The Study Of Expression Of Transient Receptor Potential Channels And Cholinergic Muscarinic Acetylcholine Receptors On Human Gastrointestinal Stromal Tumors

Background and Objects:Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in gastrointestinal (GI) tract, with an annual incidence of 1.2-1.4/10 million. GIST tumourlets, combined with sporadic GISTs, or just found in GI tumor postoperative specimens, or incidentally found by autopsy, with a detection rate as high as 9.1-35%. GISTs are potentially malignant biological behavior tumors, originating from interstitial cells of Cajal (ICCs) or stem cells to ICCs differentiation. ICCs are special type of stromal cells through GI tract, regulating GI motility by pacing basic electrical rhythm and mediating transfer of neurotransmitter. The mechanism is based on pacing unit, which comprise inositol trisphosphate (IP3) mediated calcium library, mitochondria, and nonselective cationic channels (NSCC). Transient receptor potential channels (TRPC), as a type of NSCC, are considered as the key structures of pacing of ICCs. Cholinergic nerves play an important role in neural regulation of GI motility by releasing acetylcholine binding to cholinergic muscarinic acetylcholine receptors (CHRM) on ICCs, which causes contractions of smooth muscles. It is our purpose to detect the expression of TRPC/CHRM subtypes on human GISTs, analyze the correlations between TRPC/CHRM and their clinical pathological characteristics, and further study whether GISTs maintain the structures of pacing and mediating neurotransmitter transfer functions of ICCs during their occurrence and development processes, aiming at further studying the potential electrophysiological characteristics of human GISTs.Methods:40 GIST specimens with complete diagnosis were collected from our pathology department, with 19 males and 21 females, aging from 26 to 73, average age of 54.6, median age at 53.5 years old.40 cases were classified according to histological characteristics and the biological behaviors malignant potential grading.40 gastrointestinal leiomyomas were collected as control group, with 18 males and 22 females, aging from 22 to 69, average age of 56.7, median age at 54.5 years old. The expression of TRPC1/3 and CHRM2/3 were detected by immunohistochemical method on human GISTs, and the correlations were analyzed between them and their clinical pathological characteristics.Results:1.57.5% GISTs express TRPC1, statistically higher than the control group of gastrointestinal leiomyomas (P<0.05). The expression of TRPC1 in stomach GISTs group was statistically higher than other groups (P＜0.05). The expression of TRPC1 in spindle cell type of GISTs was statistically higher than other types (P<0.05). The expression of TRPC1 in extremely-low-risk and low-risk groups of GISTs were statistically significant higher than risk and high-risk groups (P<0.01).2.47.5% GISTs express TRPC3, statistically higher than the control group of gastrointestinal leiomyomas (P＜0.05). The expression of TRPC3 in stomach GISTs group was statistically higher than other groups (P＜0.05). The expression of TRPC3 in spindle cell type of GISTs was statistically higher than other types (P<0.05). The expression of TRPC3 in extremely-low-risk and low-risk groups of GISTs were statistically significant higher than risk and high-risk groups (P<0.01).3.22.5% GISTs express CHRM2, statistically lower than the control group of gastrointestinal leiomyomas (P<0.01). The expression of CHRM2 in extremely-low-risk and low-risk groups of GISTs were statistically significant higher than risk and high-risk groups (P<0.01).4.55.0% GISTs express CHRM3, but the difference between the control group was not statistically significant (P>0.05). The expression of CHRM3 in stomach GISTs group was statistically higher than other groups (P<0.05). The expression of CHRM3 in spindle cell type of GISTs was statistically higher than other types (P<0.05). The expression of CHRM3 in extremely-low-risk and low-risk groups of GISTs were statistically significant higher than risk and high-risk groups (P<0.01).ConcIusions:1. Human GISTs express TRPC1 and TRPC3 subtypes.2. Human GISTs express CHRM2 and CHRM3 subtypes. 3. With the biological behaviors malignant potential grading of GISTs increased, the expression level of TRPC1, TRPC3, CHRM2 and CHRM3 decreased.4. GISTs have maintained part of structures of ICCs for pacing and mediating neurotransmitter transfer functions in gastrointestinal motility.