Differentiation and prognostic markers in ampullary cancer: Role of p53, MDM2, CDX2, mucins and cytokeratins.
BACKGROUND
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.


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.


CONCLUSIONS
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.
Third Surgical Department, "George Gennimatas" General Hospital, 154 Mesogeion Ave., PC 156 69 Athens, Greece. Electronic address: iraklisper@gmail.com.
Iraklis
I
Perysinakis
Pathology Department, "George Gennimatas" General Hospital, 154 Mesogeion Ave., PC 156 69 Athens, Greece.
Emilia
E
Minaidou
Second Department of Propaedeutic Surgery, "Laiko" Hospital, Athens University Medical School, 17 Ag. Thoma st., PC 11527, Greece.
Dimitrios
D
Mantas
Second Department of Propaedeutic Surgery, "Laiko" Hospital, Athens University Medical School, 17 Ag. Thoma st., PC 11527, Greece.
George C
GC
Sotiropoulos
Pathology Department, "George Gennimatas" General Hospital, 154 Mesogeion Ave., PC 156 69 Athens, Greece.
Vasileia
V
Leontara
Third Surgical Department, "George Gennimatas" General Hospital, 154 Mesogeion Ave., PC 156 69 Athens, Greece.
Hercules
H
Tsipras
Third Surgical Department, "George Gennimatas" General Hospital, 154 Mesogeion Ave., PC 156 69 Athens, Greece.
George N
GN
Zografos
Third Surgical Department, "George Gennimatas" General Hospital, 154 Mesogeion Ave., PC 156 69 Athens, Greece.
Ilias
I
Margaris
Second Department of Propaedeutic Surgery, "Laiko" Hospital, Athens University Medical School, 17 Ag. Thoma st., PC 11527, Greece.
Gregory
G
Kouraklis
D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014670:Ampulla of Vater / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D000071616:CDX2 Transcription Factor / Q000378:metabolism; D002454:Cell Differentiation; D003138:Common Bile Duct Neoplasms / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D007633:Keratins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009077:Mucins / Q000378:metabolism; D011379:Prognosis; D016016:Proportional Hazards Models; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D055815:Young Adult
D014408:Biomarkers, Tumor; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D009077:Mucins; D016159:Tumor Suppressor Protein p53; D007633:Keratins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2
Ampullary adenocarcinoma; Intestinal; MDM2; Pancreatobiliary; Prognosis; p53