Co-Expression of KIT Receptor and Its Ligand Stem Cell Factor in Merkel Cell Carcinoma

Abstract

Background/Aims: KIT receptor has been implicated in the pathogenesis of cancer, either by mutation or autocrine activation. Merkel cell carcinoma (MCC) is a rare KIT-positive cutaneous tumor. We investigated the co-expression of KIT and its ligand stem cell factor (SCF) in MCC. Methods: Sixteen specimens from 13 MCC patients of various tumor stages were examined by immunohistochemistry for SCF, KIT, Ki67/MIB-1 and cleaved caspase 3 expression, and for apoptosis by TUNEL. Results: KIT was expressed in 13 of 16 tumors, and SCF in 15 of 16 specimens. Co-expression of KIT and SCF was detected in 12 of 16 tumors. KIT and SCF immunoreactivity scores were independent of tumor stage. Ki67/MIB-1 proliferation rates were high, whereas apoptosis rates were low, and did not depend on KIT or SCF expression. Conclusion: Co-expression of KIT and SCF in a high percentage of MCC tumors hints to an autocrine mechanism. KIT and SCF expression in primary tumors and in metastases suggests an early event in Merkel cell transformation.

KIT receptor activation by autocrine and paracrine stem cell factor stimulates growth of merkel cell carcinoma in vitro

“…The MCC‐1 cell line expressed both KIT and SCF, as previously described for Merkel cell carcinoma tumors (Kartha and Sundram, 2008; Krasagakis et al, 2009). Similar to the findings in gastrointestinal stromal tumors (Hirano et al, 2008), the membrane‐bound form of SCF was more abundantly expressed than the soluble in MCC‐1 cells.…”

“…Therefore, the possible mode of activation and the function of KIT in Merkel cell transformation remains subject for further investigation. Recently, co‐expression of KIT and its ligand stem cell factor (SCF) has been reported in Merkel cell carcinoma biopsies (Kartha and Sundram, 2008; Krasagakis et al, 2009) suggesting an autocrine, ligand‐dependent, activation of KIT in Merkel cell carcinoma. However, no functional studies have been reported up to now that provide evidence for activity of the autocrine loop in Merkel cell carcinoma.…”

Unremitting Cell Proliferation in the Secretory Phase of Eutopic Endometriosis: Involvement of pAkt and pGSK3β

“…Expression of Ki67 is dependent on estrogens and is also linked to SCF/c-kit in other tissues and some cancers. 34,35 Increased cell proliferation has been related to a reduction in cell death and an increase in cell proliferation due to abundance of c-myc, 5 although a differential regulation of micro-RNAs in the secretory and proliferative phase of the cycle, which is under hormonal control, 36 has also been considered.…”

Merkel Cell Carcinoma: A Retrospective Study on 48 Cases and Review of Literature

“…About chemotherapy, its role should be revisited with newer molecules including targeted agents. In this way, coexpression of KIT in a high percentage of MCC suggests an important role in Merkel cell transformation [80], so that the potential use of KIT kinase inhibitor-based therapies, as imatinib, should be also considered in metastatic MCC [81, 82]. …”