Histopathological study of intraductal papillary mucinous tumor of the pancreas: special reference to the roles of Survivin and p53 in tumorigenesis of IPMT.
OBJECTIVE
In this study, we investigated the tissue expression of Survivin, p53, and Bcl-2 in intraductal papillary-mucinous tumor (IPMT) of the pancreas to identify their roles in tumorigenesis of IPMT, and examined their correlations with tumor cell apoptosis and proliferation in IPMT. The diagnostic values of the expression of Survivin, p53, and Bcl-2 and the apoptotic index (AI) and Ki-67 labeling index (Ki-67 LI) in IPMT were also examined.


METHODS
Twenty-two lesions from 17 patients with IPMT, including 12 benign (IPMT Adenoma) and 10 malignant (IPMT Carcinoma In Situ [CIS] (n = 4) and Invasive IPMT (n = 6) lesions, were immunostained for Survivin, p53, Bcl-2 and Ki-67. The apoptotic cells were detected by the Apop Tag(R) In Situ Oligo Ligation (ISOL) method.


RESULTS
The immunoreactivities for Survivin and p53 significantly increased in the transition from IPMT Adenoma to IPMT CIS (p < 0.05 for both). This transition was associated with a significant decrease in tumor cell apoptosis ( p < 0.001). The expression of Survivin was significantly associated with AI in IPMT ( p < 0.01), but not with Ki-67 LI. The expressions of Survivin and p53, and AI and Ki-67 LI were also significantly different between benign IPMT and malignant IPMT. Bcl-2 was not expressed in IPMT.


CONCLUSIONS
These results suggest that Survivin and p53 may play important roles in the transition from IPMT Adenoma to IPMT CIS. This transition is accompanied by a significant decrease in tumor cell apoptosis. Survivin is significantly associated with the change in AI in IPMT. The immunohistochemical detection of Survivin and p53 as well as the determination of the AI and Ki-67 LI have useful roles in the diagnosis of IPMT.
Jinfeng
Ma
M
First Department of Surgery, Yamagata University School of Medicine, Yamagata, Japan.
Kimura
Wataru
W
Sakurai
Fumiaki
F
Moriya
Toshiyuki
T
Takeshita
Akiko
A
Hirai
Ichiro
I
D002288:Adenocarcinoma, Mucinous / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D000236:Adenoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D002278:Carcinoma in Situ / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D002291:Carcinoma, Papillary / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D002471:Cell Transformation, Neoplastic; D003937:Diagnosis, Differential; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis*; D009363:Neoplasm Proteins; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D016159:Tumor Suppressor Protein p53