The CD99 protein is ubiquitously expressed in a variety of human normal tissues and malignant cells (21
). In normal tissue CD99 is highly expressed in cortical thymocytes, pancreatic islet cells, granulosa cells of the ovary, Sertoli's cells and ependymal cells. It is also expressed on fibroblasts, endothelial cells, smooth muscle cells and respiratory epithelial cells in which the level of expression is relatively low (24
). Even though CD99 is known to be a specific marker for Ewing/PNET, it is expressed in a variety of tumors (20
). With respect to neoplasms of the lung, CD99 is expressed in 25% of pulmonary neuroendocrine tumors and is preferentially confined to typical carcinoids (19
). It is generally accepted that CD99 is not a specific marker for a particular subset of neoplasms. The present study demonstrates that CD99 expression is not only shown by spindle cells and giant cells in PCL, rather all cases containing a carcinomatous component showed various degrees of CD 99 positivity. In terms of sarcomatous component, the percentage of CD99-positive cells was higher in spindle cells than in giant cells. Our results support the concept that CD99/MIC-2 is not a specific marker for distinguishing a particular subset of human tumors. Moreover, it has been reported that CD99 plays critical role in the invasion, motility, and proliferation of malignant cells (27
). Pelosi et al. reported a statistically significant relationship between the number of CD99 positive cells and the presence of local invasion and/or distant metastasis, and the Ki-67 index in gastrointestinal and pulmonary neuroendocrine tumors (19
). These findings suggest that CD99 may be involved in cell-to-cell adhesion of neuroendocrine tumor cells and in downregulation of their proliferative activity. Thus, to explore the biological implication of CD99 in PCL we analyzed patient clinico-pathologic data. However, CD99 expression in PCL was not found to be correlated with patient prognostic parameters. These findings suggest that the expression of CD99 in PCL does not contribute to the anti-proliferation PCL tumor cells.
Although the histogenesis of PCL has not been clearly explored, several groups have suggested the possibility that PCL is a carcinoma with divergent sarcomatous differentiation, rather than being a collision neoplasm. Recently Rossi et al. studied 58 cases of PCL that showed immunoreactivity for CK7 and TTF-1 in the epithelial and sarcomatous elements (34
). In addition, three groups have demonstrated that the epithelial and sarcomatous components of PCL show the same genetic abnormalities by microdissection analysis (35
). These findings support the concept that the sarcomatous components of PCL might be derived from epithelial components. Like CK7, CD99 was also expressed on spindle and/or giant cells as well as PCL carcinomas in the present study. However, these findings inadequately support the concept that spindle and giant cells are derived from carcinoma because CD99 is more widely expressed on human mesenchymal components and sarcomas than carcinomas. Thus, it is more likely that the expression of CD99 on sarcomatous component of PLC reflects tumor cell mesenchymal differentiation status.
In summary, CD 99 was found to be widely expressed in both sarcomatoid and epithelial components in PCL, like other epithelial markers. Although the biological implications of its expression in PCL remain unclear, the clinicopathological analysis demonstrated no direct correlation between the expressions of CD99 in PCL and the clinical indices of PCL patients.