Immunohistochemical significance of ER alpha, inhibin A, calretinin, and Ki67 expression in granulosa cell ovarian tumors (original) (raw)
Related papers
American Journal of Obstetrics and Gynecology, 1996
OBJECTIVE: Our purpose was to evaluate serum antimüllerian hormone as a marker for granulosa cell tumors. STLIDY DE816N: Serum antimüllerian hormone concentrations were determined in 16 patients with an aclult-type granulosa cell tumor; in female patients with ovarian adenocarcinoma, benign ovarian cysts, or extraovarian cancers; and in normal premenopausal and postmenopausal women. Serum antimüllerian hormone, «-inhibin, and estradiol levels were compared in 10 patients with a granulosa cell tumor dudng 6 to 47 months of follow-up. RESULT$: Serum antimüllerian hormone was undetectable in normal postmenopausal women and was <5 gg/L in premenopausal women. Normal serum levels were found in patients with ovarian cancers or cysts or with extraovarian cancers. Levels were between 6.8 and 117.9 gg/L in eight of nine patients with a progressive granulosa cell tumor. In the remaining case antimüllerian hormone, c~-inhibin and estradiol concentrations were normal. Serum antimüllerian hormone and c~-inhibin levels became elevated at least 11 months before the recurrence was clinically detectable. During clinical remission serum antimüllerian hormone, c~-inhibin, and estradiol were normal in most cases. 6ONCLLI$1ON" Serum antimüllerian hormone is a sensitive, specific, reliable marker of adult-type granulosa cell tumors and is useful to evaluate the efficacy of treatment and to detect recurrences early. (AM J OBSTET GYNECOL 1996;174:958-65.) Granulosa cell tumors belong to a category of relatively rare ovarian neoplasms, the sex cord stromal tumors. They represent 1% to 2% of all ovarian tumors 1 but account for 6% to 10% of malignant tumors of the ovary. 2 These tumors are subdivided into two types: the adult form, which represents 95% of all grannlosa cell tumors and has a peak age incidence between 45 and 55 years, and the juvenile form, which usually occurs within the first 3 decades. 1 The primary clinical prognostic factors are stage of disease, tumor size, and tumor rupture dur-
Modern Pathology, 2003
Because ovarian sex cord-stromal tumors (SCST) are morphologically heterogeneous neoplasms that are relatively infrequently encountered, their diagnosis can be difficult. Immunohistochemical staining may be useful for establishing the diagnosis in problematic cases. We studied 53 ovarian SCSTs to characterize their immunohistochemical staining pattern: 17 adult granulosa cell tumors (AGCTs), 4 juvenile granulosa cell tumors (JGCTs), 3 sex cord tumors with annular tubules (SCTATs), 9 Sertoli-Leydig cell tumors (SLCTs), 10 fibromas, 5 fibrothecomas (FTs), and 5 thecomas. In 8 of the 53 cases, the tissue studied was from a metastatic site. The immunopanel included calretinin, inhibin, WT1, cytokeratin cocktail, epithelial membrane antigen (EMA), and cytokeratin 5/6 (CK5/6). The fibromas and FTs were also tested with CD10. The extent of staining was assessed in a semiquantitative fashion and ranked on a scale of 0 through 4؉. All of the tumors, except for 1 metastatic SLCT, were positive for calretinin. Forty-five of the cases (85%) stained for inhibin; 1 metastatic AGCT, 3 fibromas, and 4 FTs were negative. WT1 was present in 39 tumors (74%), with expression most prominent in the SLCTs. The cytokeratin cocktail stained 23 of the 53 tumors (43%), whereas just 1 tumor was positive for EMA (1؉ in a JGCT). All tumors were negative for CK5/6, and the 15 fibromas and FTs were negative for CD10. We conclude that because cytokeratin is frequently expressed by SCSTs, in particular by granulosa cell tumors, SLCTs, and SCTATs, the inclusion of EMA in a panel may help to exclude epithelial neoplasms. In addition, WT1, present in normal granulosa cells, is expressed by a majority of SCSTs. Finally, these results demonstrate that calretinin is at least as sensitive as inhibin for ovarian SCSTs overall and that it is more sensitive than inhibin for fibromas and FTs.
Nuclear Receptor Profiling of Ovarian Granulosa Cell Tumors
Hormones and Cancer, 2011
Granulosa cell tumors of the ovary (GCT) represent~5% of malignant ovarian tumors. The adult form is defined by a mutation in the FOXL2 gene. GCT exhibit many of the features of normal proliferating granulosa cells. We have profiled the expression of the 48 human nuclear receptors (NR) by quantitative RT-PCR in a panel of GCT and in two GCT-derived cell lines, COV434 and KGN. The highest level of expression is seen for COUP-TF2 with abundant expression of PPARγ, SF-1, and TR-α. Estrogen receptor (ER)-β is the most abundant of the steroid receptors with relatively high expression also of AR, ER-α, and PR. The concordance of expression for each NR across the tumors is remarkably high with same discordance between the cell lines and the tumors, particularly the COV434 line. No significant differences were observed with respect to tumor stage for NR expression. These findings provide a full profile of NR expression in GCT which will enable full characterization of their roles and potential as therapeutic targets.
Journal of International Medical Research
Ovarian adult-type granulosa cell tumors are often associated with endometrial hyperplasia or even uterine cancer. Herein, we present a case report of a 65-year-old female patient who had undergone curettage of the uterine cavity several times due to abnormal and irregular uterine bleeding. Owing to recurrent episodes of vaginal bleeding as well as ineffective pharmacological treatment of simple endometrial hyperplasia without atypia, the patient underwent a laparoscopically-assisted vaginal hysterectomy. Owing to an enlarged right ovary with bluish color, intra-operative pathological examination was immediately performed. Surprisingly, an ovarian adult-type granulosa cell tumor was diagnosed, and the surgery was extended to pelvic lymphadenectomy and omentectomy. Immunohistochemical staining with selected antibodies (Arginase 2, Nidogen 2, BAF250a/ARID1A, GPR30, SF-1/NR5A, and 1LRH-2E1/NR5A2) was also performed. In conclusion, in cases of recurrent vaginal bleeding concomitant with...
Human pathology, 2005
Calretinin has been proposed as a novel marker of ovarian sex cord-stromal tumors (SCST); this study aims to determine whether calretinin can complement or supplant the established utility of inhibin in the differential diagnosis of SCST. WT1 has been shown to be expressed in ovarian serous, but not mucinous neoplasms; its expression in a variety of ovarian tumors is also examined. Formalin-fixed, paraffin-embedded archival tissues from 111 primary ovarian tumors were analyzed with commercially available antibodies using semi-automated immunohistochemistry. Results were graded on a 4-tiered scale with staining of more than 0 but less than 5% of cells considered focal. Of 27 SCST, 56% were calretinin and 56% inhibin positive overall; 90% of granulosa cell tumors, 57% of Sertoli-Leydig cell tumors, 33% of thecomas, and 14% of fibromas were calretinin positive. Inhibin was expressed in 60% of granulosa cell tumors, 71% of Sertoli-Leydig cell tumors, 43% of fibromas, and 33% of thecomas...
International Journal of Gynecological Pathology, 2007
Granulosa cell tumor (GCT) is a rare neoplasm hallmarked by a very indolent course and late recurrences. Although numerous clinical and pathological parameters have been implicated as prognostic factors for GCT, their role remains controversial. We performed a retrospective study at our institution where we identified 48 patients with GCT from our tumor registry. Demographic and clinical course information was recorded from the medical record. Twenty of 48 formalin-fixed, paraffin-embedded blocks were retrieved from archived specimens. Pathological parameters such as nuclear atypia, mitotic count, Ki-67 index using immunohistochemistry, and quantitative DNA ploidy were performed. DNA aneuploidy by quantitative method was associated with patients' overall survival. The degree of nuclear atypia, mitotic count, Ki-67 index, and DNA aneuploidy was not predictive of tumor recurrence. Multiinstitutional collaboration is imperative to create a comprehensive national database for investigation into ways that may better indicate prognosis in these patients.
Adult Granulosa Cell Tumor of the Ovary: Initial Evaluation and Current Treatment Paradigm
Adult granulosa cell tumor (AGCT) is a sex cord stromal tumor (SCST) which constitutes 2-5% of all ovarian cancers. Initial treatment of early stage disease includes primary surgical resection with or without adjuvant treatment. Late stage disease and recurrent disease management involves multimodality treatment with surgical resection as the mainstay. Given the rarity of this tumor and its relative chemoresistance, future study is needed to better guide adjuvant treatment and individualize therapy for patients. Further evaluation of diagnostic and potential therapeutic implications involving FOXL2 mutations in AGCT is warranted. 1. Epidemiology/Prognostic Factors Adult granulosa cell tumor (AGCT) is a sex cord stromal tumor (SCST) which constitutes 2-5% of all ovarian cancers and approximately 70% of malignant SCSTs [1]. Despite late recurrences occurring up to 37 years after initial diagnosis, patients typically have a good prognosis since tumors tend to follow an indolent course [2]. Most AGCTs present at an earlier stage compared to epithelial tumors, often with signs of estrogen excess as they express aromatase activity and promote estrogen synthesis [3]. Symptoms include virilization, abnormal uterine bleeding, abdominal distention or pain due to the tumor size, and ascites in 1-2% of the cases [4, 5].
Diagnostic cytopathology, 2016
Granulosa cell tumors (GCT) of the ovary are low grade tumor with a potential ability of late pelvic recurrences and distant metastases. However, there is sparse literature on the cytopathologic features of metastatic granulosa cell tumors (MGCT). Between 2000 and 2014, eight cases of MGCT were diagnosed by FNA. Clinical, cytologic, and histopathologic features were reviewed. The age ranged from 34 to 84 years. Metastases were found in abdominal wall (4 cases), pelvic mass (1 case), liver (2 cases), and lung (1 case). The time to metastasis ranged from 1 to 14 years. All cases were hypercellular, with both large and small overlapping cell clusters and individual cells. The cytologic features included: naked nuclei (8/8 cases), Call-Exner bodies (2/8 cases), and prominent metachromatic stroma (3/8 cases). Moderate cytoplasm (4/8 cases) to scant delicate cytoplasm (4/8 cases) was seen. Cytoplasmic vacuoles were also noted (6/8 cases). N/C ratios were high although lower than small rou...
Predictors of Recurrence of Ovarian Granulosa Cell Tumors
International Journal of Gynecological Cancer, 2009
The prognosis of granulosa cell tumors (GCTs) is overall favorable, but a proportion of patients will experience recurrence. We report one of the largest series of patients with GCT for whom clinical, morphologic, and immunohistochemical markers have been assessed for their roles as predictors of recurrence. Methods: Patients with the diagnosis of GCT were identified at 2 hospitals from 1974 to 2004; a detailed chart analysis was performed. Tissue blocks were analyzed immunohistochemically for mitotic index, luteinization, inhibin staining, epidermal growth factor receptor, and Ki67 expression. Univariate and multivariate analyses were performed. Results: Sixty-seven patients were identified. Follow-up data up to 30 years were available. The mean age at diagnosis was 48.1 years. Twenty-five patients experienced recurrence. A statistically significant correlation (P G 0.05) was observed for age at diagnosis, with earlier age being an adverse factor (43.6 vs 50.9, P G 0.01), and use of adjuvant chemotherapy postoperatively (24% vs 40% in the nonrecurrence group). Luteinization and the immunohistochemical markers, such as inhibin, Ki67, and epidermal growth factor receptor, seemed to significantly increase the risk of recurrence if expressed. A multivariate analysis model confirmed that younger age at diagnosis and higher expression of inhibin and Ki67 are significant risk factors of GCT recurrence. Conclusions: Identification of patients who are at a high risk for recurrence of GCT is critical. Routine treatment for all patients with cytotoxic chemotherapy is not justified. We report a set of predictors of recurrence for GCT that identified subsets of patients who may benefit from prolonged surveillance and/or adjuvant systemic chemotherapy.