MDM2 and CDK4 Coexpression Is Uncommon in Sarcomatoid Carcinomas
Aoi Sukeda, Akihiko Yoshida, Masayuki Yoshida, Koji Tsuta, Ryoji Kushima, Hitoshi Tsuda. National Cancer Center Hospital, Tokyo, Japan
Background: Most dedifferentiated liposarcomas (DDLPSs) (∼90%) are characterized by the coexpression of MDM2 and CDK4, reflecting the coamplification of the encoding genes. This immunoprofile is rarely seen in other high-grade pleomorphic sarcomas (< 5%), and therefore, it has been suggested to be useful for diagnosing DDLPS. Sarcomatoid carcinomas (SCs) may be difficult to distinguish from true sarcomas because the carcinomatous component may be unsampled and the sarcomatoid element may lack keratin expression. Because SCs often arise from organs in the internal trunk, which is also the favored site for DDLPSs, distinguishing DDLPS from SC can become a diagnostic challenge. However, MDM2 and CDK4 status in SC has not been previously examined, and it is unknown if these markers can help distinguish DDLPS from SC.
Design: We examined 73 SCs arising from various organs in the internal trunk. The tumors tested were, according to the WHO terminology, spindle cell carcinomas of the esophagus (n = 22), carcinosarcoma of the stomach (n = 1), pleomorphic carcinomas of the lung (n = 21), carcinosarcomas of the uterus (n = 24) and ovary (n = 2), and carcinomas with sarcomatoid change of the kidney (n = 3). For each case, immunostaining was performed with antibodies against MDM2 and CDK4. Only the sarcomatoid element was subjected to evaluation. The staining was considered positive when ≥ 1% of tumor cell nuclei were labeled. The results were expressed in terms of intensity (weak or strong) and extent (focal, 1%−10% or diffuse, > 10%).
Results: MDM2 expression was observed in 5/22 (23%) esophageal, 0/1 (0%) gastric, 1/21 (5%) pulmonary, 6/24 (25%) uterine, 0/2 (0%) ovarian, and 2/3 (67%) renal SCs. CDK4 expression was present in 3/22 (14%) esophageal, 0/1 (0%) gastric, 0/21 (0%) pulmonary, 10/24 (42%) uterine, 0/2 (0%) ovarian, and 0/3 (0%) renal SCs. These 2 markers were coexpressed in only 6 (8%) of the 73 cases: 2/22 (9%) esophageal and 4/24 (17%) uterine tumors. In most cases with coexpression, weak or focal reactivity was noted, and none of the cases showed strong diffuse coexpression.
Conclusions: Coexpression of MDM2 and CDK4 in SCs was uncommon (8%), most often, with weak or focal reactivity. These findings are in contrast with those of most DDLPSs that typically exhibit diffuse strong coexpression. Thus, the combination of these 2 markers is likely helpful for distinguishing DDLPS from SC, particularly when the specimen size is limited and conventional epithelial markers produce equivocal results. Ongoing FISH analysis is expected to clarify whether immunoreactivity in SCs reflects underlying gene amplification.
Category: Bone & Soft Tissue
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 26, Tuesday Afternoon