Date Published: February 16, 2018
Publisher: Public Library of Science
Author(s): Marlene Heckl, Elisa Schmoeckel, Linda Hertlein, Miriam Rottmann, Udo Jeschke, Doris Mayr, Eric Asselin.
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.
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.
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.
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.
The traditional histopathological classification of endometrial epithelial cancer, which was first proposed by Bokhman, includes type I tumors that are usually estrogen-dependent low-grade endometrioid cancers and type II tumors which are usually estrogen-independent high-grade serous or clear cell carcinomas . While the first pathogenetic type has a frequency of 80–90% and is associated with highly or moderately differentiated tumors with a favorable prognosis, the second type has a frequency of only 10–20% and includes poorly differentiated tumors with a doubtful prognosis .
Endometrial cancer can be subdivided into two histological subtypes, the estrogen-associated type I which includes endometrioid carcinomas and the estrogen-independent type II which comprises mostly high-grade serous and clear cell carcinoma . The type II carcinoma is known to metastasize more often and to have a worse survival. A less accepted paradigm for ovarian cancer also differs between type I tumors which include endometrioid, clear cell and low-grade serous carcinoma and type II tumors containing p53-mutated high-grade serous carcinoma .