Prognostic relevance of Fédération Nationale des Centres de Lutte Contre le Cancer grade and MDM2 amplification levels in dedifferentiated liposarcoma: a study of 50 cases

Abstract

Dedifferentiated liposarcoma represents a form of liposarcoma composed of a non-lipogenic sarcoma associated with well-differentiated liposarcoma. The prognostic significance of histological grading of the dedifferentiated component remains to be elucidated due to vague grading criteria employed in previous studies. Molecular markers of tumor behavior, including amplification levels of murine double minute-2 (MDM2) and cyclindependent kinase-4 (CDK4) genes, have been explored in a limited number of cases. Here we investigate whether 'Fédération Nationale des Centres de Lutte Contre le Cancer' (FNCLCC) grade and MDM2 gene amplification levels have prognostic value in dedifferentiated liposarcoma in terms of local recurrence and disease-specific survival. Fifty cases were retrieved, reviewed and FNCLCC grade was scored for the dedifferentiated component. Testing for MDM2 gene amplification was performed by fluorescence in situ hybridization. Amplification was categorized as high level (Z20 copies) and as low level (o20 copies). Follow-up data was obtained through chart review. Log-rank test and Cox proportional hazard models were used to determine the effect of grade and level of MDM2 amplification on outcomes. Our series includes 50 patients (male n ¼ 28, female n ¼ 22) with an average age of 63 years (range, 28-88) and a median follow-up of 28 months (range, 2-120). Tumors were graded as grade 1 (6%), grade 2 (58%), and grade 3 (36%). When adjusted for age, sex, site, tumor size, and margin status, grade 3 patients had a higher recurrence rate than grades 1 and 2 (HR ¼ 2.07, 95% CI: 1.24, 7.62; P ¼ 0.015). Patients with high-level MDM2 amplification had higher recurrence rate on univariate analysis (P ¼ 0.028), but not on multivariate analysis (HR ¼ 1.69, 95% CI: 0.73, 3.94; P ¼ 0.221). FNCLCC grade 3 dedifferentiation confers a worse prognosis in dedifferentiated liposarcoma in terms of local recurrence. MDM2 amplification level remains a useful diagnostic tool in dedifferentiated liposarcoma, but has no prognostic value in terms of local recurrence.

Osteogenic differentiation in dedifferentiated liposarcoma: a study of 36 cases in comparison to the cases without ossification

“…However, the follow‐up periods of this study might not be long enough to assess true life outcomes. High histological grade and a retroperitoneal tumour location have been reported repeatedly to be associated with worse outcomes in DDLPS . In our study, histological grade was the most important prognostic factor, while retroperitoneal tumour location was related only to shorter LRFS.…”

“…Histological examinations were performed using specimens taken by tumour resection, except for two ossified cases whose resection specimens were unavailable. Histological tumour grading was performed only in the cases without antecedent chemotherapy or radiotherapy, using a modified French Fédération Nationale des Centers de Lutte Contre le Cancer (FNCLCC) histological grading system in which the tumour differentiation score of the FNCLCC system was replaced by a tumour atypia score …”

Up-regulation of annexin A2 expression predicates advanced clinicopathological features and poor prognosis in hepatocellular carcinoma

“…ANXA2 staining score was the product of the intensity and percentage scores. The cutoff point for a statistically significant ANXA2 expression score in terms of survival was set using the X-tile software program and defined as follows: negative (−): (0-4), weakly positive (+): (4-6), moderately positive (++): (6-9), and strongly positive (9)(10)(11)(12). The staining in HCC and benign liver diseases tissues was scored independently by the two individuals who were blinded to each other's findings and the clinical characteristics of these sections (left panel, ×40, bar 500 μm; right panel, ×400, bar 50 μm) (χ 2 =46.305, P<0.001), single tumor node (χ 2 =7.707, P= 0.005), and early TNM stage (χ 2 =44.188, P<0.001), without intrahepatic metastasis (χ 2 =8.534, P=0.003) and portal vein tumor thrombus (χ 2 =19.988, P<0.001) had a significantly better prognosis (Fig.…”

“…Therefore, the early diagnosis is the only hope for curative therapies before metastasis of HCC is finally conquered [5], but the most important thing is to effectively screen out high-risk population for HCC according to prognostic factor [6]. With the increasing understanding of tumor biology of HCC, many new prognostic biomarkers of HCC [7,8] have been successively identified by clinical and/or pathological staging systems [9,10]. The identification of these genetic and epigenetic abnormalities in HCC Haijian Zhang and Min Yao contributed equally to this work.…”

A newly emerged osteosarcomatous dedifferentiation of liposarcoma in lung metastasis ‐ a potential diagnostic pitfall

“…Concerning the prognostic relevance of MDM2/CDK4 amplification in liposarcoma, a higher level of amplification seems to be associated with worse prognosis but has been reported not to be a statistically significant prognostic factor. 4,5 According to the previous CGH study, Forus et al reported that gain of chromosome 1q showed relation to metastasis. 2 We think that there is not a single strong predictive biomarker of clinical outcome in dedifferentiated liposarcoma.…”