Prognostic value of immunohistochemical markers in malignant thymic epithelial tumors

Leisibach, Priska; Soltermann, Alex; Yamada, Y.; Weder, Walter; Jungraithmayr, Wolfgang

doi:10.21037/jtd.2016.08.82

Cited by 16 publications

(12 citation statements)

References 36 publications

(67 reference statements)

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“…p21 is phosphorylated by Akt1 and murine leukemia virus (Pim-1) at threonoine-145 in order to keep it in the cytoplasm [1, 71] and cancers with high p21 cytoplasmic/nuclear ratio are thought to be more aggressive. Therefore, our finding that AI-resistant MCF-7:5C cells have very high expression of IFITM1 but very low nuclear p21 expression is consistent with their highly aggressive phenotype both in vitro and in vivo [20, 40, 75]. …”

Section: Discussionmentioning

confidence: 66%

IFITM1 suppression blocks proliferation and invasion of aromatase inhibitor-resistant breast cancer in vivo by JAK/STAT-mediated induction of p21

et al. 2017

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Interferon induced transmembrane protein 1 (IFITM1) belongs to a family of interferon stimulated genes (ISGs) that is associated with tumor progression and DNA damage resistance, however, its role in endocrine resistance is not known. Here, we correlate IFITM1 expression with clinical stage and poor response to endocrine therapy in a tissue microarray consisting of 94 estrogen receptor (ER)-positive breast tumors. IFITM1 overexpression is confirmed in the AI-resistant MCF-7:5C cell line and not found in AI-sensitive MCF-7 cells. In this study, the orthotopic (mammary fat pad) and mouse mammary intraductal (MIND) models of breast cancer are used to assess tumor growth and invasion in vivo. Lentivirus-mediated shRNA knockdown of IFITM1 in AI-resistant MCF-7:5C cells diminished tumor growth and invasion and induced cell death, whereas, overexpression of IFITM1 in wild-type MCF-7 cells promoted estrogen-independent growth and enhanced their aggressive phenotype. Mechanistic studies indicated that loss of IFITM1 in MCF-7:5C cells markedly increased p21 transcription, expression and nuclear localization which was mediated by JAK/STAT activation. These findings suggest IFITM1 overexpression contributes to breast cancer progression and that targeting IFITM1 may be therapeutically beneficial to patients with endocrine-resistant disease.

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Section: Discussionmentioning

confidence: 66%

IFITM1 suppression blocks proliferation and invasion of aromatase inhibitor-resistant breast cancer in vivo by JAK/STAT-mediated induction of p21

et al. 2017

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“…These tumors represent a distinct histologic subtype of thymic carcinoma which is characterized by highly atypical tumor cells that grow in cords, nests, and trabeculae and often contain a dense lymphoplasmacytic infiltrate in the stroma [4]. Recently, several studies have identified increased expression of PD-L1 and PD-1 in thymic epithelial neoplasms including thymomas and thymic carcinomas suggesting that these lesions may be responsive to PD-L1/PD-1 inhibitor therapy [5][6][7][8][9][10][11][12][13][14]. However, the expression of PDL-1 in lymphoepithelioma-like carcinoma of the thymus has not yet been specifically addressed.…”

Section: Introductionmentioning

confidence: 99%

Expression of PD-L1/PD-1 in lymphoepithelioma-like carcinoma of the thymus

et al. 2018

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Poorly differentiated non-keratinizing squamous cell carcinoma of the thymus, also known as lymphoepithelioma-like carcinoma, is a rare primary malignant neoplasm of thymic origin. The mainstay of treatment for these tumors is surgical and they tend to respond poorly to chemotherapy. The checkpoint programmed cell death ligand-1 protein (PD-L1) bound to its receptor (PD-1) has been demonstrated to be an important therapeutic target for many different tumors. Expression of PD-L1/PD-1 in lymphoepithelioma-like carcinoma of the thymus may indicate that these tumors are potential targets for inhibitor therapy. Twenty-one cases of lymphoepithelioma-like carcinoma of the thymus were collected and reviewed. Tissue microarrays were created using triplicate 2 mm cores for each case. PD-L1/PD-1 staining pattern (neoplastic cells versus tumor infiltrating lymphocytes) was documented for each case. Out of 21 cases, 15 (71.4%) showed various degrees of membranous PD-L1 staining. Of the positive cases, 48% showed high expression of PD-L1 (>50% of tumor cells) and 24% showed low expression (<50%). PD-1 staining showed focal positivity in 12/20 (60%) cases among tumor infiltrating lymphocytes. PD-L1/PD-1 inhibitor therapy has been applied successfully in other solid malignant tumors with high expression of PD-L1/PD-1. The high level of PD-L1 expression in our cases indicates that PD-L1 may play a role in the pathogenesis of these tumors and that PD-L1/PD-1 blockade may be a viable therapeutic option for patients with lymphoepithelioma-like carcinoma of the thymus who have failed other first-line therapies.

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“…Fine-needle aspiration cytology and core needle biopsies are the gold standard in the primary diagnosis of patients with breast neoplasms to observe changes in morphology. Immunohistochemical markers can confirm changes observed by hematoxylin & eosin staining [16]. On balance, the disease should be detected, diagnosed, and treated early.…”

Section: Discussionmentioning

confidence: 98%

A Clinical Observation of Thymic Epithelial Tumor Metastatic to Breast

Deng¹,

Li²,

Wu³

et al. 2018

Breast Care

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Background: Thymic carcinoma is prone to early metastasis and invasion, while its metastasis to the breast is particularly unique. Case Report: We describe a case of thymic epithelial tumor metastatic to the breast fulfilling clinical diagnostic criteria. A 47-year-old female patient diagnosed with stage IV thymic carcinoma and previously treated with chemoradiation was diagnosed with metastatic breast cancer during a periodic review. Color Doppler ultrasonography showed a low-echo real occupancy in the breast. Pathological examination of the breast mass confirmed the diagnosis of thymic carcinoma metastasis. Conclusion: Hematogenous metastasis of thymic carcinoma to the breast is rare but not exceptional, and long-term survival can be expected with appropriate treatment.

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Prognostic value of immunohistochemical markers in malignant thymic epithelial tumors

Cited by 16 publications

References 36 publications

IFITM1 suppression blocks proliferation and invasion of aromatase inhibitor-resistant breast cancer in vivo by JAK/STAT-mediated induction of p21

IFITM1 suppression blocks proliferation and invasion of aromatase inhibitor-resistant breast cancer in vivo by JAK/STAT-mediated induction of p21

Expression of PD-L1/PD-1 in lymphoepithelioma-like carcinoma of the thymus

A Clinical Observation of Thymic Epithelial Tumor Metastatic to Breast

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