TY - JOUR
T1 - Sonic hedgehog signaling proteins and ATP-binding cassette G2 are aberrantly expressed in diffuse large B-Cell lymphoma
AU - Kim, Ji Eun
AU - Singh, Rajesh R.
AU - Cho-Vega, Jeong Hee
AU - Drakos, Elias
AU - Davuluri, Yogesh
AU - Khokhar, Faisal A.
AU - Fayad, Luis
AU - Medeiros, L. Jeffrey
AU - Vega, Francisco
N1 - Funding Information:
Correspondence: Dr F Vega, MD, PhD, Department of Hematopathology, Unit 72, The University of Texas MD Anderson Cancer Center, Box 72, 1515 Holcombe BLVD, Houston, TX 77030, USA. E-mail: fvegava@mdanderson.org This paper was presented in part at the United States and Canadian Academy of Pathology (USCAP) Annual meeting, Boston, MA, 7–13 March 2009. *Dr JE Kim did this work as a visiting scientist supported by the Department of Pathology, Seoul National University, Boramae Hospital, Seoul, Korea. Received 28 March 2009; revised 28 May 2009; accepted 29 May 2009; published online 10 July 2009
Funding Information:
This research was supported by funds from the University Cancer Foundation at The University of Texas MD Anderson Cancer Center.
PY - 2009/10
Y1 - 2009/10
N2 - Dysregulation of the sonic hedgehog (SHH) signaling pathway has been shown in several cancer types, but has not been explored in diffuse large B-cell lymphoma. We assessed 67 cases of diffuse large B-cell lymphoma for expression of SHH (ligand), GLI1, GLI2 and GLI3 (transcriptional effectors of SHH signaling), and the ATP-binding cassette (ABC)G2 (a downstream target of SHH signaling), using immunohistochemistry. For comparison, we assessed the expression levels of these proteins in 28 cases of follicular lymphoma, 5 chronic lymphocytic leukemia/small lymphocytic lymphoma, and 5 reactive lymph nodes. In diffuse large B-cell lymphoma, SHH was expressed in 61 of 67 (91%) cases, GLI1 in 62 of 67 (93%), GLI2 in 41 of 56 (73%), and GLI3 in 22 of 56 (39%). Expression of ABCG2 was detected in 52 of 55 (95%) cases and was high in 15 (27%) cases. SHH expression positively correlated with expression levels of ABCG2 (P0.05). Patients with diffuse large B-cell lymphoma with high ABCG2 expression showed significantly shorter overall survival (P0.031) and failure-free survival (P0.029) compared with patients with tumors with low or no expression of ABCG2. Diffuse large B-cell lymphomas expressed SHH, and GLI1, GLI2, and GLI3 more frequently and more intensely than cases of follicular lymphoma or chronic lymphocytic leukemia/small lymphocytic lymphoma. In conclusion, our data show that SHH signaling proteins and ABCG2 are aberrantly expressed in diffuse large B-cell lymphoma and that ABCG2 expression has prognostic implications. These findings also provide evidence that dysregulation of the SHH pathway may be involved in the pathogenesis of diffuse large B-cell lymphoma.
AB - Dysregulation of the sonic hedgehog (SHH) signaling pathway has been shown in several cancer types, but has not been explored in diffuse large B-cell lymphoma. We assessed 67 cases of diffuse large B-cell lymphoma for expression of SHH (ligand), GLI1, GLI2 and GLI3 (transcriptional effectors of SHH signaling), and the ATP-binding cassette (ABC)G2 (a downstream target of SHH signaling), using immunohistochemistry. For comparison, we assessed the expression levels of these proteins in 28 cases of follicular lymphoma, 5 chronic lymphocytic leukemia/small lymphocytic lymphoma, and 5 reactive lymph nodes. In diffuse large B-cell lymphoma, SHH was expressed in 61 of 67 (91%) cases, GLI1 in 62 of 67 (93%), GLI2 in 41 of 56 (73%), and GLI3 in 22 of 56 (39%). Expression of ABCG2 was detected in 52 of 55 (95%) cases and was high in 15 (27%) cases. SHH expression positively correlated with expression levels of ABCG2 (P0.05). Patients with diffuse large B-cell lymphoma with high ABCG2 expression showed significantly shorter overall survival (P0.031) and failure-free survival (P0.029) compared with patients with tumors with low or no expression of ABCG2. Diffuse large B-cell lymphomas expressed SHH, and GLI1, GLI2, and GLI3 more frequently and more intensely than cases of follicular lymphoma or chronic lymphocytic leukemia/small lymphocytic lymphoma. In conclusion, our data show that SHH signaling proteins and ABCG2 are aberrantly expressed in diffuse large B-cell lymphoma and that ABCG2 expression has prognostic implications. These findings also provide evidence that dysregulation of the SHH pathway may be involved in the pathogenesis of diffuse large B-cell lymphoma.
KW - ABCG2
KW - GLI; diffuse large B-cell lymphoma
KW - Sonic hedgehog (SHH) signaling pathway
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U2 - 10.1038/modpathol.2009.98
DO - 10.1038/modpathol.2009.98
M3 - Article
C2 - 19593328
AN - SCOPUS:70349694160
SN - 0893-3952
VL - 22
SP - 1312
EP - 1320
JO - Modern Pathology
JF - Modern Pathology
IS - 10
ER -