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

Abstract

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.

Correlation between Laminin-5 γ₂ Chain and Epidermal Growth Factor Receptor Expression in Esophageal Squamous Cell Carcinomas

“…In most carcinomas, LN-5 γ 2 is expressed in the carcinoma cells at the epithelial-stromal interface in the invasive front [10,11,12,13,14,15,16, 34]. These observations suggest that LN-5 γ 2 has an important role in cancer cell adhesion to the stroma.…”

“…Recent immunohistochemical studies have revealed that the LN-5 γ 2 is strongly expressed in disseminating and infiltrating tumor cells at the invasive front of epithelial carcinomas, and its increased expression in tumor tissues is associated with a poor prognosis [10,14,15,16, 34]. Our results were similar to these observations, and moreover, overexpression of LN-5 γ 2 was shown to be correlated with lymphatic invasion, vascular invasion and the tumor growth pattern in esophageal SCC.…”

“…These properties of LN-5 suggest its possible roles in tumor invasion and metastasis [9]. Predominant expression of the laminin-5 γ 2 chain (LN-5 γ 2 ) has been reported in various invasive carcinomas, such as adenocarcinomas of the colon [10, 11], pancreas [12], stomach [9], lung [13], cholangiocarcinoma [14] and squamous cell carcinoma (SCC) of the lung [13], oral cavity [15] and esophagus [16]. In most carcinomas, LN-5 γ 2 was predominantly observed in the carcinoma cells in the epithelial-stromal interface of the invasive front.…”

Cytoplasmic and stromal expression of laminin γ 2 chain correlates with infiltrative invasion in ovarian mucinous neoplasms of gastro-intestinal type

“…In invasive intrahepatic cholangiocarcinoma, the stromal accumulation of laminin Á 2 were significantly correlated with tumor aggressive factors and poor prognosis (19). The stromal laminin Á 2 expression is thought to contribute to the tumor cell migration and invasion in a variety of carcinomas (18,19,34).…”

“…It is a major component of the basement membrane of various types of epithelial tissue and plays important roles in cell differentiation, adhesion, and migration (14,15 (16,17), gastric (18), intrahepatic cholangial (19), lung (20), breast (16), and pancreatic (21) adenocarcinomas, and head and neck (22), esophageal (23) and uterine cervical (16,17,24) squamous cell carcinomas and malignant melanomas (23). However, the relationship between laminin Á 2 chain expression and ovarian GI-type mucinous neoplasms, including mural nodules, has not been elucidated.…”