Immunohistochemistry with apoptotic-antiapoptotic proteins (p53, p21, bax, bcl-2), c-kit, telomerase, and metallothionein as a diagnostic aid in benign, borderline, and malignant serous and mucinous ovarian tumors

Abstract

Background: In many tumors including ovarian cancer, cell proliferation and apoptosis are important in pathogenesis and there are many alterations in most of the genes related to the cell cycle. This study was designed to evaluate immunohistochemistry with apoptotic-antiapoptotic proteins (p53, p21, bax, and bcl-2), c-kit, telomerase, and metallothionein as a diagnostic aid in typing of benign, borderline, and malignant serous and mucinous ovarian tumors.

Methods: Total of 68 ovarian tumors, 25 benign [13 (19.1%) serous and 12 (17.6%) mucinous], 16 borderline [9 (13.2%) serous and 7(10.3%) mucinous], and 27 malignant ovarian tumors [24 (35.3%) serous and 3 (4.4%) mucinous tumors] were included in the study. Immunohistochemical expression of p53, p21, bax, bcl-2, telomerase, c-kit, and metallothionein were evaluated.

Results: When all 68 cases were evaluated as benign, borderline, and malignant ovarian tumors without considering histopathological subtypes, the p53, p21, bax and metallothionein showed significantly higher staining scores in the borderline and malignant ones (p < 0.05). After evaluation of all 68 cases, the serous tumors showed significantly higher staining scores of p53, p21, c-kit, and metallothionein compared to the mucinous ones (p < 0.05). For differentiation of benign and borderline and malignant tumors combined, p53 was not used because all benign tumors has no staining, and p21, bax, and metallothionein was determined the significant predictors for borderline and malignant tumors combined (p < 0.05). For differentiation of borderline and malignant tumors, only p53 was determined the significant predictor for malignant tumors (p < 0.05).

Conclusions: In conclusion, p53, p21, bax, c-kit, and metallothionein may be helpful for the typing of ovarian tumors as benign, borderline and malignant or serous and mucinous. p53, p21, bax, c-kit, and metallothionein may have different roles in the pathogenesis of ovarian tumor types. p53 and metallothionein may be helpful in the typing of borderline and malignant ovarian tumors. The immunohistochemical staining with bcl-2 and telomerase may not provide meaningful contribution for the typing of ovarian tumors.

Virtual slide: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2013030833768498.

Figure 1

Representative pictures of p53staining in a grade 2 serous carcinoma (a), grade 1 serous carcinoma (b) and mucinous carcinoma (c); p21 staining in a serous carcinoma (d), serous ovarian borderline tumor (e), and mucinous carcinoma (f); bax staining in a serous carcinoma (g), mucinous ovarian borderline tumor (h), and mucinous carcinoma (i); bcl-2 staining in a serous carcinoma (k) and serous ovarian borderline tumor (m). P53 and p21 immunostaining was restricted to the nuclei. Baxlabelling was observed in both the outer of the membrane and the cytoplasm. Bcl-2 immunostaining was detected in the cytoplasm. ([a-h, k-m] IHC; X100 and [i] IHC; X200).

Figure 2

Membranous and cytoplasmic staining for c-kit was depicted in a serous carcinoma (IHC; X100).

Figure 3

Telomerase nuclear staining in a serous carcinoma (a) and mucinous carcinoma (b). (IHC; X200).

Figure 4

Representative pictures of metallothionein staining in a serous carcinoma (a), serous ovarian borderline tumor (b), mucinous ovarian borderline tumor (c), and mucinous carcinoma (d). Metallothionein staining was detected in the cytoplasm and/or membrane. ([a-d] IHC; X100).