Plasma glutathione S-Transferase P1-1 as a prognostic factor in patients with advanced non-Hodgkin's lymphoma (stages III and IV).
OBJECTIVE
This study aims to investigate whether the plasma level of glutathione S-transferase P1-1 (GSTP1-1), which is a phase II detoxifying enzyme known to be a resistance factor for anticancer drugs, could be a prognostic factor of de novo non-Hodgkin lymphoma (NHL) in clinical stages (CSs) III and IV.


METHODS
Study population consisted of 80 NHL patients with no prior treatment: 12 patients were at CS I, 14 at CS II, 25 at CS III, and 29 at CS IV. All 54 patients at CS III or CS IV were treated with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). Plasma GSTP1-1 concentration was measured by ELISA. We stained lymph node tissues for GSTP1-1 using anti-GSTP1-1 monoclonal antibody 5F and quantitatively assessed the intensity of immunostaining by using the KS-400 image analyzing system.


RESULTS
There was a significant stepwise increment of plasma GSTP1-1 concentration from CS I to CS IV (P < 0.05). Of the 54 patients with CS III or IV treated with CHOP, 28 (52%) had elevated plasma GSTP1-1 levels. Plasma GSTP1-1 concentration tended to correlate with the intensity of GSTP1-1 expression in lymphoma tissues as assessed by immunostaining (P = 0.07). The CR rates in patients at CS III and CS IV treated by CHOP, 55.2% (14 of 26) and 16.0% (5 of 28) for the low and high plasma GSTP1-1 groups, respectively, were significantly different (P < 0.01). For these two groups, the median survival times were 64 and 25 months, respectively (P < 0.01), and the median times to progression were 58 and 12 months, respectively (P < 0.01). There was no significant correlation between plasma GSTP1-1 concentrations and other NHL prognostic indicators in these patients as determined by univariate and multivariate analyses.


CONCLUSIONS
These results showed that plasma GSTP1-1 is a useful prognostic factor for CS III and IV advanced NHL. Thus, it may be a promising strategy to treat NHL concomitantly with anticancer drugs and GSTP1-1-specific inhibitors.
Katahira
Tatsuro
T
Fourth Department of Internal Medicine, Sapporo Medical University, School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, Japan.
Takayama
Tetsuji
T
Miyanishi
Koji
K
Hayashi
Tsuyoshi
T
Ikeda
Tatsuru
T
Takahashi
Yasuo
Y
Takimoto
Rishu
R
Matsunaga
Takuya
T
Kato
Junji
J
Niitsu
Yoshiro
Y
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use*; D018450:Disease Progression; D004317:Doxorubicin / Q000627:therapeutic use*; D005260:Female; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000097:blood*; D006801:Humans; D007527:Isoenzymes / Q000097:blood*; D016393:Lymphoma, B-Cell / Q000175:diagnosis* / Q000188:drug therapy / Q000201:enzymology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis* / Q000188:drug therapy / Q000201:enzymology; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis* / Q000188:drug therapy / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use*; D011379:Prognosis; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D014750:Vincristine / Q000627:therapeutic use*
D007527:Isoenzymes; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D011241:Prednisone