Prognostic significance of CD44v5 expression in human thymic epithelial neoplasms.
BACKGROUND
Cell surface glycoproteins of the CD44 family play roles in cell-cell and cell-matrix interactions. Their aberrant expression has been implicated in tumor invasion and metastasis of a variety of neoplasms, but not, to date, of thymic epithelial tumors.


METHODS
To investigate the expression of CD44 molecules, immunohistochemical staining using monoclonal antibodies against human CD44 standard form (CD44 s) and two common splicing variant (CD44v) isoforms, CD44v5 and CD44v6, was performed on 64 resected thymomas and 20 normal thymuses. These tumors were categorized histologically according to the World Health Organization (WHO) histologic classification, and the pathologic staging was classified according to the definitions of Masaoka.


RESULTS
The positive expression rates in these patients were as follows: CD44 s (normal thymuses, 10%; thymomas, 22%), CD44v5 (normal thymuses, 0%; thymomas, 67%), and CD44v6 (normal thymuses, 0%; thymomas, 26%). CD44 s and CD44v5 immunoreactivity showed a positive correlation with tumor stages (p = 0.034 and 0.027, respectively). The CD44v5 expression of neoplastic cells in tumor capsules has significant correlation with tumor stages (II, 5%; III, 70%; IVA, 100%; p < 0.001). On the basis of univariate survival analysis, the Masaoka staging system, WHO histologic classification, and CD44v5 expression showed a statistically significant positive relation to survival (p < 0.001, 0.002, 0.011, respectively). Using Cox's regression model, increasing CD44v5 expression, the Masaoka staging, and the WHO classification system were found to be significant independent prognostic factors.


CONCLUSIONS
CD44v5 expression is independently positively correlated with the aggressiveness of thymic epithelial tumors. The expression of CD44v5 may be a potential trigger of tumor invasion in thymomas.
Lee
Shih-Chun
SC
Division of Thoracic Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Harn
Horng-Jyh
HJ
Lin
Torng-Sen
TS
Yeh
Kun-Tu
KT
Liu
Yao-Chi
YC
Tsai
Chien-Sung
CS
Cheng
Yeung-Leung
YL
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D001707:Biopsy, Needle; D015331:Cohort Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics*; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011110:Polymorphism, Genetic; D011336:Probability; D011379:Prognosis; D016016:Proportional Hazards Models; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D013953:Thymus Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology
D014408:Biomarkers, Tumor; C113800:CD44v5 antigen; D018960:Hyaluronan Receptors