Emerging biomarkers in ovarian granulosa cell tumors

Abstract

ObjectiveAlthough the majority of ovarian granulosa cell tumors can be successfully managed with surgery, a subset require chemotherapy for residual and recurrent disease. The benefit of chemotherapy in this population, however, remains controversial. There is therefore interest in the development of more tolerable and effective treatment options for advanced ovarian granulosa cell tumors. We report the use of immunohistochemistry to investigate how biomarkers could inform clinical trials in granulosa cell tumors with an emphasis on emerging androgen antagonistic, immunotherapeutic, and anti-angiogenic approaches.MethodsImmunohistochemistry for androgen receptor, the immune markers programmed cell death ligand 1, indoleamine-2,3 dioxygenase, and cluster of differentiation 8, and the vascular marker cluster of differentiation 31 were evaluated on formalin-fixed paraffin-embedded whole tissue sections from 29 cases of adult-type granulosa cell tumors. Results were evaluated with clinicopathologic variables including recurrence.Results59% of granulosa cell tumors were androgen receptor-positive, suggesting a potential role for anti-androgen therapy in this tumor type. In contrast, the targetable immune modulatory molecules programmed cell death ligand 1 and indoleamine-2,3 dioxygenase were scarcely expressed, with no cases showing tumorous programmed cell death ligand 1 and a single case demonstrating very focal tumorous indoleamine-2,3 dioxygenase staining. A minority of cases expressed programmed cell death ligand 1 in occasional tumor-associated macrophages and indoleamine-2,3 dioxygenase in peritumoral vessels. Tumor-infiltrating cytotoxic T cells were also scarce in granulosa cell tumors, arguing against a significant role for immunotherapy in the absence of additional immunostimulation. Cluster of differentiation 31 immunostaining revealed a range of vascular densities across granulosa cell tumors, and future studies evaluating the role of vascular density as a predictor of response to angiogenesis inhibition are warranted. None of the biomarkers investigated were significantly correlated with recurrence, and the only clinicopathologic feature significantly correlated with outcome was stage at presentation.ConclusionsBiomarker data suggest that many ovarian granulosa cell tumors could be candidates for anti-androgen therapy, while the potential role for immunotherapy appears more limited. Vascular density could be useful for identifying optimal candidates for angiogenesis inhibition. Incorporation of these biomarkers into clinical trials could help optimize patient selection.

Development of Pathological Super-resolution Images using Artificial Intelligence based on Whole Slide Image

“…Due to its variable histological features and various forms often mixed in the same tumor, this undoubtedly caused some di culties in diagnosis of AGCT. A large number of studies have shown that the Call-Exnar body and coffee bean-like nucleus or longitudinal nucleus are the characteristic changes in typical AGCT, which is an important suggestion for the diagnosis of ovarian adult granulosa cells 10 . Thus, to make the diagnosis more accurate, it is necessary for pathologists to see the details or features of nucleus under x40 magni cation images.…”

Development of pathological reconstructed high‐resolution images using artificial intelligence based on whole slide image

“…8 Histologically, GCTs are divided into adult and juvenile, with the former accounting for 95% of all GCTs. 8 , 9 Although some clinical manifestations such as estrogen stimulation and related hormone levels have an auxiliary role in the diagnosis of this tumor, the final diagnosis still depends on the traditional histopathological examination under light microscopy. Microscopically, tumor cells are arranged in trabecular, island‐like, pseudo‐adenoid, vesicular, or solid lamellae.…”

“…A large number of studies have shown that the Call‐Exnar body and coffee bean‐like nucleus or longitudinal nucleus are the characteristic changes in typical AGCT, which is an important suggestion for the diagnosis of ovarian adult granulosa cells. 9 Thus, for a more accurate diagnosis, it is necessary for pathologists to observe the details or features of the nucleus in × 40 magnification images.…”

[18F]FDG and [18F]FES positron emission tomography for disease monitoring and assessment of anti-hormonal treatment eligibility in granulosa cell tumors of the ovary

“…AGCTs commonly express the estrogen receptors alpha (ERα, 30-66%) and beta (ERβ, 94-100%) [14][15][16][17]. Therefore, anti-hormonal treatment is thought to be a potentially effective treatment strategy.…”