Immunohistochemistry expression of targeted therapies biomarkers in ovarian clear cell and endometrioid carcinomas (type I) and endometriosis

Barreta, Amilcar; Sarian, Luís Otávio; Ferracini, Amanda Canato; Costa, Larissa Bastos Eloy da; Mazzola, Priscila Gava; Andrade, L; Derchain, Sophie

doi:10.1016/j.humpath.2018.10.028

Cited by 18 publications

(12 citation statements)

References 26 publications

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“…The expression of VEGF, an angiogenic factor, is significantly elevated in EAOC compared with endometriosis [ 84 ] and is reported to be expressed in more than 90% of OCCC cases [ 85 ]. Anti-VEGF antibodies, which are angiogenesis inhibitors, have already been used for ovarian cancer, including EAOC [ 86 , 87 , 88 , 89 , 90 ].…”

Section: Landscape Of Targeted Therapy and Immunotherapy For Eaocmentioning

confidence: 99%

Endometriosis-Associated Ovarian Cancer: The Origin and Targeted Therapy

Murakami

Kotani

Nakai

et al. 2020

Cancers

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Endometrial cysts (ECs) are thought to be the origin of endometriosis-associated ovarian cancer (EAOC). A hypothesis that the oxidative stress of iron in cysts causes “malignant transformation of ECs” has been proposed, but this has not been verified. Several population-based studies showed that endometriosis was a risk factor but did not reflect the “malignant transformation of ECs”. A review showed that most patients were diagnosed with EAOC early in monitoring following detection of ECs, and that these cases might have been cancer from the start. Epidemiologically, EAOC was reduced by hysterectomy rather than by cystectomy of ECs. Gene mutation analyses identified oncogenic mutations in endometriosis and normal endometrium and revealed that the same mutations were present at different endometriotic lesions. It was also shown that most of the gene mutations found in endometriosis occurred in normal endometrium. Taking together, EAOC might be caused by eutopic endometrial glandular epithelial cells with oncogenic mutations that have undergone menstrual blood reflux and engrafted in the ovary, rather than by low-risk ECs acquiring oncogenic mutations and becoming malignant. This review discusses the mechanisms of EAOC development and targeted therapy based on genetic variation in EAOC with a focus on eutopic endometrium.

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Section: Landscape Of Targeted Therapy and Immunotherapy For Eaocmentioning

confidence: 99%

Endometriosis-Associated Ovarian Cancer: The Origin and Targeted Therapy

Murakami

Kotani

Nakai

et al. 2020

Cancers

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“…Subsequently, the stained cell ratio score and the staining intensity score were multiplied by each other to obtain a final score for each of the fields that were analyzed. A score average ranging between 0 and 3 was calculated for comparison analysis ( Table S1 ) [ 17 , 18 ].…”

Section: Methodsmentioning

confidence: 99%

High Expression of SOD2 Protein Is a Strong Prognostic Factor for Stage IIIB Squamous Cell Cervical Carcinoma

et al. 2021

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High superoxide dismutase 2 (SOD2) expression is associated with a poor prognosis at many cancer sites, the presence of metastases, and more advanced cervical cancer. This study aims to determine whether SOD2 protein expression is associated with the prognosis of stage IIIB cervical carcinoma. Methods: sixty-three patients with stage IIIB squamous cell cervical carcinoma were included. The evaluation of SOD2 expression by immunohistochemistry was based on a positive cell ratio score and the staining intensity score. Taking disease recurrence and death as endpoints, receiver operating characteristic curves were used to discriminate between high and low SOD2 expression. Results: high SOD2 expression was associated with recurrence (p = 0.001), distant recurrence (p = 0.002), and death (p = 0.005). A multivariate analysis showed that patients with high SOD2 expression had a threefold increased risk for recurrence (HR = 3.16; 1.33–7.51) and death (HR = 2.98; 1.20–7.40) compared with patients who had low SOD2 expression. Patients with high SOD2 expression had shorter disease-free survival (p = 0.001) and overall survival (p = 0.003) than patients with low SOD2 expression. Conclusion: high SOD2 expression is a strong prognostic factor for stage IIIB squamous cell carcinoma of the cervix and could be used as a prognostic marker in women with cervical carcinoma.

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“…Figure 3a summarizes the frequencies of ARID1A mutations and loss of BAF250A/ ARID1A protein expression in OCCC in studies to date [12,13,[32][33][34][35][36][37]. In particular, many immunohistochemical studies to examine loss of BAF250A expression in OCCC tissues have been performed [38][39][40]. Loss of BAF250A, reflected by lack of nuclear staining for this protein, is observed frequently in OCCC cells.…”

Section: Arid1a and Other Swi/snf Gene Alterations In Occcmentioning

confidence: 99%

Treatment Strategies for ARID1A-Deficient Ovarian Clear Cell Carcinoma

Takahashi

Takenaka

Okamoto

et al. 2021

Cancers

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Ovarian clear cell carcinoma (OCCC) is a histological subtype of ovarian cancer that is more frequent in Asian countries (~25% of ovarian cancers) than in US/European countries (less than 10%). OCCC is refractory to conventional platinum-based chemotherapy, which is effective against high-grade serous carcinoma (HGSC), a major histological subtype of ovarian cancer. Notably, deleterious mutations in SWI/SNF chromatin remodeling genes, such as ARID1A, are common in OCCC but rare in HGSC. Because this complex regulates multiple cellular processes, including transcription and DNA repair, molecularly targeted therapies that exploit the consequences of SWI/SNF deficiency may have clinical efficacy against OCCC. Three such strategies have been proposed to date: prioritizing a gemcitabine-based chemotherapeutic regimen, synthetic lethal therapy targeting vulnerabilities conferred by SWI/SNF deficiency, and immune checkpoint blockade therapy that exploits the high mutational burden of ARID1A-deficient tumor. Thus, ARID1A deficiency has potential as a biomarker for precision medicine of ovarian cancer.

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Immunohistochemistry expression of targeted therapies biomarkers in ovarian clear cell and endometrioid carcinomas (type I) and endometriosis

Cited by 18 publications

References 26 publications

Endometriosis-Associated Ovarian Cancer: The Origin and Targeted Therapy

Endometriosis-Associated Ovarian Cancer: The Origin and Targeted Therapy

High Expression of SOD2 Protein Is a Strong Prognostic Factor for Stage IIIB Squamous Cell Cervical Carcinoma

Treatment Strategies for ARID1A-Deficient Ovarian Clear Cell Carcinoma

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