Expression of metastasis suppressor gene maspin is reduced in breast cancer brain metastases and correlates with the estrogen receptor status.
OBJECTIVE
The suppressor gene maspin (Serpin B5) is a promising candidate for future treatment. We have examined the messenger RNA (mRNA) and protein expression of maspin in normal breast tissue, breast cancer primaries, brain metastases and breast cancer cell lines. Results were compared to hormone receptor expression and proliferation index.


METHODS
Maspin mRNA expression was examined by real-time polymerase chain reaction in fresh frozen human samples and breast cancer cell lines MCF-7, T47-D and MDA-MB-231. Maspin protein, estrogen and progesterone receptor expression as well as Ki-67 proliferation index were detected by immunohistochemistry from 16 patients with breast cancer primaries and breast cancer brain metastases.


RESULTS
In relation to normal breast tissue, maspin mRNA expression was decreased in primary tumors and again decreased in brain metastases. Normalized C(T) values were 1 (normal tissue), 0.3 (primary tumors) and 0.13 (brain metastases). Immunohistochemistry revealed same tendencies. In comparison to poorly invasive breast cancer cell lines, maspin mRNA expression was decreased in highly invasive and metastatic 231-parental cell lines. In contrast, maspin mRNA expression was increased in 231-brain, and it was not detectable in 231-bone. Patients with maspin-positive primary tumors showed longer survival.


CONCLUSIONS
This finding adds maspin to the list of metastasis suppressor genes possibly involved in the formation of breast cancer brain metastases.
Stark
Andreas M
AM
Department of Neurosurgery, University of Schleswig-Holstein Medical Center, Campus Kiel, Schittenhelmstrasse 10, 24105 Kiel, Germany.
Schem
Christian
C
Maass
Nicolai
N
Hugo
H H
HH
Jonat
Walter
W
Mehdorn
H Maximilian
HM
Held-Feindt
Janka
J
D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D001932:Brain Neoplasms / Q000378:metabolism / Q000556:secondary* / Q000628:therapy; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D003399:Craniotomy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D011960:Receptors, Estrogen / Q000096:biosynthesis*; D011980:Receptors, Progesterone / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015843:Serpins / Q000096:biosynthesis*
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C085344:SERPIN-B5; D015843:Serpins