Grading of soft tissue sarcomas: from histological to molecular assessment

Several histological grading systems for soft tissue sarcomas have been described since the early 1980s. Their main objective is to select patients for adjuvant chemotherapy. Two histological grading systems are used in daily practice, the National Cancer Institute (NCI) and the French Federation of Cancer Centers Sarcoma Group (FNCLCC) systems. They have been devised by combining histological parameters: number of mitoses per high-power field, the presence of necrosis, cellular and nuclear morphology and the degree of cellularity for the NCI grading; and tumour differentiation, mitotic index and extent of necrosis for the French system. Histological grading is far more appropriate to assess the risk of metastasis. However, several limitations prevent its use: grade cannot be applied to all histological types, its reproducibility is not perfect, a three-grade system generates an intermediate grade with undetermined prognosis, and finally the core needle biopsy, now widely used for the diagnosis of soft tissue sarcoma, is not the best sample to assess the grade. The development of molecular grading in addition to histological grading probably represents the next step. Molecular signatures based on quantitative evaluation of chromosomal complexity such as CINSARC (complexity index in sarcomas) appear as a strong independent predictive factor for metastasis in several types of sarcoma, and even in several other types of cancer. When they can be instituted in daily practice on formalin fixed, paraffin embedded material, molecular signatures will not only provide information on risk of metastasis, but also better understanding of cancer development, response or resistance to evaluated drugs, and potential targets for future treatments.