Clinical and prognostic significances of nuclear and cytoplasmic KIT expressions in extrahepatic bile duct carcinomas

Abstract

After receiving FDA approval as a therapeutic regimen in gastrointestinal stromal tumors, the tyrosine kinase inhibitor imatinib mesylate has been applied to the treatment of other solid malignant neoplasms. To evaluate the usefulness of imatinib mesylate as a possible therapeutic regimen in extrahepatic bile duct carcinomas, an immunohistochemical study for KIT was performed in 289 cases of extrahepatic bile duct carcinomas, and mutational analysis of exon 11 of the c-kit gene was performed in 20 cases that were arbitrarily retrieved from the cases with KIT expression. Cytoplasmic KIT expression was observed in 54 cases (19%) and nuclear KIT in 58 cases (20%) of extrahepatic bile duct carcinoma. Nuclear KIT expression was more frequent in cases with vascular invasion (Po0.001), whereas cytoplasmic KIT expression was more common in tumors of T1-T3 than in those of T4 (P ¼ 0.04), and was more frequently observed in cases with a papillary growth pattern (P ¼ 0.03). Patients with cytoplasmic KIT-positive tumors had significantly better survival both by univariate (P ¼ 0.01) and multivariate analyses (P ¼ 0.04). Infrequent cytoplasmic KIT expression without mutation of exon 11 suggests that imatinib mesylate may not be effective for the treatment of extrahepatic bile duct carcinoma. However, immunohistochemical study for KIT may be helpful in routine pathologic examinations for evaluating better prognosis for patients with extrahepatic bile duct carcinoma. In addition, more frequent nuclear expression of KIT in cases with vascular invasion suggests that nuclear KIT expression may contribute to the progression of extrahepatic bile duct carcinoma.

Overexpression of EGFR and absence of C‐KIT expression correlate with poor prognosis in salivary gland carcinomas

“…Similar observations have been reported in small cell lung cancer by Rohr et al. , 41 in extrahepatic bile duct carcinoma 42 and breast cancer 40 . Rohr et al.…”

Decreased expression of focal adhesion kinase is associated with a poor prognosis in extrahepatic bile duct carcinoma

“…Previous studies have shown some prognostic factors, such as resection margin [23], lymph node metastasis [24], and pancreatic parenchymal invasion [25]. Furthermore, some molecules, including KIT [26], epidermal growth factor receptor (EGFR) [27], Caveolin-I [28], and MUC4 [29], were revealed to be prognostic factors of EBD carcinomas, but FAK expression in EBD carcinomas has not been evaluated.…”

Comparison of tumor markers for predicting outcomes after resection of nonfunctioning pancreatic neuroendocrine tumors

“…c-KIT has been found as a marker of poor prognosis and decreased survival in a variety of malignjancies. 17,18 We further assessed whether the 4 patients with c-KITÀpositive tumors had poor outcome. Two of these patients had disease-specific death, whereas the other 2 were alive with no distant metastasis.…”