Histidine Decarboxylase, DOPA Decarboxylase, and Vesicular Monoamine Transporter 2 Expression in Neuroendocrine Tumors: Immunohistochemical Study and Gene Expression Analysis

Abstract

(GP) S U M M A R Y Histidine decarboxylase (HDC) and vesicular monoamine transporter 2 (v-MAT2) are involved in the biosynthesis and storage of histamine. DOPA decarboxylase (DDC) is involved in the biosynthesis of a variety of amines and shares a high degree of homology with HDC. HDC and v-MAT2 immunoreactivities (IR) have recently been detected in well-differentiated neuroendocrine tumors (WDNETs) and poorly differentiated neuroendocrine carcinomas (PDNECs) of various sites and have been proposed as general endocrine markers. We evaluated HDC and v-MAT2 IR in a series of 117 WDNETs and PDNECs from different sites. Western blotting analysis was performed to verify the specificity of anti-DDC and anti-HDC antibodies. Real-time RT-PCR was performed using specific probes for HDC and DDC on 42 cases, examined also for DDC IR. HDC and v-MAT2 IR were observed in the majority of WDNETs and PDNECs of all sites and HDC-IR cases were always also DDC-IR. In contrast, high levels of HDC mRNA were detected only in the gastroenteropancreatic WDNETs, which did not show increased DDC mRNA levels. On the other hand, bronchial carcinoids and lung PDNECs showed high DDC mRNA levels, but nearly undetectable HDC mRNA levels. Western blotting analysis showed a cross-reaction between anti-HDC and anti-DDC antibodies. HDC should not be considered as a general endocrine marker and HDC IR in bronchial carcinoids and PDNECs of the lung can probably be attributed to a cross-reaction with DDC.

Effect of Carbidopa on 18F-FDOPA Uptake in Insulinoma: From Cell Culture to Small-Animal PET Imaging

“…This finding indicates that the intracellular decarboxylation process in RIN-5mF cells was not considerably affected by the pharmacologic inhibition by carbidopa. The upregulation of AADC activity in NET cells supports this finding (10,17).…”

“…However, no final consensus about the usefulness of carbidopa premedication before 18 F-FDOPA PET in patients with hyperinsulinemic hypoglycemia has been reached because of the potential reduction of tumoral uptake intensity (9). The risk of 18 F-FDOPA PET false-negative results could be high for tumors with low intracellular AADC activity (10), which are potentially more sensitive to the inhibitory effect of carbidopa.…”

Clinical Value of 18F-FDOPA PET/CT With Contrast Enhancement and Without Carbidopa Premedication in Patients with Insulinoma

“…At our Department, in patients with HH and suspected insulinoma, 18 F-FDOPA-PET/CT with contrast enhancement, early acquisition time, and no carbidopa-premedication was performed. In the present study, we evaluated the clinical usefulness of 18 F-FDOPA-PET/CT with the abovementioned conditions that would make this method a 'onestop' examination.…”

“…In the present study, we evaluated the clinical usefulness of 18 F-FDOPA-PET/CT with the abovementioned conditions that would make this method a 'onestop' examination.…”

Quantitative expression analysis and prognostic significance of L-DOPA decarboxylase in colorectal adenocarcinoma

“…High DDC mRNA expression has been noticed in small-cell lung carcinoma (SCLC), neuroblastoma, and pheochromocytoma (Jensen et al, 1990;Gilbert et al, 1999;Uccella et al, 2006). Moreover, it has been suggested that DDC mRNA levels could be a potential biomarker for the detection of minimal residual disease in patients with neuroblastoma and for the discrimination of neuroblastoma from other small round-cell tumours of childhood (Gilbert et al, 1999;Bozzi et al, 2004).…”