Improved demonstration of immunohistochemical prognostic markers for survival in follicular lymphoma cells.
Follicular lymphoma (FL) is one of the most common forms of the low-grade non-Hodgkin's lymphoma in adults, with a characteristic translocation, t(14;18)(q32;q21) that deregulates the expression of the BCL2 gene. The clinical course of FL patients is variable, whereby a subset of patients survive for long periods even without relapses, whereas the majority have frequent relapses with shorter survival. We have analyzed a series of 186 FLs, studying the correlation between clinical outcome and the tumor cell expression of a set of immunohistochemical markers, using an automated procedure for tissue microarrays to reduce the subjectivity of scoring. The results identified several markers associated with differences in overall survival (OS) in univariate analyses, such as Cyclin E, Mdm2, CD10, p21, IgD, Bcl-xL, CD30, and E2F6. Cases with a higher level of expression of Cyclin E, Mdm2, p21, IgD, Bcl-xL, CD30, and E2F6 were associated with a significantly shorter OS. On the other hand, strong CD10 expression was linked to a significantly better outcome. A Cox model was then constructed, integrating the Follicular Lymphoma International Prognostic Index (FLIPI) score and a restricted selection of three immunohistochemical markers: Cyclin E, Mdm2, and CD10 expression. A potentially useful finding is that the integrated FLIPI plus immunohistochemical model can be used to identify a subset of 26 patients (almost 20% of the total series), with a survival probability of 100% at 5 years. This not only confirms that a group of FL cases may have a very good clinical course, but also indicates that this group can be identified using this integrated clinical and immunohistochemical approach.
Department of Pathology, Hospital Universitario de Getafe, Carretera de Toledo, Getafe, Madrid, Spain. ficamacho.hugf@salud.madrid.org
Francisca I
FI
Camacho
Carmen
C
Bellas
Cesáreo
C
Corbacho
Alexia
A
Caleo
Reyes
R
Arranz-Sáez
Jimena
J
Cannata
Javier
J
Menárguez
Lydia
L
Sánchez-Verde
Leocricia
L
González-Camacho
M Elena
ME
Pérez-Martín
Miguel A
MA
Martínez-González
Tomás
T
Alvaro
Manuela
M
Mollejo
Carmen
C
Ruíz-Marcellán
Carlos
C
Montalbán
Miguel A
MA
Piris
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008224:Lymphoma, Follicular / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D013030:Spain / Q000453:epidemiology; D015996:Survival Rate; D046888:Tissue Array Analysis; D055815:Young Adult
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins