Retention of dopamine 2 receptor mRNA and absence of the protein in craniospinal and extracranial metastasis of a malignant prolactinoma: a case report.
OBJECTIVE
The case presented here describes the clinical evolution of a malignant prolactinoma with occurrence of intra- and extra-cranial metastases. In this case, the presence of dopamine 2 receptor (D2R) was studied at the mRNA and protein level, in order to understand the pathological background of the resistance to treatment with different dopamine agonists.


METHODS
Together with an extensive description of the clinical history of this case, a combination of in vitro and in vivo techniques was performed to provide the basis of the dopamine resistance developed in the course of the disease.


METHODS
A comparison of the D2R was performed in specimens obtained at presentation of the disease compared with autoptic specimens derived from local invasion and metastasis using in situ hybridization and immunohistochemical techniques.


RESULTS
Intact D2R mRNA was found in the primitive tumor and metastatic tissues, whereas protein for the same receptor was present only in the tissues derived from neurosurgical operations and not in the metastases obtained post-mortem.


CONCLUSIONS
This is the first report of the absence of D2R protein despite the retention of the transcript in an advanced stage of a malignant prolactinoma. The findings of this single case suggest the hypothesis that postranscriptional mechanisms may contribute to the development of dopamine resistance in prolactinomas.
Winkelmann
J
J
Department of Neurology, Max-Planck-Institute of Psychiatry, Kraepelinstrasse 10, 80804 Munich, Germany. janew@mpipsykl.mpg.de
Pagotto
U
U
Theodoropoulou
M
M
Tatsch
K
K
Saeger
W
W
Müller
A
A
Arzberger
T
T
Schaaf
L
L
Schumann
E M
EM
Trenkwalder
C
C
Stalla
G K
GK
D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary*; D001971:Bromocriptine / Q000627:therapeutic use; D018491:Dopamine Agonists / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000134:cerebrospinal fluid / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000473:pathology; D011388:Prolactin / Q000097:blood; D015175:Prolactinoma / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000134:cerebrospinal fluid; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis*; D013125:Spinal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary*; D014786:Vision Disorders / Q000209:etiology
D018491:Dopamine Agonists; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D001971:Bromocriptine; D011388:Prolactin