Prediction of response to treatment in superficial bladder carcinoma through pattern of interleukin-2 gene expression.
OBJECTIVE
Superficial bladder carcinoma, treated by resection and intravesical administration of bacillus Calmette-Guérin (BCG), yields a remission rate that approaches 70%. We examined whether expression of interleukin-2 (IL-2) or interferon-gamma (IFN-gamma) genes can serve to predict response.


METHODS
During BCG treatment, we analyzed induction of IL-2 and IFN-gamma mRNA in peripheral-blood mononuclear cells (PBMC) from 73 patients: 51 with papillary tumors and 22 with carcinoma-in-situ (CIS). Results were correlated with remission, relapse, or tumor persistence over a 4-year follow-up period.


RESULTS
Independent of tumor type, induction of IL-2 mRNA was observed for patients who responded with remission, but not for those who relapsed (P = .0001). Multivariate logistic analysis showed that inducibility of IL-2 mRNA is the discriminating parameter, which yields a predictive value of 97% for remission. Of 23 patients with relapse/persistence, 22 lacked inducibility of IL-2 mRNA (sensitivity, 95.6%), while 35 of 50 patients in remission exhibited inducibility (specificity, 70%). For patients with carcinoma-in-situ, in which remission or failure depends solely on response to BCG, sensitivity and specificity were 88% and 86%, respectively; for patients with papillary tumors, they were 100% and 64%. IFN-gamma mRNA, by contrast, was clearly inducible in PBMC from all patients (P = .51). The disease-free interval increased progressively with inducibility of IL-2 mRNA; this trend was highly significant (P = .0001).


CONCLUSIONS
IL-2 gene expression is essential for mounting an antitumor response in superficial bladder carcinoma. Inducibility of IL-2 mRNA is an independent prognostic parameter and useful predictive indicator of remission versus relapse.
Kaempfer
R
R
Department of Molecular Virology, Hebrew University-Hadassah Medical School; Jerusalem; Israel. kaempfer@cc.huji.ac.il
Gerez
L
L
Farbstein
H
H
Madar
L
L
Hirschman
O
O
Nussinovich
R
R
Shapiro
A
A
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000283:Administration, Intravesical; D000368:Aged; D001345:Autoradiography; D001500:BCG Vaccine / Q000627:therapeutic use*; D002278:Carcinoma in Situ / Q000235:genetics / Q000473:pathology / Q000628:therapy; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D007376:Interleukin-2 / Q000032:analysis / Q000235:genetics*; D008297:Male; D009364:Neoplasm Recurrence, Local; D010835:Phytohemagglutinins; D011237:Predictive Value of Tests; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D012074:Remission Induction; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*
D000276:Adjuvants, Immunologic; D001500:BCG Vaccine; D007376:Interleukin-2; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D007371:Interferon-gamma