Besides molecular genetic alterations, both low-grade and high-grade serous carcinomas are characterized by distinct gene expression profiles. For example, transcriptome-wide gene expression profiling has demonstrated that human leukocyte antigen-G (HLA-G) is overexpressed in many high-grade serous carcinomas but rarely in low-grade serous carcinomas. HLA-G immunoreactivity, ranging from focal to diffuse, was detected in most high-grade ovarian serous carcinomas but not in any low-grade serous carcinomas or serous borderline tumors (atypical proliferative serous tumors ) and noninvasive low-grade serous carcinomas).35 A similar correlation of HLA-G expression with behavior has been observed in large cell carcinomas.36 A possible mechanism that explains the association of HLA-G expression with highgrade serous carcinomas is that HLA-G seems to facilitate tumor cell evasion of the immune system by protecting malignant cells from being attacked by immune cells.37
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