Downregulation of CD99 and upregulation of human leukocyte antigen class II promote tumor aggravation and poor survival in patients with osteosarcomas

Abstract

Background: CD99 is involved in the intracellular transport of human leukocyte antigen class II (HLA-II) protein. The aim of this study was to clarify the clinical value of CD99 and HLA-II expression in primary osteosarcoma.

Methods: One hundred and thirty pairs of osteosarcoma and matched noncancerous bone tissues were evaluated by immunohistochemistry for CD99 and HLA-II expression.

Results: Compared with the noncancerous bone tissues, the expression levels of CD99 (tumor versus normal: 2.96±0.09 versus 5.89±1.26, P<0.001) and HLA-II (tumor versus normal: 5.01±1.39 versus 1.92±0.06, P<0.001) proteins were respectively downregulated and upregulated in osteosarcoma tissues. CD99 and HLA-II were highly expressed in 49/130 (37.69%) and 107/130 (82.31%) of osteosarcoma tissues, respectively. In addition, the osteosarcoma patients with downregulation of CD99 and upregulation of HLA-II more frequently showed the presence of metastasis and recurrence and poor response to chemotherapy. Moreover, there was a negative correlation between CD99 and HLA-II expression in osteosarcoma tissues (r=-0.69, P=0.01). The patients with low CD99 expression correlated with poor prognosis of osteosarcoma, as opposed to HLA-II. Patients with CD99-low/HLA-II-high expression had the lowest overall and disease-free survival rates, and conjoined expression of CD99/HLA-II was an independent prognostic indicator of osteosarcoma.

Conclusion: These findings suggest for the first time that CD99 downregulation or HLA-II upregulation may be an important feature of human osteosarcoma. The combined detection of CD99/HLA-II coexpression may present a predictive and prognostic indicator in osteosarcoma.

Keywords: CD99; HLA-II; immunohistochemistry; osteosarcoma; prognosis.

Figure 1

Immunohistochemical expression for CD99 and HLA-II in primary osteosarcoma tissues (×400). Notes: CD99 was weakly expressed in the cytoplasm and cell membrane of osteosarcoma cells (A). HLA-II was strongly expressed in the cytoplasm and cell membrane of osteosarcoma cells (B). The red arrows indicate the positive area in the osteosarcoma tissues. Abbreviation: HLA-II, human leukocyte antigen class II.

Figure 2

Kaplan–Meier survival curves of patients with primary osteosarcoma according to the expressions of CD99 (A and B) and HLA-II (C and D), and the coexpression of CD99/HLA-II (E and F). Notes: The osteosarcoma patients with low CD99 expression and high HLA-II expression were correlated with both shorter overall survival (both P<0.001) and shorter disease-free survival (both P<0.001). According to the conjoined expressions of CD99/HLA-II, the subjects were categorized into four groups: CD99-low/HLA-II-low (n=4), CD99-low/HLA-II-high (n=77), CD99-high/HLA-II-low (n=19), and CD99-high/HLA-II-high (n=30). The association between coexpression of CD99/HLA-II and the survival rates were also tested by the method of Kaplan–Meier. The results by pairwise comparisons showed that a statistically significant difference of survival rates existed between CD99-low/HLA-II-high cases and any of other three groups (P<0.001). In all four groups, CD99-low/HLA-II-high subjects had the poorest prognosis. Abbreviation: HLA-II, human leukocyte antigen class II.