Increased CD44s and decreased CD44v6 RNA expression are associated with better survival in myxofibrosarcoma patients: a pilot study.
BACKGROUND
New prognostic markers may be of value in determining survival and informing decisions of adjuvant treatment in the heterogeneous group of soft tissue sarcomas known as malignant fibrous sarcomas (MFS). Increased CD44 expression has been associated with a better outcome in cancers such as bladder tumors and could potentially relate to cell-cell interaction as a marker for potential invasion/metastasis. The aim of this pilot study was to determine if there is a correlation between the expression rate of CD44 in adult patients with MFS and clinical outcomes.


METHODS
The clinical outcome of 34 adult MFS patients (19 males and 15 females, average age 62 years, median 63 years, range: 38-88 years) who underwent surgical treatment were evaluated. Twenty-five of these patients had additional adjuvant radiotherapy. Extracted RNA from sarcoma tissues was used to measure the transcripts of CD44s (standard form) and isoform expression.The pooled data for each variant of CD44 was divided in half at the median expression value into two equally sized groups (low and high). Survival modeling and multivariate analysis were used with these two groups to determine if there were differences in survival times and whether this was independent of known factors such as tumor stage/grade, patient age and resection margin status.


RESULTS
High CD44s and low of CD44v6 expression significantly correlated with an improved outcome (P <0.05 and P <0.02, respectively) whereas CD44v8 and hCD44 (isoforms) did not. Differences in survival were apparent within 6-12 months of operation with >30% difference in survival between low/high expressions at 5 years. These finding were independent of the other measured MFS survival predictors, though the group was homogenous.


CONCLUSIONS
High CD44s and low CD44v6 expression may be an independent predictor of improved survival in MFS patients in this pilot data. This is contrary to other MFS data, which did not account for the CD44 isoforms but is confirmed by data from other cancer types. Further investigation is needed to confirm CD44 isoform expression data as a relevant survival biomarker and whether it could be used to inform clinical decisions such as adjuvant therapy.
Christiane
C
Matuschek
Marcus
M
Lehnhardt
Peter Arne
PA
Gerber
Christopher
C
Poremba
Jackson
J
Hamilton
Guido
G
Lammering
Klaus
K
Orth
Wilfried
W
Budach
Hans
H
Bojar
Edwin
E
Bölke
Klinik für Allgemein-, Viszeral- und Kinderchirurgie, Universitätsklinikum Düsseldorf, Moorenstraße 5, 40225 Düsseldorf, Germany. m.peiper@kliniken-essen-sued.de.
Matthias
M
Peiper
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D005354:Fibrosarcoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis / Q000096:biosynthesis*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011379:Prognosis; D016016:Proportional Hazards Models; D020033:Protein Isoforms; D012313:RNA / Q000032:analysis; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D020033:Protein Isoforms; D012313:RNA