Immunohistochemical study of genetic alterations in intraductal and invasive ductal tumors of the pancreas.

BACKGROUND/AIMS: Multiple genetic alterations are involved in the development of pancreatic neoplasm. Here we investigated the incidence of p53, ras, bcl-2 and c-erbB-2 gene alterations in intraductal papillary-mucinous tumors and invasive ductal adenocarcinoma of the pancreas by immunohistochemical method to identify and analyze their relationship in terms of these genetic alterations. METHODOLOGY: Fifty-four pancreatic lesions, including 18 benign (hyperplasia (3) and intraductal papillary adenoma (15)), and 16 malignant (carcinoma in situ (2) and intraductal papillary adenocarcinoma (14)) cases of intraductal papillary-mucinous tumor; and 20 cases of invasive ductal adenocarcinoma, were immunostained by avidin-biotin peroxidase conjugate method. RESULTS: p53 and rasp21 expressions were significantly greater in malignant intraductal (P < 0.01, P < 0.05) and invasive ductal (P < 0.01, P < 0.01) tumors than in benign intraductal papillary-mucinous tumors; while bcl-2 and c-erbB-2 expressions were significantly greater in invasive ductal adenocarcinoma than both benign (P < 0.01, P < 0.05) and malignant (P < 0.05, P < 0.05) intraductal papillary-mucinous tumors. CONCLUSIONS: Different groups of genetic alterations are involved in different phases of pancreatic tumorigenesis. p53 and ras gene alterations occur at an early stage during the development of intraductal papillary-mucinous tumor, while additional alterations of bcl-2 and c-erbB-2 occur during the development of invasive ductal adenocarcinoma of the pancreas.     

Minute invasive ductal carcinoma of the residual pancreas after distal pancreatectomy for intraductal papillary-mucinous tumor

Summary Our report describes a 66-yr-old man who underwent surgical resection of the pancreas twice within a period of 3 yr for primary and recurrent intraductal papillary mucinous tumors (IPMTs). During the second operation, a minute invasive ductal carcinoma (IDC) was accidentally discovered in the resected specimen of the residual pancreas. The similarity and continuity between this IDC and recurrent IPMT were not recognized histologically. A solid tumor was found in the hepatoduodenal ligament 3 mo after the second operation. We performed a third operation, performing laparotomy and intra-operative radiotherapy, but could not extirpate the tumor. A biopsy specimen obtained from the tumor during this third operation revealed adenocarcinoma, and the patient later died because of tumor progression. We immunohistochemically analyzed the expression of HER-2/neu, Smad4, p16, p21, p53, mucin immunophenotypes and the Ki-67 labeling index in this series of pancreatic-duct neoplasias. Overexpression of HER-2/neu and loss of Smad4 were detected in the minute IDC, which was very different from the immunohistochemical features of both the primary and recurrent IPMTs. The IDC also showed a MUC1-positive/MUC2-negative phenotype. Therefore, we suggest that de novo IDC may occur in IPMT patients, especially those with multiple tumor recurrence. The present case may be helpful in understanding the pathogenesis of pancreatic duct lesions.     

P53 mutation but not p16/MTS1 mutation occurs in intraductal papillary mucinous tumors of the pancreas

BACKGROUND/AIMS: Intraductal papillary mucinous tumors of the pancreas are rare lesions, which typically show a benign clinical course. However, some of these tumors have a malignant nature and grow in an invasive manner. The purpose of the study was to determine the prevalence of p53-, p16/MTS1- and K-ras mutations in benign and malignant intraductal papillary mucinous tumors with intent to value their importance for tumor progression. METHODOLOGY: Thirteen different archival tumor specimens were obtained at the Department of Pathology, University of Ulm. Three cases showed an invasive component of the tumor. Genomic DNA was extracted after laser capture microdissection of tumor cells from paraffin-embedded tissue sections. The corresponding sequences of p53 (exon 5, 6, 7, 8) and p16/MTS1 (exon 2) were amplified by polymerase chain reaction and subjected to single strand conformation polymorphism analysis. Codon 12 of K-ras was analyzed by the enrichment polymerase chain reaction-restriction fragment length polymorphism method. Positive samples were further investigated by sequencing. RESULTS: K-ras mutations occurred in benign and malignant intraductal papillary mucinous tumors (4/13), whereas an alteration of the coding p53 gene sequence could only be detected in the intraductal and invasive component of one malignant tumor. None of the tissue specimens revealed mutations in exon 2 of p16/MTS1. CONCLUSIONS: In contrast to K-ras mutations, alterations in the p53 gene may characterize ductal papillary mucinous carcinomas, which could be of major interest for their early diagnosis. The lack of mutations in the p16/MTS1 gene suggests that other genes may be involved in the formation of intraductal papillary mucinous neoplasias.     

Intraductal papillary mucinous neoplasms of the pancreas: an analysis of protein expression and clinical features

Background/Purpose

The molecular pathology of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas has not been well characterized, and there are no reliable markers to predict the presence of associated invasive carcinoma in patients with IPMNs. We investigated the clinicopathologic characteristics of 37 IPMNs and the immunohistochemical findings of these tumors to investigate the malignancy of IPMNs.

Methods

Between May 1992 and September 2003, 37 patients with IPMNs, 24 with adenoma and 13 with carcinoma, underwent pancreatic resections at Sapporo Medical University Hospital, Japan. In tumor specimens from these patients, we immunohistochemically analyzed the expression of p53 protein, proliferating-cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), matrix metalloproteinase-7 (MMP-7), and E-cadherin. Clinical features and follow-up after resection were recorded.

Results

Aberrant expression of the proteins examined was frequently observed. Namely, there were significant differences in the expression of MMP-7 according to clinicopathological characteristics. Positive expression of MMP-7 was found in all of nine patients with infiltrating ductal pancreatic adenocarcinoma (IDC) and in all of seven patients with invasive intraductal papillary mucinous adenocarcinoma (IC-IPMC); however, 33.3% of patients with noninvasive IPMA, 58.3% of patients with intraductal papillary mucinous adenoma (IPMA), and all normal pancreatic tissues were negative for MMP-7; differences which were statistically significant (P < 0.05).

Conclusions

Our current results indicate that MMP-7 may play a significant role in the progression of noninvasive to invasive IPMC.     

Clinical importance of precursor lesions in the pancreas

Three distinct noninvasive precursor lesions to invasive ductal adenocarcinoma of the pancreas have been described. These include the mucinous cystic neoplasm, intraductal papillary mucinous neoplasm, and pancreatic intraepithelial neoplasia. The early detection and treatment of these lesions can interrupt the progression of a curable noninvasive precursor to an almost uniformly deadly invasive cancer.     

MUC1 overexpression is the most reliable marker of invasive carcinoma in intraductal papillary-mucinous tumor (IPMT)

BACKGROUND/AIMS: To clarify the development of pancreatic cancer we performed immunohistochemical analysis of the presence of the major apomucin and cell-cycle regulatory proteins using the tissues of IPMT and ductal adenocarcinoma (DC) of the pancreas. METHODOLOGY: Formalin-fixed and paraffin-embedded tissues of 24 IPMT and 21 DC cases were subjected to immunohistochemical staining for MUC1, MUC2, p16, p53 and DPC4. According to the WHO classification, there were 10 intraductal papillary-mucinous adenomas (IPMA); 3 borderline intraductal papillary-mucinous neoplasms (IPMB); 4 intraductal papillary-mucinous carcinomas (IPMC), non-invasive type (nIPMC); 4 IPMCs with invasive muci nous carcinoma (IPMC/muc); and 3 IPMCs with invasive tubular adenocarcinoma (IPMC/tub). RESULTS: MUC1 expression was seen in 6 of 7 invasive IPMCs (86%) and in all DCs (100%). MUC2 was only seen in non-invasive IPMT and in a part of IPMC/muc. p53 nuclear staining was positive only in 3 of 7 invasive IPMCs (43%) and 9 of 21 DCs (43%). DPC4 nuclear expression was positive in almost all cases of non-invasive IPMT, but negative or reduced in 4 of 7 invasive IPMCs (57%), and 14 of 21 DCs (67%). CONCLUSIONS: MUC1 overexpression is considered to be the most sensitive and specific marker of invasive carcinoma, followed by DPC4 and p53 with less sensitivity.     

Immunohistochemical analysis of expression of molecular biologic factors in intraductal papillary-mucinous tumors of pancreas--diagnostic and biologic significance.

BACKGROUND/AIMS: In this study we investigated the expressions of molecular biologic factors, p53, rasp21, bcl-2, c-erbB-2, and Ki-67 by immunohistochemical method in intraductal papillary-mucinous tumor of the pancreas to identify their diagnostic values and to determine their relations to the degree of histopathologic abnormalities. METHODOLOGY: Thirty-eight different histologic lesions from 28 patients of intraductal papillary-mucinous tumor of the pancreas, comprising normal pancreatic duct (n = 6), intraductal papillary hyperplasia (n = 6), intraductal adenoma (n = 15), and intraductal carcinoma (n = 11) were immunostained by the avidin-biotin peroxidase conjugate method. RESULTS: p53 and Ki-67 expressions were significantly greater in malignant intraductal papillary-mucinous tumor than in their benign counterpart (p = < 0.0001), while rasp21 showed gradual increase in the frequency of expression from normal pancreatic duct (0%), to intraductal hyperplasia (16.7%), to intraductal adenoma (26.7%), and ultimately to intraductal carcinoma (63.6%). bcl-2 and c-erbB-2 were not expressed in any lesions. CONCLUSIONS: These results suggest that p53 and Ki-67 expressions have significant diagnostic values in differentiating benign intraductal papillary-mucinous tumors from malignant ones and thus can facilitate in the pre-operative planning of treatment in individual cases. Secondly, gradual stepwise increase in the frequency of rasp21 expression with increasing degree of cellular atypia supports the presence of adenoma-carcinoma sequence in the carcinogenesis of this tumor.     

Sarcomatoid carcinoma of common bile duct: a case report

Sarcomatoid carcinomas (carcinosarcomas) are rare lesions in the hepatobiliary pancreatic system. We present an extremely rare case of sarcomatoid carcinoma of the common bile duct. The tumor showed a biphasic pattern of intermixed carcinomatous (adenocarcinoma) and sarcomatoid elements (spindle and giant cells). By immunohistochemical staining, cytokeratin and vimentin were demonstrated in the sarcomatoid component. The proliferative activity and the oncoproteins expressed by the tumor were investigated by the PCNA, Ki-67, p53 and Bcl-2 in different tumor fields. Overall, the intensities of PCNA and p53 were moderate in the sarcomatoid component, but mild in the carcinomatous component. However, Ki-67 and Bcl-2 were both negative in the carcinomatous and sarcomatoid components. The possible histogenensis of sarcomatoid carcinoma of the common bile duct is discussed. We report upon an additional extremely rare case of sarcomatoid carcinoma arising in the common bile duct together with its immunohistochemical characteristics, and give details of its proliferative activity and oncoprotein expression.     

Expression of Ki-67, p53, and K-ras in chronic pancreatitis and pancreatic ductal adenocarcinoma

AIM: To examine surgical specimens of pancreas with either chronic pancreatitis or pancreatic cancer in order to study whether ductal hyperplasia and dysplasia in pancreas represent precursor lesions for pancreatic cancer. METHODS: We examined expression of Ki-67, CEA, p53, and K-ras, in the surgical specimens of pancreas with adenocarcinomas (n= 11) and chronic pancreatitis (n = 12). Cellular proliferation was assessed by Ki-67 proliferation index using the proliferation marker Ki-67. In specimens with pancreas cancer, we divided pancreas epithelium into normal (n = 7), ductal hyperplasia (n = 3), dysplasia (n = 4), and cancerous lesion (n = 11) after hematoxylin and eosin staining, Ki-67, and CEA immunohistochemical staining. In cases with chronic pancreatitis, the specimen was pathologically examined as in cases with pancreas cancer, and they were also determined as normal (n = 10), ductal hyperplasia (n = 4), or dysplasia (n = 5). p53 and K-ras expression were also studied by immunohistochemical staining. RESULTS: In pancreatic cancer, the Ki-67 index was 3.73±3.58 in normal site, 6.62±4.39 in ductal hyperplasia, 13.47±4.02 in dysplasia and 37.03±10.05 in cancer tissue, respectively. Overall, p53 was positive in normal ducts, ductal hyperplasia, dysplasia, and carcinoma cells in 0 of 14 (0%), 0 of 7(0%), 7 of 9 (78%), and 10 of 11 (91%), respectively, and K-ras was positive in 0 of 8 (0%), 1 of 3 (33%), 4 of 6 (67%), 4 of 5 (80%), respectively. CONCLUSION: Our results favorably support the hypothesis that ductal hyperplasia and dysplasia of the pancreas might be precursor lesions for pancreas cancer. Further evaluation of oncogenes by the molecular study is needed.     

Immunohistochemical analysis of molecular biological factors in intraductal papillary-mucinous tumors and mucinous cystic tumors of the pancreas

BACKGROUND: To investigate the malignancy and differentiation of intraductal papillary-mucinous tumors (IPMTs) and mucinous cystic tumors (MCTs) of the pancreas, clinicopathologic characteristics and immunohistochemical features were analyzed. METHODS: The clinicopathologic characteristics and immunohistochemical features of 24 patients with IPMT and 8 with MCT who underwent pancreatic resections at our hospital were examined. Immunohistochemical features analyzed included expression of p53 protein, proliferating cell nuclear antigen, integrins, interleukin-1 receptor type I, and hormone-associated receptors, and the factors correlated with malignancy were identified by multiple logistic regression. RESULTS: Among the IPMTs, there were 16 intraductal papillary adenomas, 5 intraductal papillary adenocarcinomas, and 3 moderate dysplasias. Among the MCTs, there were 6 mucinous cyst adenomas and 2 mucinous cyst adenocarcinomas. Multivariate analysis revealed that of the clinicopathologic characteristics, only the presence of mural nodules (odds ratio (OR) 7.12, P = 0.044) was independently correlated with the malignancy of IPMTs, and that of the immunohistochemical features, only alpha integrin subunit expression was independently correlated with malignancy of pancreatic mucinous tumors (OR 15.6, P = 0.036), especially IPMTs (OR 35.7, P = 0.012). CONCLUSION: These results indicate that alpha-containing integrin expression can be a significant marker of malignancy in pancreatic mucinous tumors.     

Biliary papillary tumors share pathological features with intraductal papillary mucinous neoplasm of the pancreas

Recently, attention has been drawn to papillary neoplasm of the pancreatobiliary systems. In the pancreas, the disease entity of intraductal papillary mucinous neoplasm (IPMN-P) is widely recognized. In contrast, the pathological characteristics of biliary papillary tumors, such as biliary papilloma(tosis) and papillary cholangiocarcinoma, have not yet been well documented. In this study, we compared the pathological features and post-operative prognosis among biliary papillary tumors (10 cases of biliary papilloma(tosis) and 22 cases of papillary cholangiocarcinoma), conventional non-papillary cholangiocarcinoma (15 cases), and IPMN-P (31 cases). Macroscopically, all biliary papillary tumors were characterized by the prominent intraductal papillary proliferation, and macroscopic mucin-hypersecretion was seen in 9 of 32 cases (28%). Histologically, biliary papillary tumors consisted of three types of tumor cells (pancreaticobiliary, intestinal and gastric types), whereas only the pancreaticobiliary type was observed in non-papillary cholangiocarcinoma. Immunohistochemically, biliary papillary tumors were characterized by the common expression of MUC2, CDX2 and cytokeratin 20. In addition, biliary papillary tumors could be associated with two types of invasive lesions: tubular adenocarcinoma (9 cases) and mucinous carcinoma (5 cases). Patients with tubular adenocarcinoma had a poor prognosis compared to non-invasive papillary tumor or papillary tumor with mucinous carcinoma. These pathological characteristics and the survival status of biliary papillary tumors were different from those of non-papillary cholangiocarcinoma, and rather closely resembled those of IPMN-P. In conclusion, biliary papillary tumors may be the biliary counterpart (intraductal papillary neoplasm of the bile duct) of IPMN-P.     

Pancreatic ductal adenocarcinomas with multiple large cystic structures: A clinicopathologic and immunohistochemical study of seven cases

Background/objectivesPancreatic ductal adenocarcinoma (PDA) with cystic change is classified into several types according to the features of the cysts; however, those tumors do not constitute a uniform group, and the classification is controversial. In this study, we have described a series of cystic PDAs that show distinctive and previously unreported morphologic and immunohistochemical features.MethodsWe analyzed 200 cases of PDA treated surgically at a single institution, and extracted the clinical and histopathological features of 7 tumors showing multiple large cystic (MLC) structure.ResultsPreoperative radiographic images revealed a multilocular mass in the pancreas which was similar to intraductal papillary mucinous neoplasm or mucinous cystic neoplasm. These tumors were associated with more than 5 large cystic structures and numerous intratumoral microcysts lined by epithelial cells with various degrees of atypia. The average maximal diameter of the cysts (3.7 cm) was much larger than that of previously reported. Immunohistochemically, the cyst-lining epithelia were almost negative for mucin core protein (MUC) 1, MUC2, and MUC6, and showed only focal staining for MUC5AC. Maspin, CEA, and p53 were strongly positive, and the Ki-67 labeling index was high in both cells in solid areas and cyst-lining epithelia.ConclusionWe considered the MLC structures in PDA to be a mixture of ectatic neoplastic glands and retention cysts with ductal cancerization or pancreatic intraepithelial neoplasia (PanIN); however, they might represent a new entity of cystic PDA because of the unusually large size of the dilated cysts.     

Clinical results of extended lymphadenectomy and intraoperative radiotherapy for pancreatic adenocarcinoma

BACKGROUND/AIMS: The efficacy of extended lymphadenectomy and intraoperative radiotherapy for resectable pancreatic cancer is controversial. The objective of this study was to clarify the surgical outcome after pancreatic resection with extended lymphadenectomy or intraoperative radiotherapy in patients with pancreatic adenocarcinoma. METHODOLOGY: Between 1992 and 2002, 105 patients with pancreatic adenocarcinoma undergoing surgical resection were retrospectively analyzed. Eighty-eight patients had invasive ductal adenocarcinoma and 17 had invasive intraductal papillary mucinous adenocarcinoma. Seventy-six patients underwent pancreatic resection with extended lymphadenectomy and 44 received 20 Gy intraoperative radiotherapy. RESULTS: Patients with invasive intraductal papillary mucinous adenocarcinoma had a similar prognosis to those with invasive ductal adenocarcinoma. There was no significant difference in survival (p = 0.86) between patients with and without extended lymphadenectomy. There was no significant difference in survival (p = 0.053) between patients with and without intraoperative radiotherapy. Patients without lymph node metastasis had a significantly better prognosis (p = 0.0015) than those with nodal involvement. CONCLUSIONS: Neither extended lymphadenectomy nor intraoperative radiotherapy showed a survival advantage in patients with resectable pancreatic adenocarcinoma. Pancreatic cancer patients without nodal involvement had a significantly better prognosis than those with nodal involvement.     

Expression of COX-2, PCNA, Ki-67 and p53 in gastrointestinal stromal tumors and its relationship with histopathological parameters

AIM： To investigate the expression of Cyclooxygenase-2 （COX-2）, proliferating cell nuclear antigen （PCNA）, Ki-67 and p53 in gastrointestinal stromal tumors （GISTs） and its relationship with histopathological parameters.
METHODS： Twenty-five GISTs were examined by light microscopy and immunohistochemistry, c-kit, CD34, SMA, S-100 protein, COX-2, PCNA, Ki-67 and p53 were detected immunohistochemically and the relationship was evaluated among histopathologic parameters such as mitotic index （MI）, tumor grade, tumor size, COX-2, PCNA, Ki-67 and p53.
RESULTS： COX-2 protein expression was found in 19 of 25 （76%） of the tumors, and expression was noted in the cytoplasm of the tumor cells, p53 was significantly related to MI and tumor grade but no relationship was found between COX-2, proliferation markers and MI, tumor grade and tumor size.
CONCLUSION： COX-2 is expressed in most GISTs and it may play an important role in the proliferation and progression of these tumors or a useful marker to identify GIST. Although immunohistochemical assessment of p53 can be used for distinguishing the risk groups of GISTs, tumor size and mitotic rate should be considered at the same time.     

Immunohistochemical analysis of molecular biological factors in intraductal papillary-mucinous tumors and mucinous cystic tumors of the pancreas

Background: To investigate the malignancy and differentiation of intraductal papillary-mucinous tumors (IPMTs) and mucinous cystic tumors (MCTs) of the pancreas, clinicopathologic characteristics and immunohistochemical features were analyzed. Methods: The clinicopathologic characteristics and immunohistochemical features of 24 patients with IPMT and 8 with MCT who underwent pancreatic resections at our hospital were examined. Immunohistochemical features analyzed included expression of p53 protein, proliferating cell nuclear antigen, integrins, interleukin-1 receptor type I, and hormone-associated receptors, and the factors correlated with malignancy were identified by multiple logistic regression. Results: Among the IPMTs, there were 16 intraductal papillary adenomas, 5 intraductal papillary adenocarcinomas, and 3 moderate dysplasias. Among the MCTs, there were 6 mucinous cyst adenomas and 2 mucinous cyst adenocarcinomas. Multivariate analysis revealed that of the clinicopathologic characteristics, only the presence of mural nodules (odds ratio (OR) 7.12, P?=?0.044) was independently correlated with the malignancy of IPMTs, and that of the immunohistochemical features, only α[Formula: See Text] integrin subunit expression was independently correlated with malignancy of pancreatic mucinous tumors (OR 15.6, P?=?0.036), especially IPMTs (OR 35.7, P?=?0.012). Conclusion: These results indicate that α[Formula: See Text]-containing integrin expression can be a significant marker of malignancy in pancreatic mucinous tumors.     

Clinical relevance of p53 index and expression of proliferating cell nuclear antigen and Ki-67 in gastric cancer

The prognostic value of the immunohistochemical expression of p53 protein, proliferating-cell nuclear antigen (PCNA) and Ki-67 antigen was evaluated in a series of 116 stage I–II gastric cancer patients. The staining for p53 protein (staining frequency and intensity) in malignant cells was expressed as a p53 index. Similarly, the staining frequency and intensity for PCNA and Ki-67 were evaluated. The p53 index was independent of the stage and differentiation grade, but significantly related to DNA ploidy, S-phase fraction and mitotic activity. A high p53 index was a sign of inferior survival, compared to a low or intermediate index. p53-negative tumours were also associated with poor survival. In a multivariate analysis, only the depth of tumour infiltration and the presence of nodal metastases were independent prognostic factors in stage I–II gastric cancer. PCNA expression and Ki-67 antigen expression were not related to the stage, ploidy, proliferative activity or p53 expression, and they had no impact on survival. The results indicate that p53 protein expression may be of prognostic significance in gastric cancer, while PCNA and Ki-67 antigen expression have no predictive value. Received: 2 February 1998 / Accepted: 16 June 1998     

Mucinous cystic neoplasms of the pancreas: pathology and molecular genetics

Mucinous cystic neoplasm (MCN) of the pancreas is a distinct clinicopathological entity characterized by mucin-producing epithelial and cyst-forming neoplasm with “ovarian-type” stroma beneath the epithelial component. It is clearly distinguished from ductal adenocarcinoma and intraductal papillary mucinous neoplasm (IPMN). However, MCN can progress to infiltrating carcinoma, and frequently shows a similar histological pattern to ductal adenocarcinoma. Several genetic alterations such as K-ras oncogene mutation, and epigenetic alterations such as hypermethylation of p16 in the invasive component of MCN are also common with ductal adenocarcinoma. Furthermore, recent technologies, including a laser-assisted microdissection system for histological slides and global gene expression profilings using DNA microarrays, made possible to identify more information about molecular abnormalities of MCNs. It is important to diagnose the lesions before they progress to an invasive carcinoma. MCN is one of the precursors of invasive pancreatic carcinoma.     

The prognosis of intraductal papillary mucinous tumors of the pancreas

BACKGROUND/AIMS: Intraductal papillary mucinous tumors of the pancreas have been recognized as a distinct clinical entity. However, their biological behavior has not been clearly defined. The aim of this study was to examine the prognosis of this tumor, to clarify the biological behavior and determine the most appropriate treatment. METHODOLOGY: Correlations between prognosis of operated cases and histopathologic features were investigated. RESULTS: In 105 patients with characteristic clinical features of intraductal papillary mucinous tumors, the lesions were classified as hyperplasias in 21%, intraductal tumors in 48% and invasive carcinomas in 31%. Minimal invasion was apparent in 25%, lymph node metastasis in 21%, and fistula formation in 31% of the invasive lesions. Non-invasive and minimally invasive intraductal papillary mucinous tumors were essentially free from risk of tumor recurrence. Other invasive intraductal papillary mucinous tumors showed a significantly poor prognosis. CONCLUSIONS: Because of the variation in pathological characteristics, patient outcome and the possibility of differential diagnosis, the treatment might be recommended as follows: the case of hyperplasia can be followed-up with close surveillance. Non-invasive and minimally invasive intraductal papillary mucinous tumors should be operated with function-preserving minimal pancreatectomy. For patients with invasive intraductal papillary mucinous tumors evident with preoperative imaging modalities, radical operations with lymph node dissection might be needed.     

Clinicopathological and immunohistochemical analysis of malignant features in mucinous cystic tumors of the pancreas

BACKGROUND/AIMS: To investigate the malignancy of mucinous cystic tumors (MCTs) of the pancreas, we examined clinicopathological features and immunohistochemical findings of MCT. METHODOLOGY: We analyzed the expression of p53 protein, proliferating cell nuclear antigen, alpha6-integrin subunit, alpha5beta1-integrin, and interleukin-1 receptor type I in tumor specimens from eight patients with MCT. RESULTS: The tumors were classified as mucinous cyst adenoma (n=6) or mucinous cyst adenocarcinoma (n=2). The actuarial five-year survival rate was 83.3%. All in eight MCTs had 'ovarian-type' stroma in the cyst wall. The alpha6-integrin subunit and p53 protein were expressed in adenocarcinoma tissues of MCTs, and in two adenomas the alpha6-integrin subunit and p53 protein were also co-expressed. CONCLUSIONS: Our present results indicate that coexpression of the alpha6-integrin subunit and p53 protein should be appreciated as an indicator of malignancy in MCTs.