Immunohistochemical Predictors for Intestinal and Pancreatobiliary Types of Adenocarcinoma of The Ampulla of Vater
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To investigate immunohistochemical predictors for intestinal and pancreatobiliary types of adenocarcinoma of ampulla of Vater and identify clinicopathological characteristics associated with the histological types and patient survival.
Immunohistochemical markers included MUC1, MUC2, MUC5AC, CDX2, CK7, and CK20. The data were analyzed by univariate and multivariate methods. The two-step cluster method was used to determine the best immunohistochemical markers to discriminate the intestinal from the pancreatobiliary type.
This study identified 9 (33.3%) intestinal and 21 (66.7%) pancreatobiliary tumors. CK7 and CDX2 achieved the highest value (= 1) as predictor markers, while CK20, MUC1, and MUC2 showed degrees of importance equal to 0.77, 0.71, and 0.68, respectively. MUC5AC did not reach 0.50 of importance. In the univariate analysis, lymph node involvement, staging (TNM), and angiolymphatic and perineural invasions were associated with histological types. The independent clinicopathological variable in the multivariate model to predict the histological type was angiolymphatic invasion (p = 0.005), OR = 17 (95% CI 2.33 to 123.83). The final model showed positive nodes (N1) associated with shorter survival (HR = 9.5; p = 0.006). Overall survival at 12, 36, and 60 months was 88.5, 67.0, and 47.6%, respectively.
CDX2 and CK7 were the immunohistochemical markers that best discriminated the intestinal from the pancreatobiliary type. Lymph node involvement had a high impact on survival and proved to be more frequent in the pancreatobiliary type.
KeywordsAmpulla of Vater Adenocarcinoma Immunohistochemistry Survival
João Paulo Lemos da Silveira Santos and João Bernardo Sancio Rocha Rodrigues: collecting data, drafting, and final approval of the work.
Carla Jorge Machado: statistical analysis, drafting, and final approval of the work.
Eduardo Paulino Junior and Paula Teixeira Vidigal: interpretation and immunohistochemical analysis, drafting and final approval of the work.
Vivian Resende: conception and design, drafting and final approval of the work.
This study is financially supported by Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG); Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ) .
Compliance with Ethical Standards
This research was approved by the Research Ethics Committee of the Federal University of Minas Gerais (UFMG), logged under protocol number CAAE 23377113.1.0000.5149.
Conflict of Interest
The authors declare that there is no conflict of interest.
- 3.Albores-Saavedra J. Tumors of the gallbladder, extrahepatic bile ducts, and ampulla of vater. in: Albores-Saavedra J, editor. Atlas of Tumor Pathology. Washington, D.C.: Armed Forces Institute of Pathology; 2000. p. 259:316.Google Scholar
- 6.de Paiva Haddad LB, Patzina RA, Penteado S, Montagnini AL, da Cunha JE, Machado MC, Jukemura J. Lymph node involvement and not the histophatologic subtype is correlated with outcome after resection of adenocarcinoma of the ampulla of vater. J Gastrointest Surg 2010; 14(4):719–28.CrossRefPubMedGoogle Scholar
- 8.Westgaard A, Tafjord S, Farstad IN, Cvancarova M, Eide TJ, Mathisen O, Clausen OP, Gladhaug IP. Pancreatobiliary versus intestinal histologic type of differentiation is an independent prognostic factor in resected periampullary adenocarcinoma. BMC Cancer 2008; 8:170.CrossRefPubMedPubMedCentralGoogle Scholar
- 9.Bronsert P, Kohler I, Werner M, Makowiec F, Kuesters S, Hoeppner J, Hopt UT, Keck T, Bausch D, Wellner UF. Intestinal-type of differentiation predicts favourable overall survival: confirmatory clinicopathological analysis of 198 periampullary adenocarcinomas of pancreatic, biliary, ampullary and duodenal origin. BMC Cancer 2013; 13: 428.CrossRefPubMedPubMedCentralGoogle Scholar
- 10.Ohike N, Kim GE, Tajiri T, Krasinskas A, Basturk O, Coban I, Bandyopadhyay S, Morohoshi T, Goodman M, Kooby DA, Sarmiento JM, Adsay NV. Intra-ampullary papillary-tubular neoplasm (IAPN): characterization of tumoral intraepithelial neoplasia occurring within the ampulla: a clinicopathologic analysis of 82 cases. Am J Surg Pathol 2010; 34(12):1731–48.CrossRefPubMedPubMedCentralGoogle Scholar
- 11.Adsay V, Ohike N, Tajiri T, Kim GE, Krasinskas A, Balci S, Bagci P, Basturk O, Bandyopadhyay S, Jang KT, Kooby DA, Maithel SK, Sarmiento J, Staley CA, Gonzalez RS, Kong SY, Goodman M. Ampullary region carcinomas: definition and site specific classification with delineation of four clinicopathologically and prognostically distinct subsets in an analysis of 249 cases. Am J Surg Pathol 2012; 36(11):1592–608.CrossRefPubMedGoogle Scholar
- 14.Schueneman A, Goggins M, Ensor J, Saka B, Neishaboori N, Lee S, Maitra A, Varadhachary G, Rezaee N, Wolfgang C, Adsay V, Wang H, Overman MJ. Validation of histomolecular classification utilizing histological subtype, MUC1, and CDX2 for prognostication of resected ampullary adenocarcinoma. Br J Cancer 2015; 113(1):64–8.CrossRefPubMedPubMedCentralGoogle Scholar
- 18.Klimstra DS, Albores-Saavedra J, Holuban RH, Zamboni G. Tumours of the ampullary region. In Boseman FT, Carneiro F, Hruban RH, Theise ND (eds) World Health Organization Classification of Tumours of the Digestive System. ed 4. Lyon: IARC; 2010;80-91.Google Scholar
- 21.Chang DK, Jamieson NB, Johns AL, Scarlett CJ, Pajic M, Chou A, Pinese M, Humphris JL, Jones MD, Toon C, Nagrial AM, Chantrill LA, Chin VT, Pinho AV, Rooman I, Cowley MJ, Wu J, Mead RS, Colvin EK, Samra JS, Corbo V, Bassi C, Falconi M, Lawlor RT, Crippa S, Sperandio N, Bersani S, Dickson EJ, Mohamed MA, Oien KA, Foulis AK, Musgrove EA, Sutherland RL, Kench JG, Carter CR, Gill AJ, Scarpa A, McKay CJ, Biankin AV. Histomolecular phenotypes and outcome in adenocarcinoma of the ampulla of Vater. J Clin Oncol 2013; 31(10):1348–56.CrossRefPubMedGoogle Scholar
- 24.Morini S, Perrone G, Borzomati D, Vincenzi B, Rabitti C, Righi D, Castri F, Manazza AD, Santini D, Tonini G, Coppola R, Onetti Muda A. Carcinoma of the ampulla of Vater: morphological and immunophenotypical classification predicts overall survival. Pancreas 2013; 42(1): 60–6.CrossRefPubMedGoogle Scholar
- 29.Reid MD, Balci1 S, Ohike N, Xue Y, Kim GE, Tajiri T, Memis B, Coban I, Dolgun A, Krasinskas AM, Basturk O, Kooby DA, Sarmiento JM, Maithel SK, El-Rayes BF, Adsay V. Ampullary carcinoma is often of mixed or hybrid histologic type: an analysis of reproducibility and clinical relevance of classification as pancreatobiliary versus intestinal in 232 cases. Mod Pathol 2016; 29: 1575–85.CrossRefPubMedGoogle Scholar
- 32.Colussi O, Voron T, Pozet A, Hammel P, Sauvanet A, Bachet JB, Vaillant JC, Rougier P, Nordlinger B, Berger A, Coriat R, Dousset B, Malka D, André T, Paye F, Aparicio T, Locher C, Cojean Zeleck D, Tchinou L, Bonnetain F, Taieb J. Prognostic score for recurrence after Whipple’s pancreaticoduodenectomy for ampullary carcinomas; results of an AGEO retrospective multicenter cohort. Eur J Surg Oncol 2015; 41(4): 520–6.CrossRefPubMedGoogle Scholar
- 33.Neoptolemos JP, Moore MJ, Cox TF, Valle JW, Palmer DH, McDonald AC, Carter R, Tebbutt NC, Dervenis C, Smith D, Glimelius B, Charnley RM, Lacaine F, Scarfe AG, Middleton MR, Anthoney A, Ghaneh P, Halloran CM, Lerch MM, Oláh A, Rawcliffe CL, Verbeke CS, Campbell F, Büchler MW. Effect of adjuvant chemotherapy with fluorouracil plus folinic acid or gemcitabine vs observation on survival in patients with resected periampullary adenocarcinoma: the ESPAC-3 periampullary cancer randomized trial. JAMA 2012; 308(2):147–56.CrossRefPubMedGoogle Scholar