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Technical Briefs |
1
Medical Laboratory and
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Medical Research, and
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Section of Gastroenterology, Taichung Veterans General Hospital, Taichung, 407, Taiwan;
4
Department of Surgery, Cheng-Ching Hospital, Taichung, 407, Taiwan;
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Department of Internal Medicine, Kuan-Teng General Hospital, Taichung, 433, Taiwan;
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School of Medical Technology, Chung-Shan Medical & Dental College, Taichung, 402, Taiwan;
a author for correspondence: fax 886-4-359-2705, e-mail c1035{at}vghtc.vghtc.gov.tw
Serotonin [5-hydroxytryptamine (5-HT)] is involved in physiological functions such as sleep, hemostasis, and behavior regulation, and in pathological conditions such as carcinoid syndrome, thrombosis, and cardiovascular diseases (1)(2). Plasma 5-HT is derived largely from the enteroendocrine cell in the gastrointestinal tract. The evidence of the relationships between 5-HT and these pathological conditions has been obtained mostly from studies of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the plasma of humans (3). The most reliable laboratory test to detect a carcinoid tumor is the repeated determination of the urinary 5-HIAA (4). In addition, whole- blood 5-HT is increased in patients with metastatic midgut carcinoid tumors (1)(2).
Liquid chromatography with electrochemical detection provides the highest sensitivity for the determination of human plasma 5-HT and/or 5-HIAA. However, widely variable "normal" concentrations of plasma 5-HT (0.5–44 µg/L) have been reported (5)(6)(7)(8)(9)(10). These inconsistencies might be attributable to variations in assay techniques or calibration or the release of 5-HT from platelets during sample preparation. In our previous study, we successfully assayed human plasma 5-HT by ultrafiltration and microbore liquid chromatography-electrochemical detection (10). The objective of this study was to apply this pretreatment procedure to the measurement of plasma 5-HT and 5-HIAA in healthy subjects and cancer patients.
Blood samples from 165 healthy subjects (65 women and 100 men; age range, 25–79 years) and from 40 cancer patients (21 women and 19 men; age range, 25–76 years) were collected and centrifuged immediately to separate plasma (1000g for 20 min at 4 °C). Informed consent was obtained from each person before this study. Of those patients specified as having intestinal cancers, 8 had gastric cancers and 17 had colon cancers. Two patients with early cancers (limited within submucosal layer) and 11 patients with advanced cancers received excision of the primary tumor and lymph node dissection. Twelve patients were considered unresectable because of invasion to vital organs or distant metastasis; these patients received either palliative or bypass surgery. Patients with carcinoid tumors were excluded from this study.
The liquid chromatography system was composed of a Beckman 126 pump (flow rate, 50 µL/min), a BAS-4C amperometric detector (set at +0.75 V; Bioanalytical Systems), and a microbore column (Inertsil-2, 5-µm octadecylsilane, 100 x 1.0 mm; G.L. Sciences) (10). The mobile phase consisted of 75 mL of acetonitrile, 5 mL of tetrahydrofuran, 2.2 mmol/L sodium 1-octanesulfonate, 14.7 mmol/L monosodium dihydrogen orthophosphate, 30 mmol/L sodium citrate, 0.027 mmol/L EDTA, and 1 mL of triethylamine in 1 liter of doubly distilled water (adjusted to pH 3.5). Plasma 5-HT and 5-HIAA were calculated by determining each peak-area ratio relative to the internal standard, 3-methoxytyramine. Statistical evaluation was performed using unpaired Student t-tests, and P <0.05 was accepted as significant.
Plasma 5-HT and 5-HIAA concentrations in the 165 healthy individuals
were 0.62 ± 0.11 and 1.94 ± 0.09 µg/L (mean ± SE),
respectively (Table 1
). The plasma 5-HT concentrations (6.26 ± 1.59 µg/L) in
cancer patients (both intestinal cancer and hepatoma; n = 40) were
significantly higher (P <0.05) when compared with healthy
subjects. The plasma 5-HT concentrations of patients with intestinal
cancer (n = 25) were significantly higher (6.96 ± 2.26
µg/L) when compared with healthy subjects. Lembeck (11)
reported increased plasma 5-HT in a patient with carcinoid tumor. The
secretion rate of 5-HT by a carcinoid tumor could exceed the maximum
uptake capacity of platelets, leading to increased plasma 5-HT
(12)(13). Thus, the 5-HT produced by the tumor
might first occupy all available binding sites on platelets before
circulating as free plasma 5-HT. However, the 5-HT concentrations
decreased dramatically to 1.96 ± 0.78 µg/L after surgery to
remove cancer cells from patients with intestinal cancer (n = 13).
Our data suggested that removing these cancer cells from patients might
limit the production of circulating 5-HT. The plasma 5-HIAA
concentrations did not change significantly after surgery in the above
intestinal cancer patients. However, Page et al. (14)
demonstrated an increased plasma 5-HIAA concentration in a carcinoid
patient with atypical facial flush.
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The application of the present assay allowed the measurement of very low concentration of plasma 5-HT and 5-HIAA. Plasma 5-HT may serve as a biomarker for patients with cancer, especially for intestinal cancers in the present study. Follow-up examinations and further investigations of the plasma 5-HT concentrations of those patients with intestinal cancers after dissection surgery are warranted.
Acknowledgments
This study was supported by Taichung Veterans General Hospital (Grant TCVGH-885901A) of Taiwan, the Republic of China.
References
The following articles in journals at HighWire Press have cited this article:
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  M. I Bennett, H. J Livingstone, P. Costello, K. R Allen, and T. J Degg Symptom scores, serotonin and 5-hydroxyindole acetic acid levels in cancer patients with and without bowel obstruction Palliative Medicine, March 1, 2007; 21(2): 157 - 159. [PDF]
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 M. Humbert, P. Labrune, O. Sitbon, C. Le Gall, J. Callebert, P. Herve, D. Samuel, R. Machado, R. Trembath, L. Drouet, et al. Pulmonary arterial hypertension and type-I glycogen-storage disease: the serotonin hypothesis Eur. Respir. J., July 1, 2002; 20(1): 59 - 65. [Abstract] [Full Text] [PDF]
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 I. P. Kema, W. G. Meijer, G. Meiborg, B. Ooms, P. H.B. Willemse, and E. G.E. de Vries Profiling of Tryptophan-related Plasma Indoles in Patients with Carcinoid Tumors by Automated, On-Line, Solid-Phase Extraction and HPLC with Fluorescence Detection Clin. Chem., October 1, 2001; 47(10): 1811 - 1820. [Abstract] [Full Text] [PDF]
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