Expression of Histidine Decarboxylase and Synthesis of Histamine by Human Small Cell Lung Carcinoma

Graff, Lothar; Frungieri, Mónica Beatriz; Zanner, Robert; Pohlinger, Agnes; Prinz, Christian; Gratzl, Manfred

doi:10.1016/s0002-9440(10)61102-9

Cited by 53 publications

(44 citation statements)

References 19 publications

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“…In fact, expression of both v-MAT2 and HDC is a feature of histaminehandling cells (Medina et al 2003) and represents a strong indicator of histamine production in NETs from sites different from the stomach. Moreover, such widespread expression of v-MAT2 and HDC in NETs suggests that they may be considered as new general endocrine markers, as previously proposed by other authors (Graff et al 2001(Graff et al ,2002Matsuki et al 2003;Tanimoto et al 2004).…”

Section: Discussionsupporting

confidence: 61%

“…On the other hand, all available data on IHC expression of HDC in NETs have been obtained using polyclonal antibodies directed against human recombinant L-HDC expressed in E. coli (Graff et al 2002;Matsuki et al 2003;Tanimoto et al 2004), one of which was also employed in the present study. The possibility of a cross-reaction of this antibody with DDC should be considered due to the large PLPdependent domain shared by the two enzymes, which are evolutionary related as they derive from the same ancestor gene (Saenz-de-Miera and Ayala 2004).…”

Section: Discussionmentioning

confidence: 99%

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

Uccella

Cerutti

Vigetti

et al. 2006

J Histochem Cytochem.

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(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.

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Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

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

Uccella

Cerutti

Vigetti

et al. 2006

J Histochem Cytochem.

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“…These findings suggest the possibility that HDC may be another marker for neuroendocrine differentiation. One recent study has revealed the expression of HDC in biopsied materials of small cell lung carcinoma (25). To our knowledge, however, no systematic immunohistochemical study of HDC expression in neuroendocrine or endocrine tumors has been reported.…”

mentioning

confidence: 95%

Histidine Decarboxylase Expression as a New Sensitive and Specific Marker for Small Cell Lung Carcinoma

et al. 2003

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Histidine decarboxylase is one of the enzymes of the amine precursor uptake and decarboxylation system and is known to be distributed in mast cells and enterochromaffin-like cells. With the hypothesis that histidine decarboxylase expression is a marker for neuroendocrine differentiation, we studied the immunoreactivity of histidine decarboxylase in neuroendocrine cells and tumors of the thyroid gland, adrenal medulla, lung, and gastrointestinal tract. Formalin-fixed paraffin sections were subjected to immunohistochemistry using antihistidine decarboxylase antibody, and the sensitivity and specificity were compared with those of conventional neuroendocrine markers (CD56, chromogranin A, synaptophysin, and neuron-specific enolase). Enterochromaffin or enterochromaffinlike cells, adrenal chromaffin cells, and thyroid C-cells were positive for histidine decarboxylase, and related tumors (carcinoid tumor, pheochromocytoma, medullary carcinoma) showed a high percentage of positive staining. Furthermore, we used the antibody to distinguish small cell lung carcinoma from non-neuroendocrine lung carcinoma and also to detect neuroendocrine differentiation in large-cell neuroendocrine carcinoma and gastrointestinal small-cell carcinoma. The anti-histidine decarboxylase antibody stained most small cell lung carcinoma (18 of 23, sensitivity 0.78), and was rarely reactive with non-neuroendocrine lung tumors (2 of 44; specificity, 0.95). These values were close to those obtained from CD56 staining (sensitivity/ specificity, 0.87/0.98). Histidine decarboxylase was also positive for 6 of 12 large cell neuroendocrine carcinomas and 4 of 7 gastrointestinal small cell carcinomas. In conclusion, we demonstrated that histidine decarboxylase is useful to distinguish between small cell lung carcinoma and nonneuroendocrine carcinoma and to demonstrate neuroendocrine differentiation.

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“…Mientras los síndromes endocrinos por producción ectópi-ca de hormonas son frecuentes en los tumores neuroendocrinos pulmonares, especialmente de ACTH, en nuestro caso no se detectó producción ectópica de hormonas, hecho ya descrito en trabajos previos en relación con el carcinoma neuroendocrino de células grandes, aunque sí se detectaron niveles muy elevados de histamina, la cual se ha implicado en alguna ocasión en la patogenia del "flushing" en el síndrome carcinoide asociado a carcinoides gástricos (4) e ileales (5) sintetizada, almacenada y liberada en cultivos celulares de carcinomas de células pequeñas (6).…”

Section: Discussionunclassified

Eritema generalizado, masa pulmonar e inguinal como forma de presentación de un carcinoma neuroendocrino pulmonar de células grandes

Villar¹,

López²,

Márquez³

et al. 2004

An. Med. Interna (Madrid)

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Expression of Histidine Decarboxylase and Synthesis of Histamine by Human Small Cell Lung Carcinoma

Cited by 53 publications

References 19 publications

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

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

Histidine Decarboxylase Expression as a New Sensitive and Specific Marker for Small Cell Lung Carcinoma

Eritema generalizado, masa pulmonar e inguinal como forma de presentación de un carcinoma neuroendocrino pulmonar de células grandes

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