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.     

Efficacy of peroral pancreatoscopy in the diagnosis of pancreatic diseases

BACKGROUND: The aim of this study was to evaluate the usefulness of peroral pancreatoscopy in the diagnosis of pancreatic diseases. METHODS: Both 3.7-mm (thin) and 0.8-mm (ultra-thin) diameter fiberoptic pancreatoscopes were used in 115 cases (pancreatic cancer, 35; benign ductal stenosis, 20; intraductal papillary-mucinous tumor, 60). RESULTS: Observation rates for pancreatic cancer, benign ductal stenosis, and intraductal papillary-mucinous tumor were, respectively, 63%, 80%, and 95%. Tumor vessels and papillary tumor were observed when pancreatic cancer was smaller than 2 cm but not when the tumor was larger than 2 cm. Stenosis without significant mucosal changes was observed in 62% of cases of benign ductal stenosis. Coarse mucosa and friability were observed more frequently in association with pancreatic cancer than benign ductal stenosis. Granular mucosa or papillary tumor could be observed in 74% of cases of intraductal papillary-mucinous tumor. Papillary tumor was observed with increasing frequency in cases of intraductal papillary-mucinous tumor as the degree of malignancy increased. CONCLUSIONS: Peroral pancreatoscopy with an ultra-thin fiberscope is useful in the diagnosis of minute pancreatic lesions. Peroral pancreatoscopy with a thin fiberscope can provide a definitive diagnosis of intraductal papillary-mucinous tumor including the degree of malignancy.     

Immunohistochemical analysis of cyclooxygenase-2 expression in pancreatic tumors

Summary Background A considerable amount of evidence collected from several experimental systems and clinical studies with nonsteroidal Anti-inflammatory drugs (NSAIDs) indicates that Cox-2 may play a major role in colorectal tumorigenesis, but little information about Cox-2 expression in pancreatic tumors is available. In this study, we investigated Cox-2 expression by means of both immunohistochemical analysis and immunoblot analysis in pancreatic tumors. Methods Fifty invasive ductal adenocarcinomas and 26 intraductal papillary-mucinous tumors (IPMTs) were used for immunohistochemical analysis, and five pancreatic cancer tissues and five pancreatic cancer cell lines for immunoblot analysis. Results Cox-2 was expressed in 72% of the invasive ductal adenocarcinomas, 31% of intraductal papillary-mucinous adenocarcinomas, and none of intraductal papillary-mucinous adenomas. The expression rate of Cox-2 in intraductal papillary-mucinous adenocarcinomas was significantly higher than that in intraductal papillary-mucinous adenomas, and that in invasive ductal adenocarcinomas was significantly higher than that in intraductal papillary-mucinous carcinomas. However, there was no significant correlation between Cox-2 expression and the prognosis and clinicopathological factors. Immunoblot analysis identified Cox-2 in all of pancreatic cancer tissues and 60% of cell lines. Conclusion The biological role of cyclooxygenase-2 (Cox-2) in carcinoma cells should be investigated with reference to the cancer progression of the pancreas.     

Immunohistochemical analysis of cyclooxygenase-2 expression in pancreatic tumors.

BACKGROUND: A considerable amount of evidence collected from several experimental systems and clinical studies with nonsteroidal Anti-inflammatory drugs (NSAIDs) indicates that Cox-2 may play a major role in colorectal tumorigenesis, but little information about Cox-2 expression in pancreatic tumors is available. In this study, we investigated Cox-2 expression by means of both immunohistochemical analysis and immunoblot analysis in pancreatic tumors. METHODS: Fifty invasive ductal adenocarcinomas and 26 intraductal papillary-mucinous tumors (IPMTs) were used for immunohistochemical analysis, and five pancreatic cancer tissues and five pancreatic cancer cell lines for immunoblot analysis. RESULTS: Cox-2 was expressed in 72% of the invasive ductal adenocarcinomas, 31% of intraductal papillary-mucinous adenocarcinomas, and none of intraductal papillary-mucinous adenomas. The expression rate of Cox-2 in intraductal papillary-mucinous adenocarcinomas was significantly higher than that in intraductal papillary-mucinous adenomas, and that in invasive ductal adenocarcinomas was significantly higher than that in intraductal papillary-mucinous carcinomas. However, there was no significant correlation between Cox-2 expression and the prognosis and clinicopathological factors. Immunoblot analysis identified Cox-2 in all of pancreatic cancer tissues and 60% of cell lines. CONCLUSION: The biological role of cyclooxygenase-2 (Cox-2) in carcinoma cells should be investigated with reference to the cancer progression of the pancreas.     

Smallest cystic tumor, measuring 5 mm, was identified as an invasive adenocarcinoma among multiple intraductal papillary-mucinous tumors

We encountered a case of four cysts of intraductal papillary-mucinous tumor in the pancreas, a 25-mm diameter tumor, a 20-mm tumor, and a 10-mm tumor in the pancreatic body and tail, and a 5-mm diameter tumor in the uncinatus process, and the smallest diameter intraductal papillary-mucinous tumor (5 mm) was regarded as an invasive papillary adenocarcinoma, while the other three intraductal papillary-mucinous tumors were adenomas. A 63-year-old asymptomatic male was indicated of the presence of multiple pancreatic tumors by computed tomography during a physical examination. Endoscopic retrograde cholangiopancreatography revealed three cysts (25 mm, 20 mm, 10 mm diameter tumor) in the pancreatic body and tail, and one cyst 5 mm) in the uncinatus process. Cytologic examination of the pancreatic juice determined them as Class V. Based on a diagnosis of malignant intraductal papillary-mucinous tumors, he underwent distal pancreatectomy with removal of the uncinatus process. Pathologically, three cysts in the body and tail of the pancreas were found to be adenomas, but the 5-mm cyst in the uncinatus process was found to be an invasive intraductal papillary-mucinous tumor. The interstitium had been invaded by cancer, and the uncinatus process was the cancer positive surgical margin, and cystological examination of the pancreatic juice through repeated endoscopic retrograde cholangiopancreatography resulted in a class V, so the patient underwent a total pancreatectomy. When diagnosing intraductal papillary-mucinous tumor(s), there is the possibility of incorrectly differentiating between benignancy and malignancy when the diagnosis is based on cyst diameter, as is conventional.     

p53 protein expression in intraductal papillary mucinous tumors (IPMT) of the pancreas as an indicator of tumor malignancy

BACKGROUND/AIMS: Intraductal papillary mucinous tumors, as a cystic disease in the pancreas, clinically has a more indolent and favorable course than invasive ductal pancreas carcinoma. However, some cases of intraductal papillary mucinous tumors show invasive and rapid progression like ductal pancreas carcinoma and the prognosis of such patients is sometimes poor. In the current study, we carried out immunohistochemical staining of intraductal papillary mucinous tumor tissues for p53 and investigated whether positive staining indicates tumor malignancies and has a prognostic value for intraductal papillary mucinous tumors. METHODOLOGY: Nineteen (19) patients who underwent pancreatic resection under the diagnosis of intraductal papillary mucinous tumors at the Chiba University Hospital between April 1992 and December 1996 were studied. We performed immunohistochemical staining of p53 as well as of PCNA, Ki-67 and Bcl-2 using their respective antibodies. Pathological findings revealed that 9 cases were intraductal papillary adenoma, 9 were intraductal papillary adenocarcinoma, and one was invasive ductal papillary adenocarcinoma. RESULTS: p53 expression could only be detected in the 1 case with invasive ductal papillary adenocarcinoma. Significant association could not be found between histological features and immunohistochemical staining of PCNA, Ki-67 and Bcl-2. CONCLUSIONS: p53 protein expression could be detected after progression to invasive type of intraductal papillary mucinous tumors. The present results demonstrate that p53 expression might be an indicator of invasive progression in intraductal papillary mucinous tumors, and might represent a surgical indicator of intraductal papillary mucinous tumors.     

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.     

Intraductal papillary-mucinous tumors of the pancreas

BACKGROUND/AIMS: To elucidate the risk of malignancy and the morphological alterations associated with malignancy. METHODOLOGY: Thirty cases of intraductal papillary-mucinous tumors and 5 papillary-mucinous carcinomas (invasive intraductal papillary-mucinous tumors) of the pancreas were clinicopathologically and histopathologically analyzed. RESULTS: The invasive carcinoma developed on the basis of severe dysplasia-carcinoma in situ changes and never from mild or moderate dysplasia changes. However, tumor cell projections of intraductal papillary-mucinous tumors encroached into the duct wall and/or the stroma introduced just beneath the epithelium and "intraductal" tumor cells sometimes came in direct contact with the "extraductal" connective tissues even in adenomas. The frankly invasive adenocarcinoma components of invasive intraductal papillary-mucinous tumors were characterized by the lack or poor formation of their own basement membrane and were usually surrounded by the extensive collagenous proliferation, desmoplastic reaction. Such stromal alterations never developed around the "extraductal" components of non-invasive intraductal papillary-mucinous tumors. CONCLUSIONS: The risk of malignancy for an individual intraductal papillary-mucinous tumor was increased with the degree of cellular and/or structural atypia. The desmoplastic reaction with poor formation of the basement membrane is the sine qua non of the "true invasion".     

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.     

A case of mixed adenoneuroendocrine carcinoma of the pancreas mimicking intraductal papillary mucinous carcinoma

A previously healthy 52-year-old man was referred to our hospital for further evaluation of main pancreatic duct dilatation. The preoperative work-up was consistent with intraductal papillary mucinous carcinoma (IPMC) derived from a mixed type intraductal papillary mucinous neoplasm (IPMN), because multilocular cysts with enhancing thickened pancreatic head walls and dilated pancreatic ducts lined with dysplastic mucinous epithelium, with papillary proliferation from the pancreatic body to the tail, were observed; in addition, the pancreatic juice cytology was class V, which is suggestive of adenocarcinoma. Total pancreatectomy was performed because a definite mass was not found before surgical resection and the tumors could have spread to the tail. The pathological diagnosis was mixed adenoneuroendocrine carcinoma of the pancreatic head. IPMN with high- or low-grade dysplasia was not observed anywhere in the pancreatic duct. The pancreatic ductal adenocarcinoma consisted of large caliber malignant glands with intraluminal flat or papillary structures; therefore, we were unable to recognize a definite pancreatic mass before surgical resection, and suspected an IPMC derived from a mixed type IPMN.     

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.     

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.     

Invasive ductal adenocarcinoma of the pancreas may originate from the larger pancreatic duct: a study of 13 tumors less than 2 cm in diameter

Background/Purpose

We aimed to elucidate the origin/primary site of invasive ductal adenocarcinoma of the pancreas, based on the distribution of intraductal carcinoma components. These components were identified by a mural elastic fiber cuff.

Methods

Thirteen specimens from patients with invasive ductal adenocarcinoma (microscopically, less than 2?cm in diameter) of the pancreas were studied histopathologically. Variants of invasive ductal adenocarcinoma and intraductal papillary-mucinous carcinoma were excluded.

Results

Intraductal carcinoma components of invasive ductal adenocarcinoma were found in 12 of the specimens 13 (92%), and were observed within the tumor mass and/or on its boundary, or outside the tumor mass. Intraductal components were characterized by low papillary projections lacking a fibrovascular core, with/without surrounding tubular structures, or by irregular stratification and pleomorphism of the epithelial cells. Invasive components mostly showed a tubular pattern with desmoplasia. The distribution of the intraductal components in the 12 specimens was as follows: in 9 (75%), they were in both the main pancreatic duct and large branch ducts; and in 3, they were in the smaller branch ducts only.

Conclusions

Invasive ductal adenocarcinomas of the pancreas may originate most frequently from the main pancreatic duct or larger branch ducts, while the smaller ducts are less often the site of cancer origin.

     

Intraductal papillary-mucinous tumors of the pancreas: Clinicopathologic features, outcome, and nomenclature. Members of the Pancreas Clinic, and Pancreatic Surgeons of Mayo Clinic

BACKGROUND & AIMS: Intraductal papillary-mucinous tumor (IPMT) of the pancreatic ducts is increasingly recognized. This study investigated if clinical, imaging, or, histological features predicated outcome, formulated a treatment algorithm, and clarified relationships among IPMT, mucinous cystic neoplasms of the pancreas (MCN), and chronic pancreatitis. METHODS: The medical records, radiographs, and pathological specimens of 15 patients with IPMT (dilated main pancreatic duct or branch ducts with mucin overproduction) who were evaluated between October 1983 and January 1994 were reviewed. RESULTS: One patient had hepatic metastases. Fourteen underwent an operation (6 distal pancreatectomy, 4 total pancreatectomy, and 4 pancreaticoduodenectomy); all had dysplastic intraductal epithelium and chronic pancreatitis, whereas 3 had invasive adenocarcinoma. After a median of 25 months, 10 patients were alive; 3 of 4 with malignant and 2 of 11 with benign IPMT died (P < 0.05). Patients with or without carcinoma had similar clinical and radiographic features. A clinical diagnosis of chronic pancreatitis had been made in 9 patients with benign IMPT and in none with malignant IPMT (P < 0.05). CONCLUSIONS: IPMT is a dysplastic and likely precancerous lesion that is frequently diagnosed as chronic pancreatitis and is separate from MCN. Because it is not possible to distinguish noninvasive from invasive IPMT preoperatively, complete surgical excision of the dysplastic process is our treatment of choice whenever appropriate. (Gastroenterology 1996 Jun;110(6):1909-18)     

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.     

Long-term survival after surgical resection for pancreatic cancer

BACKGROUND/AIMS: Pancreatic cancer remains one of the most formidable tumors defying early detection and effective treatment. Long-term survivors, however, do exist after resection. We investigated the clinicopathologic features of patients with pancreatic cancer who survived more than 5 years to draw out some suggestions concerning the indication of surgical treatment. METHODOLOGY: We studied the clinicopathologic features of 13 patients with pancreatic cancer who survived more than 5 years after resection. We reviewed their clinical records to investigate preoperative symptoms, serum tumor markers, operative findings, postoperative adjuvant therapy, and modes of recurrence and survival periods. Information on the location, size, histology and spread of the primary tumors were mainly obtained from pathology reports. RESULTS: Histologic types of the long survivors included ductal adenocarcinoma of common type in 4 patients, mucinous noncystic adenocarcinoma in 2, intraductal papillary-mucinous carcinoma (invasive) in 4, undifferentiated carcinoma in 1, endocrine tumor (islet cell carcinoma) in 1 and acinar cell carcinoma in 1. All 4 cases of ductal adenocarcinoma of the common type showed a moderate invasion either to the retroperitoneum, the portal vein or the duodenum. Two patients with mucinous noncystic carcinoma attained a long survival despite extensive invasion of the pancreatic stroma, although one died of peritoneal carcinomatosis. Two of 4 patients with intraductal papillary-mucinous cancer (invasive) died of peritoneal dissemination 6 and 11 years after resection, respectively. Three patients with cancer of other special histologic types, i.e., undifferentiated, well-differentiated endocrine carcinoma and acinar cell carcinoma, showed invasion of the portal vein and splenic artery, involvement of the retroperitoneum and a metastatic tumor in the liver, respectively. CONCLUSIONS: Whereas special histologic types including ductal variants tended to predispose to long-term survival, ductal adenocarcinoma of the common type had some chance of long survival even with invasion of the surrounding tissues.     

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.     

Ductal branch-oriented minimal pancreatectomy: Two cases of successful treatment

Two patients with intraductal papillary-mucinous adenoma of the pancreas were successfully treated by ductal branch-oriented minimal pancreatectomy. We propose this novel less invasive ductal branch-oriented pancreatectomy, as indicated for benign ductal ectasia of the pancreas. The cystically dilated branch duct is identified by intraoperative ultrasonography, intraoperative balloon pancreatography, and injection of indigocarmine into the cyst. The cystically dilated branch is resected from the surrounding pancreas together with minimal removal of the pancreatic parenchyma. The communicating duct and cutting margins are tightly ligated to prevent pancreatic juice leakage and fistula. A drainage tube is placed in the main pancreatic duct whenever possible. Histopathologic examination of the transected branch duct is necessary to check for mucosal extension of dysplastic epithelium. This ductal branch-oriented minimal pancreatectomy is the least invasive pancreatectomy and a suitable operation for branch-type ductal ectasia of the pancreas, which is usually benign.     

Update on the Molecular Pathogenesis of Pancreatic Tumors Other than Common Ductal Adenocarcinoma

Purpose: Although ductal adenocarcinoma is the most common and well known pancreatic tumor type, other distinct epithelial neoplasms affecting the pancreas that show different symptoms, biological behaviors and outcomes are becoming more frequently recognized and documented. Pancreatic epithelial tumors may be separated into ductal and nonductal neoplasms. The former group includes pancreatic ductal adenocarcinoma, intraductal papillary-mucinous tumor, mucinous cystic tumor and serous cystic tumor. The latter group includes pancreatic endocrine tumor, pancreatic acinar cell carcinoma, pancreatoblastoma and solid-pseudopapillary tumor. The aim of this review is to summarize recently acquired knowledge regarding the molecular characterization of these uncommon pancreatic epithelial neoplasms. Recent Findings: Molecular studies of uncommon pancreatic epithelial tumors suggest that the different morphological entities are associated with distinct molecular profiles, highlighting the involvement of different molecular pathways leading to the development of each subtype of pancreatic neoplasm. Conclusion: The correct classification of rare pancreatic epithelial tumors and the identification of their characteristic molecular aspects is the fundamental starting point in identifying novel diagnostic molecular tools and new targets for innovative therapeutic Strategies.     

c-erbB-2 、bcl-2和p53在结直肠肿瘤中的表达及其临床意义

背景：c-erbB-2、bcl-2和突变型p53在结直肠腺瘤癌变过程中相互调节并发挥重要作用。目的：探讨结直肠肿瘤中c-erbB-2、bcl-2和D53蛋白的表达及其临床意义。方法：取42例结直肠腺癌、10例腺瘤和10例正常结直肠黏膜组织，以免疫组化方法检测其中c-erbB-2、bcl-2和p53蛋白的表达，分析其表达与腺癌临床病理特征的关系。结果：c-erbB-2、bcl-2和p53蛋白在腺癌、腺瘤和正常黏膜组织中的表达差异均有统计学意义（P〈0．05），bcl-2蛋白在腺癌组织中的表达低于腺瘤组织，c-erbB-2和p53蛋白在腺癌组织中的表达高于腺瘤和正常黏膜组织。c-erbB-2蛋白的表达随腺癌分化程度的降低而增高，bcl-2蛋白的表达随腺癌分化程度的降低而降低：c-erbB-2和p53蛋白的表达与淋巴结转移和Dukes分期呈正相关。腺癌组织中bcl-2与p53蛋白的表达呈负相关（rs=-0．301，P〈0．05）。结论：c-erbB-2与结直肠癌的进展、分化和转移相关。腺癌组织中p53高表达和bcl-2相对低表达提示两者可能参与了结直肠癌的发生、发展过程，bcl-2过表达可能在结直肠癌发生的早期起作用。