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Published in: Annals of Surgical Oncology 9/2009

01-09-2009 | Hepatobiliary and Pancreatic Tumors

CD74 Is a Novel Prognostic Factor for Patients with Pancreatic Cancer Receiving Multimodal Therapy

Authors: Shigenori Nagata, MD, PhD, Yu-Fen Jin, MD, PhD, Katsuhiko Yoshizato, Miki Tomoeda, DDS, PhD, Misa Song, MD, Norishige Iizuka, MD, Masanori Kitamura, MD, Hidenori Takahashi, MD, PhD, Hidetoshi Eguchi, MD, PhD, Hiroaki Ohigashi, MD, PhD, Osamu Ishikawa, MD, PhD, Yasuhiko Tomita, MD, PhD

Published in: Annals of Surgical Oncology | Issue 9/2009

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Abstract

Background

Pancreatic ductal adenocarcinoma (PDAC) is still one of the most fatal cancers, although its prognosis has improved recently with the introduction of multimodal therapy. To further develop effective treatment for PDAC, establishment of prognostic indicators for patients receiving multimodal therapy is essential.

Methods

Sixty-eight patients receiving curative extended resection combined with preoperative chemoradiation and postoperative chemotherapy for primary PDAC were selected. Immunohistochemistry using anti-CD74 antibody on paraffin-embedded tissue samples was performed, and cases were divided into two groups according to the ratio of CD74-positive cells: expression level I, CD74-positive cells <70%; level II, CD74-positive cells ≥70%. The correlation of CD74 expression level with clinicopathological features and overall survival was evaluated.

Results

Forty-seven (69.1%) and 21 (30.9%) patients showed level I and II CD74 expression, respectively. Patients with level II CD74 expression showed a higher rate of lymphatic permeation (P = 0.04) and perineural invasion (P = 0.01) compared with those with level I expression. Patients with level I CD74 expression had a significantly better survival rate than those with level II (P = 0.003). Among the patients with pathological tumor–node–metastasis stages I and II, those with level I CD74 expression showed a significantly better prognosis than those with level II (P = 0.006). Multivariate analysis revealed CD74 expression level and vascular permeation of carcinoma as independent prognostic indicators.

Conclusions

CD74 expression proved as a useful prognostic indicator for PDAC treated with multimodal therapy.
Literature
1.
go back to reference Niederhuber JE, Brennan MF, Menck HR. The National Cancer Data Base report on pancreatic cancer. Cancer. 1995;76:1671–7.PubMedCrossRef Niederhuber JE, Brennan MF, Menck HR. The National Cancer Data Base report on pancreatic cancer. Cancer. 1995;76:1671–7.PubMedCrossRef
2.
go back to reference Conlon KC, Klimstra DS, Brennan MF. Long-term survival after curative resection for pancreatic ductal adenocarcinoma. Clinicopathologic analysis of 5-year survivors. Ann Surg. 1996;223:273–9.PubMedCrossRef Conlon KC, Klimstra DS, Brennan MF. Long-term survival after curative resection for pancreatic ductal adenocarcinoma. Clinicopathologic analysis of 5-year survivors. Ann Surg. 1996;223:273–9.PubMedCrossRef
3.
go back to reference Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ. Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71–96.PubMedCrossRef Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ. Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71–96.PubMedCrossRef
4.
go back to reference Gebhardt C, Meyer W, Reichel M, Wunsch PH. Prognostic factors in the operative treatment of ductal pancreatic carcinoma. Langenbecks Arch Surg. 2000;385:14–20.PubMedCrossRef Gebhardt C, Meyer W, Reichel M, Wunsch PH. Prognostic factors in the operative treatment of ductal pancreatic carcinoma. Langenbecks Arch Surg. 2000;385:14–20.PubMedCrossRef
5.
go back to reference Breslin TM, Hess KR, Harbison DB, et al. Neoadjuvant chemoradiotherapy for adenocarcinoma of the pancreas: treatment variables and survival duration. Ann Surg Oncol. 2001;8:123–32.PubMedCrossRef Breslin TM, Hess KR, Harbison DB, et al. Neoadjuvant chemoradiotherapy for adenocarcinoma of the pancreas: treatment variables and survival duration. Ann Surg Oncol. 2001;8:123–32.PubMedCrossRef
6.
go back to reference Brunner TB, Grabenbauer GG, Meyer T, Golcher H, Sauer R, Hohenberger W. Primary resection versus neoadjuvant chemoradiation followed by resection for locally resectable or potentially resectable pancreatic carcinoma without distant metastasis. A multi-centre prospectively randomized phase II-study of the Interdisciplinary Working Group Gastrointestinal Tumours (AIO, ARO, and CAO). BMC Cancer. 2007;7:41.PubMedCrossRef Brunner TB, Grabenbauer GG, Meyer T, Golcher H, Sauer R, Hohenberger W. Primary resection versus neoadjuvant chemoradiation followed by resection for locally resectable or potentially resectable pancreatic carcinoma without distant metastasis. A multi-centre prospectively randomized phase II-study of the Interdisciplinary Working Group Gastrointestinal Tumours (AIO, ARO, and CAO). BMC Cancer. 2007;7:41.PubMedCrossRef
7.
go back to reference Evans DB, Varadhachary GR, Crane CH, et al. Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head. J Clin Oncol. 2008;26:3496–502.PubMedCrossRef Evans DB, Varadhachary GR, Crane CH, et al. Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head. J Clin Oncol. 2008;26:3496–502.PubMedCrossRef
8.
go back to reference Ohigashi H, Ishikawa O, Eguchi H, et al. Feasibility and efficacy of combination therapy with preoperative and postoperative chemoradiation, extended pancreatectomy, and postoperative liver perfusion chemotherapy for locally advanced cancers of the pancreatic head. Ann Surg Oncol. 2005;12:629–36.PubMedCrossRef Ohigashi H, Ishikawa O, Eguchi H, et al. Feasibility and efficacy of combination therapy with preoperative and postoperative chemoradiation, extended pancreatectomy, and postoperative liver perfusion chemotherapy for locally advanced cancers of the pancreatic head. Ann Surg Oncol. 2005;12:629–36.PubMedCrossRef
9.
go back to reference Ishikawa O, Ohigashi H, Sasaki Y, Masao K, Kabuto T, Furukawa H, Imaoka S. Adjuvant therapies in extended pancreatectomy for ductal adenocarcinoma of the pancreas. Hepatogastroenterology. 1998;45:644–50.PubMed Ishikawa O, Ohigashi H, Sasaki Y, Masao K, Kabuto T, Furukawa H, Imaoka S. Adjuvant therapies in extended pancreatectomy for ductal adenocarcinoma of the pancreas. Hepatogastroenterology. 1998;45:644–50.PubMed
10.
go back to reference Uyama H, Tomita Y, Nakamura H, et al. Hepatoma-derived growth factor is a novel prognostic factor for patients with pancreatic cancer. Clin Cancer Res. 2006;12:6043–8.PubMedCrossRef Uyama H, Tomita Y, Nakamura H, et al. Hepatoma-derived growth factor is a novel prognostic factor for patients with pancreatic cancer. Clin Cancer Res. 2006;12:6043–8.PubMedCrossRef
11.
go back to reference Ioachim HL, Pambuccian SE, Hekimgil M, Giancotti FR, Dorsett BH. Lymphoid monoclonal antibodies reactive with lung tumors. Diagnostic applications. Am J Surg Pathol. 1996;20:64–71.PubMedCrossRef Ioachim HL, Pambuccian SE, Hekimgil M, Giancotti FR, Dorsett BH. Lymphoid monoclonal antibodies reactive with lung tumors. Diagnostic applications. Am J Surg Pathol. 1996;20:64–71.PubMedCrossRef
12.
go back to reference Lazova R, Moynes R, May D, Scott G. LN-2 (CD74). A marker to distinguish atypical fibroxanthoma from malignant fibrous histiocytoma. Cancer 1997;79:2115–24.PubMedCrossRef Lazova R, Moynes R, May D, Scott G. LN-2 (CD74). A marker to distinguish atypical fibroxanthoma from malignant fibrous histiocytoma. Cancer 1997;79:2115–24.PubMedCrossRef
13.
go back to reference Young AN, Amin MB, Moreno CS, et al. Expression profiling of renal epithelial neoplasms: a method for tumor classification and discovery of diagnostic molecular markers. Am J Pathol. 2001;158:1639–51.PubMed Young AN, Amin MB, Moreno CS, et al. Expression profiling of renal epithelial neoplasms: a method for tumor classification and discovery of diagnostic molecular markers. Am J Pathol. 2001;158:1639–51.PubMed
14.
go back to reference Hippo Y, Yashiro M, Ishii M, et al. Differential gene expression profiles of scirrhous gastric cancer cells with high metastatic potential to peritoneum or lymph nodes. Cancer Res. 2001;61:889–95.PubMed Hippo Y, Yashiro M, Ishii M, et al. Differential gene expression profiles of scirrhous gastric cancer cells with high metastatic potential to peritoneum or lymph nodes. Cancer Res. 2001;61:889–95.PubMed
15.
go back to reference Jiang Z, Xu M, Savas L, LeClair P, Banner BF. Invariant chain expression in colon neoplasms. Virchows Arch. 1999;435:32–6.PubMedCrossRef Jiang Z, Xu M, Savas L, LeClair P, Banner BF. Invariant chain expression in colon neoplasms. Virchows Arch. 1999;435:32–6.PubMedCrossRef
16.
go back to reference Hustinx SR, Cao D, Maitra A, et al. Differentially expressed genes in pancreatic ductal adenocarcinomas identified through serial analysis of gene expression. Cancer Biol Ther. 2004;3:1254–61.PubMedCrossRef Hustinx SR, Cao D, Maitra A, et al. Differentially expressed genes in pancreatic ductal adenocarcinomas identified through serial analysis of gene expression. Cancer Biol Ther. 2004;3:1254–61.PubMedCrossRef
17.
go back to reference Koide N, Yamada T, Shibata R, et al. Establishment of perineural invasion models and analysis of gene expression revealed an invariant chain (CD74) as a possible molecule involved in perineural invasion in pancreatic cancer. Clin Cancer Res. 2006;12:2419–26.PubMedCrossRef Koide N, Yamada T, Shibata R, et al. Establishment of perineural invasion models and analysis of gene expression revealed an invariant chain (CD74) as a possible molecule involved in perineural invasion in pancreatic cancer. Clin Cancer Res. 2006;12:2419–26.PubMedCrossRef
18.
go back to reference Castells A, Puig P, Mora J, et al. K-ras mutations in DNA extracted from the plasma of patients with pancreatic carcinoma: diagnostic utility and prognostic significance. J Clin Oncol. 1999;17:578–84.PubMed Castells A, Puig P, Mora J, et al. K-ras mutations in DNA extracted from the plasma of patients with pancreatic carcinoma: diagnostic utility and prognostic significance. J Clin Oncol. 1999;17:578–84.PubMed
19.
go back to reference Niedergethmann M, Rexin M, Hildenbrand R, Knob S, Sturm JW, Richter A, Post S. Prognostic implications of routine, immunohistochemical, and molecular staging in resectable pancreatic adenocarcinoma. Am J Surg Pathol. 2002;26:1578–87.PubMedCrossRef Niedergethmann M, Rexin M, Hildenbrand R, Knob S, Sturm JW, Richter A, Post S. Prognostic implications of routine, immunohistochemical, and molecular staging in resectable pancreatic adenocarcinoma. Am J Surg Pathol. 2002;26:1578–87.PubMedCrossRef
20.
go back to reference Yamamoto S, Tomita Y, Hoshida Y, et al. Prognostic significance of activated Akt expression in pancreatic ductal adenocarcinoma. Clin Cancer Res. 2004;10:2846–50.PubMedCrossRef Yamamoto S, Tomita Y, Hoshida Y, et al. Prognostic significance of activated Akt expression in pancreatic ductal adenocarcinoma. Clin Cancer Res. 2004;10:2846–50.PubMedCrossRef
21.
go back to reference Roche PA, Cresswell P. Invariant chain association with HLA-DR molecules inhibits immunogenic peptide binding. Nature. 1990;345:615–8.PubMedCrossRef Roche PA, Cresswell P. Invariant chain association with HLA-DR molecules inhibits immunogenic peptide binding. Nature. 1990;345:615–8.PubMedCrossRef
22.
go back to reference Morton PA, Zacheis ML, Giacoletto KS, Manning JA, Schwartz BD. Delivery of nascent MHC class II-invariant chain complexes to lysosomal compartments and proteolysis of invariant chain by cysteine proteases precedes peptide binding in B-lymphoblastoid cells. J Immunol. 1995;154:137–50.PubMed Morton PA, Zacheis ML, Giacoletto KS, Manning JA, Schwartz BD. Delivery of nascent MHC class II-invariant chain complexes to lysosomal compartments and proteolysis of invariant chain by cysteine proteases precedes peptide binding in B-lymphoblastoid cells. J Immunol. 1995;154:137–50.PubMed
23.
go back to reference Stein R, Mattes MJ, Cardillo TM, et al. CD74: a new candidate target for the immunotherapy of B-cell neoplasms. Clin Cancer Res. 2007;13:5556s–63s.PubMedCrossRef Stein R, Mattes MJ, Cardillo TM, et al. CD74: a new candidate target for the immunotherapy of B-cell neoplasms. Clin Cancer Res. 2007;13:5556s–63s.PubMedCrossRef
24.
go back to reference Griffiths GL, Mattes MJ, Stein R, Govindan SV, Horak ID, Hansen HJ, Goldenberg DM. Cure of SCID mice bearing human B-lymphoma xenografts by an anti-CD74 antibody-anthracycline drug conjugate. Clin Cancer Res. 2003;9:6567–71.PubMed Griffiths GL, Mattes MJ, Stein R, Govindan SV, Horak ID, Hansen HJ, Goldenberg DM. Cure of SCID mice bearing human B-lymphoma xenografts by an anti-CD74 antibody-anthracycline drug conjugate. Clin Cancer Res. 2003;9:6567–71.PubMed
25.
go back to reference Burton JD, Ely S, Reddy PK, Stein R, Gold DV, Cardillo TM, Goldenberg DM. CD74 is expressed by multiple myeloma and is a promising target for therapy. Clin Cancer Res. 2004;10:6606–11.PubMedCrossRef Burton JD, Ely S, Reddy PK, Stein R, Gold DV, Cardillo TM, Goldenberg DM. CD74 is expressed by multiple myeloma and is a promising target for therapy. Clin Cancer Res. 2004;10:6606–11.PubMedCrossRef
26.
go back to reference Michel RB, Rosario AV, Andrews PM, Goldenberg DM, Mattes MJ. Therapy of small subcutaneous B-lymphoma xenografts with antibodies conjugated to radionuclides emitting low-energy electrons. Clin Cancer Res. 2005;11:777–86.PubMed Michel RB, Rosario AV, Andrews PM, Goldenberg DM, Mattes MJ. Therapy of small subcutaneous B-lymphoma xenografts with antibodies conjugated to radionuclides emitting low-energy electrons. Clin Cancer Res. 2005;11:777–86.PubMed
27.
go back to reference Chamuleau ME, Souwer Y, Van Ham SM, et al. Class II-associated invariant chain peptide expression on myeloid leukemic blasts predicts poor clinical outcome. Cancer Res. 2004;64:5546–50.PubMedCrossRef Chamuleau ME, Souwer Y, Van Ham SM, et al. Class II-associated invariant chain peptide expression on myeloid leukemic blasts predicts poor clinical outcome. Cancer Res. 2004;64:5546–50.PubMedCrossRef
28.
go back to reference Evans DB, Rich TA, Byrd DR, et al. Preoperative chemoradiation and pancreaticoduodenectomy for adenocarcinoma of the pancreas. Arch Surg. 1992;127:1335–9.PubMed Evans DB, Rich TA, Byrd DR, et al. Preoperative chemoradiation and pancreaticoduodenectomy for adenocarcinoma of the pancreas. Arch Surg. 1992;127:1335–9.PubMed
Metadata
Title
CD74 Is a Novel Prognostic Factor for Patients with Pancreatic Cancer Receiving Multimodal Therapy
Authors
Shigenori Nagata, MD, PhD
Yu-Fen Jin, MD, PhD
Katsuhiko Yoshizato
Miki Tomoeda, DDS, PhD
Misa Song, MD
Norishige Iizuka, MD
Masanori Kitamura, MD
Hidenori Takahashi, MD, PhD
Hidetoshi Eguchi, MD, PhD
Hiroaki Ohigashi, MD, PhD
Osamu Ishikawa, MD, PhD
Yasuhiko Tomita, MD, PhD
Publication date
01-09-2009
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 9/2009
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-009-0532-3

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