The Role of Maspin Expression as Diagnostic Tissue Marker in Pancreaticoduodenal Malignant Tumors and Benign Lesions




Immunohistochemistry, Pancreatic carcinoma, Maspin


BACKGROUND: Maspin (a tumor suppressor gene) is down-regulated in breast, prostate, gastric, and melanoma. Although it is not detected in normal pancreatic tissue, it is over-expressed in pancreatic cancer suggesting that maspin may play different activities in different cell types. Pancreatic ductal adenocarcinoma (PC) acquires maspin expression through hypomethylation of its promoter.

AIM: Because the discrimination between ampullary and periampullary carcinomas is challenging in advanced cases, this inspired us to search for the use of maspin expression to discriminate between ampullary carcinoma (AC), PC, duodenal adenocarcinoma (DC), and other confusing benign and inflammatory pancreatic lesions.

METHODS: Immunostaining for maspin was performed for 80 pancreaticoduodenal lesions. Sixty cases were malignant: 48 cases of pancreatic epithelial tumor (41 PC and 7 solid pseudopapillary neoplasm), 9 AC, and 3 DC. Twenty cases were non-malignant: 12 inflammatory (chronic pancreatitis), 5 benign neoplastic (serous cystadenomas), and 3 normal pancreatic tissue. Cytoplasmic and/or nuclear staining was considered positive as: Focally positive (5–50% of tumor cells), diffusely positive (>50% of tumor cells), or negative (<5% tumor cells).

RESULTS: Maspin expression (positive/negative), distribution (focal/diffuse), and nuclear expression are significantly different between PC, solid pseudopapillary neoplasm, AC, and DC. PC shows significantly higher expression with more diffuse positivity and more nuclear expression than other malignant groups. Forty cases of PC (40/41) (97.6%) showed positive expression; 28 of them (28/40) (70%) showed diffuse expression and 82.5% (33 cases) showed nuclear and cytoplasmic expression. Only one case (14.3%) (1/7) of solid pseudopapillary neoplasm showed positive focal cytoplasmic expression. Three AC cases (3/9) (33.3%) showed positive focal cytoplasmic expression. Two cases of DC (2/3) (66.7%) showed positive focal cytoplasmic expression. Maspin expression shows significant positive correlation with poor prognostic variables as tumor grade, lymphovascular invasion, T stage of PC. Minority of chronic pancreatitis and benign lesions are maspin positive with significant difference from the malignant groups.

CONCLUSION: Our results suggest that maspin can be of value in differentiating pancreatic adenocarcinoma from ampullary carcinoma, duodenal adenocarcinoma, and other confusing lesions as chronic pancreatitis.


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Sunnapwar AA, Nagar A, Katre R, Khanna L, Sayana HP. Imaging of ampullary and periampullary conditions. J Gastrointest Abdom Radiol. 2021;4(03):214-28. DOI:

Komine R, Kojima M, Ishi G, Kudo M, Sugimoto M, Kobayashi S, et al. Recognition and pathological features of periampullary region adenocarcinoma with an indeterminable origin. Cancer Med. 2021;10(11):3499-510. PMid:34008914 DOI:

Bosman FT, Carneiro F, Hruban RH. WHO Classification of Tumours of the Digestive System. Vol. 3. Lyon, France: IARC Press, World Health Organization Classification of Tumours; 2010.

Chugh S, Barkeer S, Rachagani S, Nimmakayala RK, Perumal N, Pothuraju R, et al. Disruption of C1galt1 gene promotes development and metastasis of pancreatic adenocarcinomas in mice. Gastroenterology. 2018;155(5):1608-24. PMid:30086262 DOI:

Mizrahi JD, Surana R, Valle JW, Shroff RT. Pancreatic cancer. Lancet. 2020;395:2008-20. DOI:

Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics. CA Cancer J Clin. 2021;71(1):7-33. PMid:33433946 DOI:

McGuigan A, Kelly P, Turkington RC, Jones C, Coleman HG, McCain RS. Pancreatic cancer: A review of clinical diagnosis, epidemiology, treatment and outcomes. World J Gastroenterol. 2018;24(43):4846-61. PMid:30487695 DOI:

Berardi R, Morgese F, Onofri A, Mazzanti P, Pistelli M, Ballatore Z, et al. Role of maspin in cancer. Clin Transl Med. 2013;2(1):8. PMid:23497644 DOI:

Nash JW, Bhardwaj A, Wen P, Frankel WL. Maspin is useful in the distinction of pancreatic adenocarcinoma from chronic pancreatitis: A tissue microarray based study. Appl Immunohistochem Mol Morphol. 2007;15(1):59-63. PMid:17536309 DOI:

Basturk O, Coban I, Adsay NV. Pancreatic cysts: Pathologic classification, differential diagnosis, and clinical implications. Arch Pathol Lab Med. 2009;133(3):423-38. PMid:19260748 DOI:

Nagtegaal ID, Odze RD, Klimstra D, Paradis V, Rugge M, Schirmacher P, et al. The 2019 WHO classification of tumours of the digestive system. Histopathology. 2020;76(2):182-8. PMid:31433515 DOI:

Chun YS, Pawlik TM, Vauthey JN. 8th Edition of the AJCC cancer staging manual: Pancreas and hepatobiliary cancers. Ann Surg Oncol 2018;25(4):845-7. PMid:28752469 DOI:

Cao D, Zhang Q, Wu L, Salaria SN, Winter JW, Hruban RH, et al. Prognostic significance of maspin in pancreatic ductal adenocarcinoma: Tissue microarray analysis of 23 surgically resected cases. Modern Pathol. 2007;20(5):570-8. PMid:17396143 DOI:

Rawla P, Sunkara T, Gaduputi V. Epidemiology of pancreatic cancer: Global trends, etiology and risk factors. World J Oncol. 2019;10(1):10-27. PMid:30834048 DOI:

Futscher BW, Oshiro MM, Wozniak RJ, Holtan N, Hanigan CL, Duan H, et al. Role for DNA methylation in the control of cell type specific maspin expression. Nat Genet. 2002;31(2):175-9. PMid:12021783 DOI:

Ngamkitidechakul C, Burke JM, O’Brien WJ, Twining SS. Maspin: Synthesis by human cornea and regulation of in vitro stromal cell adhesion to extracellular matrix. Invest Ophthalmol Vis Sci 2001;42(13):3135-41. PMid:11726614

Lim YJ, Lee JK, Jang WY, Song SY, Lee KT, Paik SW, et al. Prognostic significance of maspin in pancreatic ductal adenocarcinoma. Korean J Intern Med 2004;19(1):15-8. PMid:15053038 DOI:

Xin W, Yun KJ, Ricci F, Zahurak M, Qiu W, Su GH, et al. MAP2K4/MKK4 expression in pancreatic cancer: Genetic validation of immunohistochemistry and relationship to disease course. Clin Cancer Res. 2004;10(24):8516-20. PMid:15623633 DOI:

Oh YL, Song SY, Ahn G. Expression of maspin in pancreatic neoplasms: Application of maspin immunohistochemistry to the differential diagnosis. Appl Immunohistochem Mol Morphol. 2002;10(1):62-6. PMid:11893038 DOI:

Liu H, Shi J, Anandan V, Wang HL, Diehl D, Blansfield J, et al. Reevaluation and identification of the best immunohistochemical panel (pVHL, Maspin, S100P, IMP-3) for ductal adenocarcinoma of the pancreas. Arch Pathol Lab Med. 2012;136(6):601-9. PMid:22646265 DOI:

Blandamura S, D’alessandro E, Guzzardo V, Giacomelli L, Moschino P, Parenti A, et al. Maspin expression in adenocarcinoma of the ampulla of vater: Relation with clinicopathological parameters and apoptosis. Anticancer Res. 2007;27(2):1059-65. PMid:17465244

Helal DS, El-Guindy DM. Maspin expression and subcellular localization in invasive ductal carcinoma of the breast: Prognostic significance and relation to microvessel density. J Egypt Natl Canc Inst. 2017;29(4):177-83. PMid:29126758 DOI:

Tsoli E, Tsantoulis PK, Papalambros A, Perunovic B, England D, Rawlands DA, et al. Simultaneous evaluation of maspin and CXCR4 in patients with breast cancer. J Clin Pathol. 2007;60(3):261-6. PMid:16751302 DOI:

Lee MJ, Suh CH, Li ZH. Clinicopathological significance of maspin expression in breast cancer. J Korean Med Sci. 2006;21(2):309-14. PMid:16614520 DOI:

Umekita Y, Yoshida H. Expression of maspin is up-regulated during the progression of mammary ductal carcinoma. Histopathology. 2003;42(6):541-5. PMid:12786889 DOI:

Ohike N, Maass N, Mundhenke C, et al. Clinicopathological significance and molecular regulation of maspin expression in ductal adenocarcinoma of the pancreas. Cancer Lett. 2003;199(2):193-200. PMid:12969792 DOI:

Terashima M, Maesawa C, Oyama K, Ohtani S, Akiyama Y, Ogasawara S, et al. Gene expression profiles in human gastric cancer: Expression of maspin correlates with lymph node metastasis. Br J Cancer. 2005;92(6):1130-6. PMid:15770218 DOI:

Maass N, Hojo T, Ueding M, Lüttges J, Klöppel G, Jonat W, et al. Expression of the tumor suppressor gene Maspin in human pancreatic cancers. Clin Cancer Res. 2001;7(4):812-7. PMid:11309327

Aksoy-Altinboga A, Baglan T, Umudum H, Ceyhan K. Diagnostic value of S100p, IMP3, Maspin, and pVHL in the differantial diagnosis of pancreatic ductal adenocarcinoma and normal/chronic pancreatitis in fine needle aspiration biopsy. J Cytol. 2018;35(4):247-51. Mid:30498299 DOI:

Mamdouh MM, Okasha H, Shaaban HA, Hafez NH, El-Gemeie EH. Role of maspin, CK17 and Ki-67 immunophenotyping in diagnosing of pancreatic ductal adenocarcinoma in endoscopic ultrasound-guided fine needle aspiration cytology. Asian Pac J Cancer Prev. 2021;22:3299-307. PMid:34711007 DOI:

Tarafa G, Villanueva A, Farré L, Rodríguez J, Musulén E, Reyes G, et al. DCC and SMAD4 alterations in human colorectal and pancreatic tumor dissemination. Oncogene. 2000;19:546-55. PMid:10698524 DOI:




How to Cite

ElEsawy Y, Khaled E, Biomy B, Elsheikh S, El-Yasergy D. The Role of Maspin Expression as Diagnostic Tissue Marker in Pancreaticoduodenal Malignant Tumors and Benign Lesions. Open Access Maced J Med Sci [Internet]. 2022 May 25 [cited 2023 Mar. 22];10(A):1042-50. Available from: