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Differentiation and prognostic markers in ampullary cancer: Role of p53, MDM2, CDX2, mucins and cytokeratins.
Pathol Res Pract 2016; 212(11):1039-1047PR

Abstract

INTRODUCTION

Subclassification of ampullary adenocarcinomas into intestinal and pancreatobiliary type has prognostic and therapeutic implications. Immunohistochemical staining against specific biomarkers has been proven to be a useful adjunct in determining the exact histotype. Furthermore the immunohistochemical profile is suggestive of the molecular pathogenic mechanisms through which the tumor evolved. The aim of this study was to correlate p53, MDM2, CK7, CK20, MUC1, MUC2 and CDX2 expression in ampullary adenocarcinomas with the type of differentiation and patients' survival.

MATERIAL AND METHODS

Forty-seven radically resected ampullary adenocarcinomas were included in this study. Thirty-eight of them were eligible for survival analysis. Patients' data were retrospectively collected. All tumors were classified as intestinal or pancreatobiliary type, according to histologic criteria, and immunohistochemically stained against the aforementioned markers.

RESULTS

There were 18 intestinal and 29 pancreatobiliary type ampullary adenocarcinomas. A trend was found between intestinal type tumors and large tumor size. CK20, MUC2 and CDX2 expression was more prevalent in intestinal type tumors, while MUC1 was more frequently expressed in pancreatobiliary type tumors. Neither p53 nor MDM2 differential expression between the two histotypes reached statistical significance. Multivariate analysis indicated CK20 and MUC1 as independent predictors of the histotype. Mean and median survival was 90.3 and 55 months respectively. Overall 5-year survival rate was 48%. Survival analysis indicated TNM stage as the only independent prognostic factor. Although significant difference in survival rates among the two histotypes was implied based on survival plots, this difference could not gain statistical significance.

CONCLUSION

Immunoreactivity against CK20 and MUC1 in ampullary carcinomas is a useful adjunct to histologic examination in determining histotype. None of the immunohistochemical markers studied has prognostic significance. Future studies focused on other signaling pathways should seek further evidence of distinct tumorigenic mechanisms between histotypes of ampullary adenocarcinoma.

Authors+Show Affiliations

Third Surgical Department, "George Gennimatas" General Hospital, 154 Mesogeion Ave., PC 156 69 Athens, Greece. Electronic address: iraklisper@gmail.com.Pathology Department, "George Gennimatas" General Hospital, 154 Mesogeion Ave., PC 156 69 Athens, Greece.Second Department of Propaedeutic Surgery, "Laiko" Hospital, Athens University Medical School, 17 Ag. Thoma st., PC 11527, Greece.Second Department of Propaedeutic Surgery, "Laiko" Hospital, Athens University Medical School, 17 Ag. Thoma st., PC 11527, Greece.Pathology Department, "George Gennimatas" General Hospital, 154 Mesogeion Ave., PC 156 69 Athens, Greece.Third Surgical Department, "George Gennimatas" General Hospital, 154 Mesogeion Ave., PC 156 69 Athens, Greece.Third Surgical Department, "George Gennimatas" General Hospital, 154 Mesogeion Ave., PC 156 69 Athens, Greece.Third Surgical Department, "George Gennimatas" General Hospital, 154 Mesogeion Ave., PC 156 69 Athens, Greece.Second Department of Propaedeutic Surgery, "Laiko" Hospital, Athens University Medical School, 17 Ag. Thoma st., PC 11527, Greece.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27688085

Citation

Perysinakis, Iraklis, et al. "Differentiation and Prognostic Markers in Ampullary Cancer: Role of P53, MDM2, CDX2, Mucins and Cytokeratins." Pathology, Research and Practice, vol. 212, no. 11, 2016, pp. 1039-1047.
Perysinakis I, Minaidou E, Mantas D, et al. Differentiation and prognostic markers in ampullary cancer: Role of p53, MDM2, CDX2, mucins and cytokeratins. Pathol Res Pract. 2016;212(11):1039-1047.
Perysinakis, I., Minaidou, E., Mantas, D., Sotiropoulos, G. C., Leontara, V., Tsipras, H., ... Kouraklis, G. (2016). Differentiation and prognostic markers in ampullary cancer: Role of p53, MDM2, CDX2, mucins and cytokeratins. Pathology, Research and Practice, 212(11), pp. 1039-1047. doi:10.1016/j.prp.2016.09.004.
Perysinakis I, et al. Differentiation and Prognostic Markers in Ampullary Cancer: Role of P53, MDM2, CDX2, Mucins and Cytokeratins. Pathol Res Pract. 2016;212(11):1039-1047. PubMed PMID: 27688085.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differentiation and prognostic markers in ampullary cancer: Role of p53, MDM2, CDX2, mucins and cytokeratins. AU - Perysinakis,Iraklis, AU - Minaidou,Emilia, AU - Mantas,Dimitrios, AU - Sotiropoulos,George C, AU - Leontara,Vasileia, AU - Tsipras,Hercules, AU - Zografos,George N, AU - Margaris,Ilias, AU - Kouraklis,Gregory, Y1 - 2016/09/22/ PY - 2016/07/17/received PY - 2016/09/01/revised PY - 2016/09/09/accepted PY - 2016/10/1/pubmed PY - 2017/3/18/medline PY - 2016/10/1/entrez KW - Ampullary adenocarcinoma KW - Intestinal KW - MDM2 KW - Pancreatobiliary KW - Prognosis KW - p53 SP - 1039 EP - 1047 JF - Pathology, research and practice JO - Pathol. Res. Pract. VL - 212 IS - 11 N2 - INTRODUCTION: Subclassification of ampullary adenocarcinomas into intestinal and pancreatobiliary type has prognostic and therapeutic implications. Immunohistochemical staining against specific biomarkers has been proven to be a useful adjunct in determining the exact histotype. Furthermore the immunohistochemical profile is suggestive of the molecular pathogenic mechanisms through which the tumor evolved. The aim of this study was to correlate p53, MDM2, CK7, CK20, MUC1, MUC2 and CDX2 expression in ampullary adenocarcinomas with the type of differentiation and patients' survival. MATERIAL AND METHODS: Forty-seven radically resected ampullary adenocarcinomas were included in this study. Thirty-eight of them were eligible for survival analysis. Patients' data were retrospectively collected. All tumors were classified as intestinal or pancreatobiliary type, according to histologic criteria, and immunohistochemically stained against the aforementioned markers. RESULTS: There were 18 intestinal and 29 pancreatobiliary type ampullary adenocarcinomas. A trend was found between intestinal type tumors and large tumor size. CK20, MUC2 and CDX2 expression was more prevalent in intestinal type tumors, while MUC1 was more frequently expressed in pancreatobiliary type tumors. Neither p53 nor MDM2 differential expression between the two histotypes reached statistical significance. Multivariate analysis indicated CK20 and MUC1 as independent predictors of the histotype. Mean and median survival was 90.3 and 55 months respectively. Overall 5-year survival rate was 48%. Survival analysis indicated TNM stage as the only independent prognostic factor. Although significant difference in survival rates among the two histotypes was implied based on survival plots, this difference could not gain statistical significance. CONCLUSION: Immunoreactivity against CK20 and MUC1 in ampullary carcinomas is a useful adjunct to histologic examination in determining histotype. None of the immunohistochemical markers studied has prognostic significance. Future studies focused on other signaling pathways should seek further evidence of distinct tumorigenic mechanisms between histotypes of ampullary adenocarcinoma. SN - 1618-0631 UR - https://www.unboundmedicine.com/medline/citation/27688085/Differentiation_and_prognostic_markers_in_ampullary_cancer:_Role_of_p53_MDM2_CDX2_mucins_and_cytokeratins_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0344-0338(16)30260-6 DB - PRIME DP - Unbound Medicine ER -