Matrix metalloproteinases in carcinoma of unknown primary.
BACKGROUND
The purpose was to study proteolysis-related molecules, matrix metalloproteinase-2 (MMP-2) and MMP-9 and tissue inhibitor of metalloproteinases-1 (TIMP-1), in carcinoma of unknown primary (CUP).


METHODS
Paraffin-embedded tumor material from 75 patients diagnosed with CUP was used. Tumor histologies were adenocarcinoma (77%), undifferentiated carcinoma (19%), and squamous cell carcinoma (4%) and patients were categorized into favorable (62%) and unfavorable (38%) subsets. The tissue expression of MMP-2, MMP-9, and TIMP-1 was assessed by use of specific monoclonal antibodies and evaluated by means of a visual staining score. The expression of molecules studied was analyzed against clinicopathological data.


RESULTS
MMP-2 was found expressed in 69% (strong expression in 49%), MMP-9 in 49% (strong in 36%), and TIMP-1 in 79% (strong in 44%) of studied cases. The expression of MMP-2 correlated positively with MMP-9. TIMP-1 was significantly higher in unfavorable compared with favorable tumors and was associated with a shorter survival of patients (7.5 vs. 12 mos). No other associations were detected.


CONCLUSIONS
MMP-2, MMP-9, and TIMP-1 are widely expressed in CUP, suggesting an essential role of proteolysis in these tumors. TIMP-1 may be considered a possible marker of poor prognosis in CUP patients.
Karavasilis
Vasilis
V
Medical Oncology Department, Ioannina University Hospital, Ioannina, Greece.
Malamou-Mitsi
Vasiliki
V
Briasoulis
Evangelos
E
Tsanou
Elena
E
Kitsou
Evangelia
E
Kalofonos
Haralambos
H
Fountzilas
George
G
Fotsis
Theodore
T
Pavlidis
Nicholas
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002277:Carcinoma / Q000201:enzymology* / Q000556:secondary*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000201:enzymology*; D011379:Prognosis; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism
D014408:Biomarkers, Tumor; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases