P16 as a marker to differentiate atypical lipomatous tumor/well-differentiated liposarcoma from deep seated lipoma: An immunohistochemical analysis of 51 cases

Abstract

10070 Background: Atypical lipomatous tumor (ALT)/well-differentiated (WD) liposarcoma is a locally aggressive malignant mesenchymal neoplasm characterized by supernumerary ring and giant marker chromosomes with amplification of MDM2 gene. These cytogenetic characteristics can be very helpful to distinguish ALT from deep-seated lipomas. As ALTs have only rare presence of lipoblasts, they can resemble benign lipomas rendering difficulty in morphological diagnosis. P16INK4 is a specific inhibitor of CDK4/CDK6. CDK6 gene is often found co-amplified with MDM2 gene in ALTs. P16 overexpression is a hallmark of cervical dysplasia. Our study investigates the value of p16 expression in cytogenetically confirmed ALTs and deep-seated lipomas. Design: Fifty-one (51) cases of lipomatous neoplasms, with cytogenetic results, from forty-three (43) patients were collected for the study from the archives in department of pathology, UMDNJ/NJMS during 1998 - 2005. These include 18 cases of deep-seated lipoma, one hibernoma, and 32 cases of ALT / well-differentiated liposarcoma (24 patients, five patients with recurrence, and four cases with de-differentiation). Immunohistochemical staining for p16 was performed on representative paraffin blocks. Staining results were scored according to intensity (negative 0, weak 1+, intermediate 2+, and strong 3+) and percentage of positive cells. Results: Twenty-eight cases (28/32, 87.5%) of ALT/WD liposarcoma, including all four cases of dedifferentiated liposarcoma, showed strong nuclear p16 expression. In cases of recurrence, the primary and recurrent tumor showed the same pattern of p16 staining. Four cases (4/32, 12.5%) of ALT/WD liposarcoma showed negative p16 expression. All cases of deep-seated lipoma (18/18, 100%) and single hibernoma showed negative p16 staining except focal positivity in areas of fat necrosis in two cases (p16 positivity, 87.5 vs. 0%, P <0.00001, Fisher's exact test). Conclusion: 1). P16 appears to be a valuable marker to differentiate ALT and deep-seated lipomas. 2). P16 expression remains unchanged in progression and transformation of ALT. 3). P16 related signal transduction pathway most likely is an early event in tumorogenesis of ALT. No significant financial relationships to disclose.