High expression of SALL4 and fascin, and loss of E-cadherin expression in undifferentiated/dedifferentiated carcinomas of the endometrium: An immunohistochemical and clinicopathologic study

Abstract

Undifferentiated/dedifferentiated endometrial carcinomas (UCE/DCEs) of the endometrium are rare tumors with poor prognosis. There are few clinicopathologic studies with detailed immunohistochemical analysis regarding UCE/DCEs.We evaluated the diagnostic value of a selected tumor stem-cell marker and epithelial-mesenchymal transition (EMT) markers, in addition to previously studied markers in identifying UCE/DCEs from other types of high-grade endometrial carcinomas.Eleven cases of UCE/DCEs with complete clinical follow-up that were diagnosed between 2006 and 2015 were included in the study. For immunohistochemical comparison, 11 clinically matched cases for each type of other high-grade endometrial carcinomas (high-grade endometrioid (F3-EC), serous [SC], and clear cell carcinoma [CCC]) were used as a control group. An immunohistochemical analysis including fascin, SALL4, E-cadherin, and β-catenin, in addition to epithelial and neuroendocrine markers was performed in each case.The majority of UCE/DCEs displayed diffuse expression of fascin (81.9%) and loss of E-cadherin expression (54.5%). SALL4 expression was detected in 36.3% of the UCE/DCE cases. SALL4 expression was significantly more frequent in UCE/DCEs than all other high-grade carcinomas (P < 0.001). Loss of E-cadherin and fascin expression was significantly more frequent in UCE/DCEs than high-grade endometrioid and clear cell adenocarcinomas (P = 0.012, 0.014 and P = 0.01, 0.003, respectively).We suggest that loss of E-cadherin expression together with fascin and SALL4 immunopositivity in addition to morphologic features have an impact in differential diagnosis of UCE/DCEs from other high-grade endometrial carcinomas.

Figure 1

(A) Large exophytic and polypoid tumoral lesion filling the entire endometrial cavity and extending to the endocervical region. (B) Microscopically, tumoral cells infiltrating deep myometrium (H&E, ×10, original magnification). (C) The dedifferentiated endometrial carcinoma consisting of well-differentiated endometrioid carcinoma (left side) and undifferentiated carcinoma (right side) (H&E, ×20, original magnification). (D) The neoplastic cells have medium-sized nuclei with vesicular chromatin (H&E, ×100, original magnification).

Figure 2

(A) EMA is also focal positive in neoplastic cells of a case of undifferentiated carcinoma (EMA, ×20, original magnification). (B) The neoplastic cells are focally positive for PanCK (×20, original magnification). (C) The neoplastic cells display patchy staining with Chr A in a case of undifferentiated carcinoma (Chr A, ×20, original magnification). (D) Syn is also focal positive in neoplastic cells in a case of undifferentiated carcinoma (Syn, ×40, original magnification). Chr A = chromogranin A, EMA = epithelial membrane antigen, PanCK = pancytokeratin, Syn = synaptophysin.

Figure 3

(A, B) Positive immunostaining for fascin in an undifferentiated (A) and serous adenocarcinoma (B) (Fascin, ×40, original magnification). (C) Loss of immunostaining of E-cadherin in undifferentiated component and diffuse immunostaining in differentiated component in a dedifferentiated carcinoma (E-cadherin, ×20, original magnification). (D, E) Punctate staining in an undifferentiated carcinoma (D) and cytoplasmic staining in endometrioid adenocarcinoma (E) (β-catenin, ×40, original magnification). (F) Positive immunostaining in an undifferentiated carcinoma (SALL4, ×40, original magnification).