HIV infection and the development of Burkitt lymphoma in such population. In fact, children infected by vertical transmission die of AIDS during the first months of life before the factors involved in Burkitt lymphoma pathogenesis (Epstein-Barr Virus, malaria, Arboviruses, and Euphorbia Tirucalli) can play their promotional role.
Cristina Campidelli MD Anna Gazzola BT Francesca Vitone BS Stefano A. Pileri MD Department of Haematology and Oncological Sciences “L. & A. Seragnoli”, Haematopathology and Microbiology Sections, Bologna University School of Medicine St. Orsola Hospital, 40138 Bologna, Italy E-mail address: [email protected] Lynnette Tumwine MD Department of Pathology Makerere University Medical School P.O. Box 7072, Kampala, Uganda doi:10.1016/j.humpath.2008.06.002
References
Fig. 1 The neoplastic cells express TCL1 both at the cytoplasmic and nuclear level (A); scattered normal T-lymphocytes represent the internal negative control. In the same case, positivity and negativity of lymphomatous elements at the determination of CD38 (B) and CD44 (C), respectively (immunoalkaline phosphatase technique, Gill's hematoxylin counterstaining ×40).
probes used for these analyses explored the gag and env regions, spanning 142 and 248 bp, respectively [6]. Notably, none of 95 cases tested showed HIV integration.
[1] Tumwine LK, Campidelli C, Righi S, et al. B-cell non-Hodgkin lymphomas in Uganda: an immunohistochemical appraisal on tissue micro-array. HUM PATHOL 2008;39:817-23. [2] Rodig SJ, Vergilio J, Shahsafaei A, Dorfman D. Characteristic expression patterns of TCL1, CD38, and CD44 identify aggressive lymphomas harboring a MYC translocation. Am J Surg Pathol 2008;32:113-22. [3] Leoncini L, Leucci E, Cocco M, et al. c-MYC negative classical Burkitt lymphoma: alternative pathogenetic mechanism. 50th Anniversary of the discovery of Burkitt Lymphoma. International Conference on Burkitt Lymphoma and Related Lymphoproliferative Disorders, February 25-27, Kampala (Uganda); 2008. [4] Jaffe E, Harris NL, Stein H, Vardiman JW. World Health Organization Classification of tumors. Pathology and genetics of tumors of the Haemopoietic and Lymphoid tissues. Lyon IARC Press; 2001. [5] An SF, Ciardi A, Scaravilli F. PCR detection of HIV proviral DNA (gag) in the brains of patients with AIDS: comparison between results using fresh frozen and paraffin wax embedded specimens. J Clin Pathol 1994;47:990-4. [6] Locateli D, Stoco PH, Zanetti CR, et al. An optimized nested polymerase chain reaction (PCR) approach allows detection and characterization of human immunodeficiency virus type 1 (HIV-1) env and gag genes from clinical samples. J Clin Lab Anal 2008;22:106-13. [7] Parkin DM, Garcia-Giannoli H, Raphael M, et al. Non-Hodgkin lymphoma in Uganda: a case-control study. AIDS 2000;14:2929-36.