Prognostic significance of p53 and matrix metalloproteinase-9 expression in follicular lymphoma.
OBJECTIVE
p53 mutations and high protein expression are associated with adverse prognosis in several lymphoma subtypes. Matrix metalloproteinase-9 (MMP-9) has also been found to correlate with poor survival in all lymphomas studied. The data concerning the clinical role of protein expression of p53 or gelatinases and their inhibitors in follicular lymphoma are rare. The purpose of this study was to evaluate the prognostic and clinical implications of the immunoreactive proteins p53, MMP-2, MMP-9, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and TIMP-2 in follicular lymphoma.


METHODS
The material consisted of 67 patients with primarily non-transformed follicular lymphoma. Diagnostic lymph node tissue sections of patients were stained by immunohistochemical method using specific monoclonal antibodies.


RESULTS
p53 over-expression was detected in 8 (12%) out of 67 cases. p53 over-expression correlated with high grade (P = 0.011), bulky tumour (P = 0.031) and forthcoming transformation (P = 0.001). It also correlated with poor overall (P = 0.001) and cause-specific survival (P = 0.010) in multivariate analysis and had a strong inverse correlation with time to transformation (P < 0.001). MMP-2, MMP-9 and TIMP-2 expression correlated with high grade. MMP-9 positivity in centroblasts correlated with good chemotherapy response (P = 0.019), but it was not prognostic for survival. MMP-2, TIMP-1 or TIMP-2 did not associate with survival, either.


CONCLUSIONS
In this study, p53 over-expression predicted both transformation to diffuse large B-cell lymphoma and poorer overall and cause-specific survival of patients with follicular lymphoma. Expression of gelatinases or their inhibitors did not have any significant correlations with prognosis, although MMP-9 predicted a good response to first-line chemotherapy.
Pennanen
Heli
H
Department of Oncology and Radiotherapy, University of Oulu and Oulu University Hospital, Oulu, Finland. heli@kyllonen.fi
Kuittinen
Outi
O
Soini
Ylermi
Y
Turpeenniemi-Hujanen
Taina
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007120:Immunochemistry; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008224:Lymphoma, Follicular / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D015996:Survival Rate; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
C495901:TP53 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D016159:Tumor Suppressor Protein p53; D019716:Tissue Inhibitor of Metalloproteinase-2; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9