Folate receptor alpha expression is widely observed in uterine and ovarian carcinosarcoma (209)

Abstract

<b>Objectives:</b> Folate receptor alpha (FRα) expression has been observed in various cancers, including endometrial, ovarian, lung, and triple-negative breast cancers. FRα is an intriguing therapeutic target, and its expression and clinical significance in uterine and ovarian carcinosarcoma remain to be elucidated. <b>Methods:</b> This retrospective study included patients with gynecologic carcinosarcoma who underwent primary surgery at our institution between 1997 and 2019. Immunohistochemical staining of one representative section of the surgical formalin-fixed paraffin-embedded tissue specimens for FRα was performed using an anti-folate-binding protein/FBP antibody (1:200, ab67422; Abcam, Cambridge, UK). The H-score for FR expression was calculated as follows: 3X+2Y+Z, where X, Y, and Z were the proportions of tumor cells showing strong (3+), moderate (2+), and weak (1+) staining intensities, respectively. FRα-positive staining was defined as more than 5% tumor staining of any intensity and FRα-high as an H-score greater than 50. The association between FRα-high expression and clinical-pathologic features or survival was assessed. <b>Results:</b> Overall, 122 patients with uterine carcinosarcoma and seven patients with ovarian carcinosarcoma were included. In uterine carcinosarcoma, the median age was 62 years (range: 34-87). FIGO (2008) stage distribution was 49, 7, 39, and 26 patients in stage I, II, III, and IV, respectively. FRα expression was observed in all patients, and the median H-score was 50 (range: 10-170). FRα-high showed no significant correlation with age, FIGO stage, a predominant histologic subtype of carcinomatous component, or heterologous sarcomatous elements. During follow-up (median: 30.6 months, range: 0.7-216), 57 patients experienced disease recurrence or died, and 29 patients received palliative chemotherapy. FRα-high was not significantly associated with disease-free survival (HR: 1.16, 95% CI: 0.68-1.98, p=0.58) and overall survival (HR: 1.27, 95% CI: 0.74-2.20, p=0.38), respectively. There was no significant difference in the overall response rate to chemotherapy by FRα-high status. In ovarian carcinosarcoma, all tumor specimens showed FRα expression, and the median H-score was 45 (range: 10-70). The median age was 64 years (range: 55-88), and four patients had FIGO (2008) stage III or IV (57%). <b>Conclusions:</b> FRα expression was observed in all patients with uterine and ovarian carcinosarcoma, but the level of expression was lower than those previously reported in endometrial and ovarian cancers. In uterine carcinosarcoma, there was no significant relationship between FRα overexpression and clinical-pathologic features or prognosis. This widespread FRα expression may provide insights into the development of FRα-targeted therapies for gynecologic carcinosarcoma.