Immunohistochemical expression of receptor-tyrosine kinase c-kit protein in invasive ductal carcinoma of the pancreas

Abstract

The expression of receptor tyrosine kinase c-kit and its biologic significance in pancreatic cancer are unclear. We studied the expression of c-kit protein (c-KIT) in resectable invasive ductal carcinomas (IDCs) of the pancreas, in order to assess whether a selective c-kit inhibitor, STI571 (Glivec), may be applied for the treatment of pancreatic IDCs. This study included 72 pancreatic IDC patients who received a pancreatectomy between 1982 and 2002. The expression of c-KIT was analyzed retrospectively by immunohistochemistry. c-KIT was expressed in 78% (56/72) of the pancreatic IDCs. c-KIT expression did not correlate with any clinicopathological factor of pancreatic IDC and c-KIT expression had no significant influence on the survival of the patients. The survival rate of the adjuvant chemotherapy (ACT) (+) group was significantly higher than that of the ACT (-) group, but c-KIT expression had no significant effects on the efficacy of the ACT. Multivariate analysis indicated that the pTNM stage, grade and ACT were all significant variables for survival in IDCs overall. As c-KIT was expressed in 78% of the pancreatic IDCs, it suggests that STI571 may be a beneficial agent for chemotherapy against human pancreatic IDCs.

Tissue Biomarkers for Prognosis in Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-analysis

“…Twenty-four studies reported on HER-2 data; however, only 1 was eligible for this review (72). Other underrepresented signal transduction components include 13 studies reporting for epidermal growth factor receptor (131)(132)(133), c-kit (134)(135)(136), PTEN (137), and c-myc (138)(139)(140). The Wnt signaling pathway, important in embryogenesis and gastrointestinal cancer development, was underrepresented with even b-catenin, investigated in 7 studies having no representation.…”

Abnormal expression of Endoglin and its receptor complex (TGF-β1 and TGF-β receptor II) as early angiogenic switch indicator in premalignant lesions of the colon mucosa

“…Moreover, whereas TGF-ß1 in situ expression was significantly higher only in high dysplastic polyps, a progressive increase in TGF-ß1 transcript and protein accumulation was observed in successive stages of the colorectal tumor progression. TGF-ß1 has been found to be overexpressed locally in various types of solid tumors, including cancer of the breast (70), colon (71,72), esophagus (73), stomach (74), pancreas (75), liver (76), lung (77), prostate (78), brain (79), and malignant melanoma (80). Overexpression is frequently correlated with advanced tumor stage, metastases and a poorer overall prognosis.…”

A distinct expression pattern and point mutation of c-kit in papillary renal cell carcinomas

“…7 KIT is not only expressed in tumors derived from these cell lineages, but also in other malignancies such as small cell lung cancer, pancreatic ductal carcinoma, angiomyolipoma, and chromophobe renal cell carcinoma. 5,[8][9][10] Gain-of-function mutations of the c-kit gene are known in mast cell neoplasia and gastrointestinal stromal tumors. 11,12 The oncogenic mutations of c-kit gene or activation of KIT lead to activation of signal transduction cascades, which regulates cell proliferation, apoptosis, chemotaxis, and adhesion.…”