The ARID1A, p53 and ß-Catenin statuses are strong prognosticators in clear cell and endometrioid carcinoma of the ovary and the endometrium

Abstract

Aim: The objective of this study was to evaluate the prognostic value of ARID1A, p53, p21, p16 and ß-Catenin in endometrioid and clear cell ovarian and endometrial carcinomas.

Materials and methods: 97 tumors were available for analysis of ARID1A, p53, p21, p16 and ß-Catenin with the techniques of tissue microarray and immunohistochemistry. 32 were ovarian carcinomas and 65 were endometrial carcinomas.

Results: Endometrioid ovarian carcinomas showed negative staining for ARID1A (a) and p21 (b), aberrant expression of p53 (c) and p16 (d) and ß-Catenin positive nuclear expression (e) respectively in 19% (a), 100% (b), 28.6% (c), 52.4% (d) and 4.8% (e) of all cases. In the group of clear cell ovarian carcinomas it was 63.6% (a), 100% (b), 81.8% (c), 54.5% (d) and 0% (e). For endometrioid uterine carcinomas it was 75.7% (a), 94.9% (b), 30.5% (c), 52.1% (d) and 6.8% (e) and for clear cell uterine carcinomas it was 8.6% (a), 100% (b), 50% (c), 100% (d) and 0% (e). Survival analysis showed that negative expression of ARID1A, p53 aberrant expression and ß-Catenin nuclear positive staining are independent negative prognosticators in both, clear cell and endometrioid carcinoma, regardless of ovarian or uterine origin. Cox-Regression analysis showed them again as negative prognostic factors. Furthermore, we found a significant correlation between ARID1A and ß-Catenin expression in endometrioid uterine tumors.

Conclusion: The analyzed gynaecological carcinoma showed a distinct expression scheme of proteins that are associated with tumor suppression. We may conclude that ARID1A, p53 and ß-Catenin are the strongest prognostic factors by analyzing a subgroup of tumor suppressor genes in clear cell and endometrioid subtypes of ovarian and endometrial cancer and may be used along with traditional morphological and clinical characteristics for prognosis.

Fig 1

Immunohistochemical stainings for ß-Catenin, p53, ARID1A, p16 and p21 in clear-cell (A and B) and endometrioid (C—K) carcinomas. Focal, very weak membranous (n-m-) (A), membranous (n-m+) (B) and nuclear (n+m+) (C) expression of β-catenin. Regulated (D) and aberrant (E) expression of p53. Preserved expression of ARID1A (F) and loss (G) of ARID1A expression. Negative staining (H) and positive (I) staining for p16. Negative (J) and positive staining (K) of p21. 400 × magnification was used for all pictures; scale bar (K) refers to 60 μm for all images.

Fig 2. Survival analysis for ARID1A.

Survival was better for the subgroup of patients with ARID1A positive tumors (N = 27) compared to the subgroup with ARID1A negative tumors (N = 70).

Fig 3. Survival analysis for p53.

Survival was better for the subgroup of patients with p53 positive tumors (N = 61) compared to the subgroup with p53 negative/overexpression tumors (N = 36).

Fig 4. Survival analysis for ß-Catenin.

Survival analysis for ß-Catenin. Survival was better for the subgroup of patients with ß-Catenin n-m+ tumors (N = 64) compared to the subgroup ß-Catenin n-m- (N = 28) and ß-Catenin n+m+ tumors (N = 5).