Regular article
Clinicopathological analysis of c-kit expression in carcinosarcomas and leiomyosarcomas of the uterine corpus

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Abstract

Objective

The purpose of this study was to evaluate the expression of the protooncogene, c-kit, in carcinosarcomas and leiomyosarcomas of the uterine corpus and determine the associations between c-kit expression and clinicopathologic factors, including clinical outcome.

Methods and materials

Using a polyclonal anti-KIT-antibody, immunohistochemical staining was performed on formalin-fixed paraffin-embedded tissue blocks from 21 carcinosarcomas, 17 leiomyosarcomas, and 1 endometrial stromal sarcoma. KIT-positive tumors were defined as those tumors demonstrating immunopositivity in ≥30% of tumor cells examined. KIT-negative lesions demonstrated immunopositivity in <30% of tumor cells. Two authors independently scored the slides as positive or negative. Staining was repeated on all specimens and independently scored, and in the occasion of a mismatch, a third staining was performed. The carcinosarcomas were catalogued as to whether the sarcomatous and/or carcinomatous elements expressed c-kit. Clinical data were abstracted for those patients with uterine carcinosarcomas. The associations between clinicopathologic characteristics and c-kit expression were compared using univariate and multivariate analyses. Kaplan-Meier curves based on c-kit expression were plotted for progression-free and overall survival and compared using the log-rank test.

Results

Nine of 21 (43%) carcinosarcomas demonstrated immunopositivity for the KIT receptor, although staining was relatively weak. In contrast, only 1/17 (6%) leiomyosarcomas demonstrated KIT immunopositivity (P = 0.029). The solitary endometrial stromal sarcoma evaluated did not demonstrate significant KIT positivity. The majority of KIT-positive carcinosarcomas (6/9 (67%)) demonstrated KIT presence in the sarcomatous portion as compared to the carcinomatous portion (4/9 (44%)). No clinical factor had a statistically significant association with c-kit expression. The lack of c-kit expression was the only factor that was significantly associated with disease recurrence in univariate and multivariate analyses (P < 0.05), although there appeared to be a trend toward a low stage associated with kit positivity. The median progression-free interval for the KIT-negative cohort was 8 months, while it had not been reached for the KIT-positive cohort after median follow-up of 15 months (P = 0.0462).

Conclusions

A significant proportion of carcinosarcomas of the uterine corpus display immunoreactivity for c-kit. Patients with KIT-positive carcinosarcomas may have an improved progression-free survival compared to KIT-negative tumors; however, further data are needed to determine whether this finding is confounded by stage.

Section snippets

Tissue specimens

Tumor specimens were collected for all patients at Walter Reed Army Medical Center and Washington Hospital Center (Washington, DC) with a histologic diagnosis of uterine carcinosarcoma (1993–2001), leiomyosarcoma (1985–1994), or endometrial stromal sarcoma (1990). Formalin-fixed paraffin-embedded tissue specimens from 39 patients—21 carcinosarcomas, 17 leiomyosarcomas, and 1 endometrial stromal sarcoma—were obtained in accordance with an institutional review board-approved protocol. No

Immunohistochemistry

Immunohistochemical staining of 39 sarcomas of the uterine corpus revealed immunopositivity in 10 specimens (Table 1 and Fig. 1). The majority of KIT-positive sarcomas showed a diffuse staining pattern (6/10 (60%)) as compare to focal staining (4/10 (40%)). Nine of 21 (43%) of the carcinosarcomas demonstrated immunopositivity for the KIT receptor. It is important to note that the intensity of staining in the carcinosarcomas was relatively weak and significantly less than that seen in the

Discussion

Uterine sarcomas represent 2–6% of all uterine malignancies [16]. Although carcinosarcomas have always been grouped with uterine sarcomas, it is important to recognize that recent data support the classification of these tumors as metaplastic carcinomas [17]. In a review of British tumor registries carcinosarcomas and leiomyosarcomas made up almost 90% of all uterine sarcomas registered over a 15-year period [18]. The overall 5-year survival was 31% in this series. Studies evaluating only

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