Clinicopathologic and Immunohistochemical Features of Ovarian Clear Cell Carcinomas in Comparison With Type I and Type II Tumors

Abstract

Two types of ovarian carcinomas are distinguished with respect to morphology, biology, and clinical course, and are designated as Type I and Type II tumors. However, placement of clear cell carcinomas into one of these 2 groups has been problematic as they exhibit morphologic, molecular, and clinical features that do not entirely resemble either Type I or Type II tumors. The present study aimed at better elucidating the clinicopathologic and immunohistochemical features of clear cell carcinomas, in comparison with the 2 main broad categories. To this end, a panel of classic clinicopathologic and immunohistochemical parameters, including estrogen receptor α (ERα), ERβ, progesterone receptor, Ki67, p53, and HER2/neu was evaluated in 71 Type I, 157 Type II, and 21 clear cell carcinomas. Overall, findings from the present study support the idea that ovarian clear cell carcinomas are neither Type I nor Type II carcinomas of the ovary; indeed, results obtained showed that similarities between clear cell carcinomas and Type I were limited to the patient's age, tumor dimension, incidence of lymph node and extranodal metastases, and p53 labeling index, whereas the patient's age and incidence of extranodal metastases were the only parameters comparable with the Type II group. The hormonal receptor profile of clear cell carcinomas was characterized by low expression of nuclear ERα and progesterone receptor, and by almost exclusively nuclear ERβ immunopositivity, features significantly different from both Type I and II tumors. Finally, the percentage of HER2/neu-positive samples in clear cell carcinomas was 10- and 2.5-fold higher than Type I and Type II ovarian tumors, respectively. In conclusion, our study provides insights into clear cell carcinoma that could help in explaining its unique prognostic features, and, eventually, in orienting toward new therapeutic options.

Napsin A as a marker of clear cell ovarian carcinoma

“…This is also in agreement with recent findings from Zannoni et al [4], where they show that clear cell ovarian carcinoma should be studied separately, but still in comparison with the groups of Type I and Type II tumors. In a study from Chan et al [6] it was concluded, that women with clear cell ovarian carcinoma are likely to be younger at diagnosis.…”

“…At present, post-surgical therapy is mainly dependent upon tumor stage and grade rather than histological subtype [2]. On the basis of a series of morphologic and molecular genetic studies various types of ovarian cancer can be classified into two groups designated type I and type II [3,4]. Clear cell carcinoma (CCC), which constitutes 5-6% of ovarian malignancies exhibit morphologic, molecular, and clinical features that do not entirely resemble either Type I or Type II tumors and unlike, other Type I tumors, clear cell carcinoma CCC is high grade at presentation [4,5].…”

Immunohistochemical Comparison of Ovarian and Uterine Endometrioid Carcinoma, Endometrioid Carcinoma With Clear Cell Change, and Clear Cell Carcinoma

“…They are frequently expressed in low-grade to intermediate-grade EC (> 70% tumors) but are usually negative in CCC. 18,[47][48][49][50] However, they may be less useful in the setting of a high-grade EC, as up to two thirds of these tumors can exhibit a loss of expression of 1 or both receptors. 49 Hoang and colleagues examined the immunoexpression patterns of HNF1b and ER in endometrial CCC, EC, and serous carcinomas and observed moderate to strong, diffuse nuclear HNF1b staining and no ER expression in 14/15 CCCs and 1/15 serous carcinomas.…”

Endogenous androgens and risk of epithelial invasive ovarian cancer by tumor characteristics in the European Prospective Investigation into Cancer and Nutrition

“…An incidence density sampling protocol was used, such that controls could include subjects who became a case later in time and each control could be sampled more than once. Cases and controls in both study phases were matched on: study recruitment center, age at blood donation (66 months), time of the day of blood collection (61 h), fasting status (<3 h, 3-6 h, >6 h), and menopausal status at blood collection (premenopausal, perimenopausal, postmenopausal), as well as menstrual cycle phase for premenopausal women ("early follicular" (days 0-7 of the cycle), "late follicular" (days 8-11), "peri-ovulatory" (days 12-16), "mid-luteal" (days [20][21][22][23][24], and "other luteal" (days 17-19 or days [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40]. Cases missing data on phase of menstrual cycle were matched to controls with missing information on menstrual cycle phase.…”