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The utility of immunohistochemistry in subtyping adenocarcinoma of the ampulla of vater.
Am J Surg Pathol 2014; 38(10):1371-9AJ

Abstract

Histologic classification of ampullary carcinomas into intestinal, pancreatobiliary, or other subtypes is easily achievable in some cases but difficult in others. Immunohistochemical (IHC) stains may allow distinction between the subtypes; however, their added value to routine hematoxylin and eosin (H&E) evaluation has not been systematically evaluated. Inconsistent histologic subtyping has hampered current clinical research and therapeutic trials. In this study, a consecutive series of 105 ampullary carcinomas was subtyped first by H&E evaluation and then by the evaluation of an IHC panel composed of CK7, CK20, CDX2, MUC1, and MUC2, and the added value of IHC was analyzed. By H&E, a consensus diagnosis, defined as concordant subtyping among at least 3 of the 4 independent study pathologists, was achieved in 81 of the 105 (77%) cases. There was excellent agreement for poorly differentiated and mucinous subtypes (κ=0.72 and 0.89, respectively) but only good agreement for intestinal and pancreatobiliary subtypes (κ=0.57 and 0.48, respectively) and poor agreement for mixed subtype (κ=0.09). By IHC, CK7 showed no informative value (being positive in ≥70% of the cases in both intestinal and pancreatobiliary subtypes), whereas a subtyping schema incorporating the combination staining patterns of CK20, CDX2, MUC1, and MUC2 did. By this schema, "intestinal subtype" was defined as having (1) positive staining for CK20 or CDX2 or MUC2 and negative staining for MUC1, or (2) positive staining for CK20, CDX2, and MUC2, irrespective of the MUC1 result; and "pancreatobiliary subtype" was defined as having positive staining for MUC1 and negative staining for CDX2 and MUC2, irrespective of CK20 results. Cases not fitting one of these 3 categories were regarded as "ambiguous" immunohistochemically. By combining this schema with H&E evaluation, 97 of the 105 cases (92%) could be classified into either intestinal or pancreatobiliary subtype. In particular, immunophenotyping allowed categorization of 75% of poorly differentiated adenocarcinomas and 69% of cases with mixed histologic features as either intestinal or pancreatobiliary subtype. Most mucinous adenocarcinomas (88%) were clearly intestinal subtype by IHC. Thus, our IHC schema enhanced the subtyping of ampullary carcinoma and, in combination with H&E evaluation, allowed a dichotomous classification in 92% of the cases. Should further independent studies reaffirm our findings, this schema may serve as a valuable tool in both diagnostic and research settings.

Authors+Show Affiliations

Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Evaluation Studies
Journal Article

Language

eng

PubMed ID

24832159

Citation

Ang, Daphne C., et al. "The Utility of Immunohistochemistry in Subtyping Adenocarcinoma of the Ampulla of Vater." The American Journal of Surgical Pathology, vol. 38, no. 10, 2014, pp. 1371-9.
Ang DC, Shia J, Tang LH, et al. The utility of immunohistochemistry in subtyping adenocarcinoma of the ampulla of vater. Am J Surg Pathol. 2014;38(10):1371-9.
Ang, D. C., Shia, J., Tang, L. H., Katabi, N., & Klimstra, D. S. (2014). The utility of immunohistochemistry in subtyping adenocarcinoma of the ampulla of vater. The American Journal of Surgical Pathology, 38(10), pp. 1371-9. doi:10.1097/PAS.0000000000000230.
Ang DC, et al. The Utility of Immunohistochemistry in Subtyping Adenocarcinoma of the Ampulla of Vater. Am J Surg Pathol. 2014;38(10):1371-9. PubMed PMID: 24832159.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The utility of immunohistochemistry in subtyping adenocarcinoma of the ampulla of vater. AU - Ang,Daphne C, AU - Shia,Jinru, AU - Tang,Laura H, AU - Katabi,Nora, AU - Klimstra,David S, PY - 2014/5/17/entrez PY - 2014/5/17/pubmed PY - 2014/11/7/medline SP - 1371 EP - 9 JF - The American journal of surgical pathology JO - Am. J. Surg. Pathol. VL - 38 IS - 10 N2 - Histologic classification of ampullary carcinomas into intestinal, pancreatobiliary, or other subtypes is easily achievable in some cases but difficult in others. Immunohistochemical (IHC) stains may allow distinction between the subtypes; however, their added value to routine hematoxylin and eosin (H&E) evaluation has not been systematically evaluated. Inconsistent histologic subtyping has hampered current clinical research and therapeutic trials. In this study, a consecutive series of 105 ampullary carcinomas was subtyped first by H&E evaluation and then by the evaluation of an IHC panel composed of CK7, CK20, CDX2, MUC1, and MUC2, and the added value of IHC was analyzed. By H&E, a consensus diagnosis, defined as concordant subtyping among at least 3 of the 4 independent study pathologists, was achieved in 81 of the 105 (77%) cases. There was excellent agreement for poorly differentiated and mucinous subtypes (κ=0.72 and 0.89, respectively) but only good agreement for intestinal and pancreatobiliary subtypes (κ=0.57 and 0.48, respectively) and poor agreement for mixed subtype (κ=0.09). By IHC, CK7 showed no informative value (being positive in ≥70% of the cases in both intestinal and pancreatobiliary subtypes), whereas a subtyping schema incorporating the combination staining patterns of CK20, CDX2, MUC1, and MUC2 did. By this schema, "intestinal subtype" was defined as having (1) positive staining for CK20 or CDX2 or MUC2 and negative staining for MUC1, or (2) positive staining for CK20, CDX2, and MUC2, irrespective of the MUC1 result; and "pancreatobiliary subtype" was defined as having positive staining for MUC1 and negative staining for CDX2 and MUC2, irrespective of CK20 results. Cases not fitting one of these 3 categories were regarded as "ambiguous" immunohistochemically. By combining this schema with H&E evaluation, 97 of the 105 cases (92%) could be classified into either intestinal or pancreatobiliary subtype. In particular, immunophenotyping allowed categorization of 75% of poorly differentiated adenocarcinomas and 69% of cases with mixed histologic features as either intestinal or pancreatobiliary subtype. Most mucinous adenocarcinomas (88%) were clearly intestinal subtype by IHC. Thus, our IHC schema enhanced the subtyping of ampullary carcinoma and, in combination with H&E evaluation, allowed a dichotomous classification in 92% of the cases. Should further independent studies reaffirm our findings, this schema may serve as a valuable tool in both diagnostic and research settings. SN - 1532-0979 UR - https://www.unboundmedicine.com/medline/citation/24832159/The_utility_of_immunohistochemistry_in_subtyping_adenocarcinoma_of_the_ampulla_of_vater_ L2 - http://dx.doi.org/10.1097/PAS.0000000000000230 DB - PRIME DP - Unbound Medicine ER -