Expression of Laminin-5-γ-2 Chain in Intraductal Papillary-Mucinous and Invasive Ductal Tumors of the Pancreas

Fukushima, Noriyoshi; Sakamoto, Michiie; Hirohashi, Setsuo

doi:10.1038/modpathol.3880326

Cited by 21 publications

(13 citation statements)

References 13 publications

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“…MMP-26 expression had a trend to increase from T1 to T4, and this protease was significantly more often expressed in tumors having metastatic lymph nodes. Furthermore, MMP-26 often colocalized with cells positive for laminin-5, an indicator of invasiveness of pancreatic tumor cells, 48 thus linking this protease to aggressive behavior of pancreatic adenocarcinomas. However, a higher number of tumors would be required to definitely conclude whether MMP-26 could serve as a marker of metastasis in pancreatic cancer.…”

Section: Discussionmentioning

confidence: 99%

Increased expression of matrix metalloproteinases-21 and -26 and TIMP-4 in pancreatic adenocarcinoma

et al. 2007

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Pancreatic adenocarcinoma is known for early aggressive local invasion, high metastatic potential, and a low 5-year survival rate. Matrix metalloproteinases (MMPs) play important roles in tumor growth and invasion. Earlier studies on pancreatic cancer have found increased expression of certain MMPs to correlate with poorer prognosis, short survival time or presence of metastases. We studied the expression of MMP-21, -26, and tissue inhibitor of matrix metalloproteinases ( Keywords: matrix metalloproteinase; adenocarcinoma; tissue inhibitor of metalloproteinase Pancreatic cancer is one of the most lethal types of cancer: the 5-year survival rate of pancreatic adenocarcinoma is under 5%.1,2 Other types of pancreatic tumors (15% of all tumors) include insulinoma, gastrinoma, and carcinoid tumor. Pancreatic cancer is notorious for its late clinical presentation, early and aggressive local invasion, and metastatic potential.3 The diagnosis is confirmed using ultrasound combined with biopsy as well as computed tomography, and tumor markers such as CA 19-9. If metastases are not found, the Whipple operation (pancreaticoduodenectomy) is performed to remove the tumor. If metastases are detected, palliative treatments are chosen, such as biliary bypass procedure or chemo/radiotherapy. A known risk factor for pancreatic cancer is smoking, which increases the risk two-to three-fold. 4 Also, patients with chronic pancreatitis have increased risk for developing pancreatic carcinoma. 5,6

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Section: Discussionmentioning

confidence: 99%

Increased expression of matrix metalloproteinases-21 and -26 and TIMP-4 in pancreatic adenocarcinoma

et al. 2007

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“…There is therefore a potential for misdiagnosing IPMC or IC-IPMC as MI-IPMC. Recently, other researchers have reported laminin-5-γ-2 or periostin as a useful marker for detecting invasive tumor cells in IPMNs, which might be associated with cancer-cell invasiveness (7,8). Pericellular proteolysis is crucial in tumor cell invasion.…”

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confidence: 99%

Stromal thrombospondin-1 expression is a prognostic indicator and a new marker of invasiveness in intraductal papillary-mucinous neoplasm of the pancreas

et al. 2010

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The invasion of intraductal papillary-mucinous neoplasm (IPMN) is sometimes difficult to diagnose using only ordinary hematoxylin-eosin sections. The aim of this study was to evaluate the invasion of IPMN more precisely using thrombospondin-1 (TSP1) immunohistochemistry as a useful adjunct to morphological examination. Eighty patients that underwent primary resection for pancreatic IPMNs were retrospectively analyzed. The 80 IPMNs were studied for the expression of TSP1, MUC1-CORE, MUC2, and MUC5AC. The cases were evaluated for dysplasia, the presence of invasion, hisological subtypes, and survival. The 80 IPMNs were classified into 29 intraductal papillary-mucinous adenomas (IPMAs), 10 borderline IPMNs, 18 noninvasive intraductal papillary-mucinous carcinomas (IPMCs), and 23 invasive IPMCs according to the WHO classification. Invasive IPMCs were further divided into 12 minimally invasive IPMCs (MI-IPMCs) and 11 invasive carcinomas originating from IPMCs (IC-IPMCs) according to the Japan Pancreatic Society classification. The rate of strongly positive cases with more than 30% of the cancer stroma area expressing TSP1 was significantly higher in MI-IPMC and IC-IPMC than in noninvasive IPMC (P = 0.035, 0.005). Furthermore, patients in the strongly positive group had a significantly poorer prognosis compared to patients in the negative-weakly positive group (P = 0.008, log-rank test). Of the 80 tumors, 22 were classified into gastric-, 45 into intestinal-, 7 into pancreatobiliary-, and 6 into oncocytic-type IPMNs according to criteria described previously. The cases with a strongly positive expression of TSP1 were frequently detected in the pancreatobiliary and oncocytic types (P = 0.001). In conclusion, stromal TSP1 expression is a prognostic indicator and a new marker of invasiveness in IPMN.Intraductal papillary-mucinous neoplasms of the pancreas (IPMNs) are a well-characterized group of intraductal, mucin-producing, cystic neoplasms of the pancreas with a clear malignant potential (1, 2). A half of surgically resected IPMNs are intraductal papillary-mucinous adenoma (IPMA) or borderline IPMN even under current international criteria (21), and it is still unclear when they change to noninvasive intraductal papillary-mucinous carcinoma (IPMC), how long IPMC retains a status of "carcinoma in situ", and when IPMC achieves invasiveness. Particularly, invasive carcinoma originating from intraductal papillary-mucinous carcinoma (IC-IPMC) showed similar malignant behavior compared with conventional invasive ductal carcinoma both clinically and histologically (15). Minimally invasive IPMC (MI-IPMC) has been categorized within the classification of pancreatic carcinoma used by

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“…It has been shown that laminin gamma 2 chain expression in the in situ component of intraductal papillarymucinous tumors (IPMTs) of the pancreas tends to increase with tumor development. 15 The expression of intraductal components in both intraductal growth type of intrahepatic cholangiocarcinoma and IPMT had a similar pattern, which suggests that the cytoplasmic expression of carcinoma cells for laminin gamma 2 chain plays an important role in the progression from noninvasive intraductal tumor to an invasive tumor. Tumor invasion is the basic indicator for progression from premalignant to malignant tumors.…”

Section: Discussionmentioning

confidence: 88%

“…Other studies showed that the non-neoplastic tissue, including pancreatic duct, colonic mucosa and mammary duct, fails to demonstrate laminin gamma 2 by immunohistochemical approach and in situ hybridization. 8,15,16 Soini et al 16 suggested that the concentration of laminin gamma 2 in non-neoplastic duct is so low that it cannot be detected by immunohistochemistry.…”

Section: Discussionmentioning

confidence: 99%

“…6 Laminin gamma 2 chain plays a key role in cell migration during tumor invasion. Overexpression of laminin gamma 2 chain has been particularly demonstrated at the invasive front of various carcinomas, including colorectal, [7][8][9][10][11] gastric, 12 lung 13,14 and pancreatic [15][16][17] adenocarcinomas, and head and neck, 18 tongue 19 and esophageal 20 squamous cell carcinomas. The prognostic indicator of its expression has been reported in several tumors.…”

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Aberrant expression of laminin gamma 2 chain and its prognostic significance in intrahepatic cholangiocarcinoma according to growth morphology

et al. 2004

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Laminin gamma 2 chain is an extracellular matrix protein that plays an important role in cell migration and tumor invasion. We report altered expression and characteristic localization of this chain in a series of 105 cases of intrahepatic cholangiocarcinomas examined immunohistochemically. All tumors were grossly classified into the following three types: intraductal growth type (n ¼ 9), periductal infiltrating type (n ¼ 8) and mass-forming type (n ¼ 88). The tumors exhibited three distinct staining types: basement membrane staining, cytoplasmic staining and stromal staining. The basement membranous staining of laminin gamma 2 chain was more frequent in biliary dysplasia, intraductal growth and periductal infiltrating type than in mass-forming type. The cytoplasmic staining of carcinoma cells was observed especially at the cancer-stromal interface or at the invasive front of tumors. Stromal staining of laminin gamma 2 chain was essentially localized in the stroma around cancer cells at the invasive area, and the expression was significantly correlated with tumor aggressive factors and a poor prognosis in patients with intrahepatic cholangiocarcinoma. We conclude that laminin gamma 2 chain exhibits aberrant expression in a stepwise manner through different aggressive stages of tumor progression.

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Expression of Laminin-5-γ-2 Chain in Intraductal Papillary-Mucinous and Invasive Ductal Tumors of the Pancreas

Cited by 21 publications

References 13 publications

Increased expression of matrix metalloproteinases-21 and -26 and TIMP-4 in pancreatic adenocarcinoma

Increased expression of matrix metalloproteinases-21 and -26 and TIMP-4 in pancreatic adenocarcinoma

Stromal thrombospondin-1 expression is a prognostic indicator and a new marker of invasiveness in intraductal papillary-mucinous neoplasm of the pancreas

Aberrant expression of laminin gamma 2 chain and its prognostic significance in intrahepatic cholangiocarcinoma according to growth morphology

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