Ephrin Receptors (Ephs) Expression in Thymic Epithelial Tumors: Prognostic Implications and Future Therapeutic Approaches

Ephrin receptors (Ephs) are receptor tyrosine kinases (RTKs) implicated in tissue development and homeostasis, and they are aberrantly expressed in tumors. Here, immunohistochemical Eph type-A and -B expression in thymic epithelial tumors (TETs) was assessed and correlated with clinicopathological parameters. Tissue microarrays from 98 TETs were stained for EphA1, -A2, -A4 -A6, -B1, -B2, -B4 and -B6. The relationship between neoplastic and lymphoid cell immunoreactivity score (H-score), histopathological parameters (Pearson’s test) and survival of 35 patients (Mantel-Cox model) was explored. Epithelial-rich subtypes showed higher EphA6 cytoplasmic H-score (B2/B3, carcinoma) (p < 0.001) and stronger EphA4 H-score (B3, carcinoma) (p = 0.011). The immature T-cells, especially in subtypes AB/B1, had higher EphB6 H-score than carcinoma-associated mature lymphocytes (p < 0.001); carcinomas had higher lymphocytic EphB1 H-score (p = 0.026). Higher lymphocytic and lower epithelial EphB6 H-score correlated with Masaoka stage ≤II (p = 0.043, p = 0.010, respectively). All cases showed variable epithelial and lymphocytic EphA2 expression, but clinicopathological associations were not reached. Our study confirmed that Eph type-A and -B expression in TETs is associated with established prognostic parameters, i.e., tumor subtype and Masaoka stage, although correlation with patient survival was not reached. Such findings suggest involvement of these RTKs in thymic neoplasia, as well as their potential utility as treatment targets.

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Prognostic Significance of Metabolic Parameters by 18F-FDG PET/CT in Thymic Epithelial Tumors

Cancers ◽

10.3390/cancers13040712 ◽

2021 ◽

Vol 13 (4) ◽

pp. 712

Author(s):

Joohee Lee ◽

Young Seok Cho ◽

Jhingook Kim ◽

Young Mog Shim ◽

Kyung-Han Lee ◽

...

Keyword(s):

Multivariate Analysis ◽

Prognostic Factors ◽

Fdg Pet ◽

Univariate Analysis ◽

Thymic Epithelial Tumors ◽

Epithelial Tumors ◽

Masaoka Stage ◽

Pet Ct ◽

18F Fdg ◽

Fdg Pet Ct

Background: Imaging tumor FDG avidity could complement prognostic implication in thymic epithelial tumors. We thus investigated the prognostic value of volume-based 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT parameters in thymic epithelial tumors with other clinical prognostic factors. Methods: This is a retrospective study that included 83 patients who were diagnosed with thymic epithelial tumors and underwent pretreatment 18F-FDG PET/CT. PET parameters, including maximum and average standardized uptake values (SUVmax, SUVavg), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), were measured with a threshold of SUV 2.5. Univariate and multivariate analysis of PET parameters and clinicopathologic variables for time-to-progression was performed by using a Cox proportional hazard regression model. Results: There were 21 low-risk thymomas (25.3%), 27 high-risk thymomas (32.5%), and 35 thymic carcinomas (42.2%). Recurrence or disease progression occurred in 24 patients (28.9%). On univariate analysis, Masaoka stage (p < 0.001); histologic types (p = 0.009); treatment modality (p = 0.001); and SUVmax, SUVavg, MTV, and TLG (all p < 0.001) were significant prognostic factors. SUVavg (p < 0.001) and Masaoka stage (p = 0.001) were independent prognostic factors on multivariate analysis. Conclusion: SUVavg and Masaoka stage are independent prognostic factors in thymic epithelial tumors.

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Fluorodeoxyglucose Positron Emission Tomography Can Provide Useful Information for Differentiating Thymic Epithelial Tumors

The Thoracic and Cardiovascular Surgeon ◽

10.1055/s-0037-1604208 ◽

2017 ◽

Vol 66 (04) ◽

pp. 345-349 ◽

Cited By ~ 3

Author(s):

Takanori Ayabe ◽

Kazuyo Tsuchiya ◽

Kunihide Nakamura ◽

Masaki Tomita

Keyword(s):

Positron Emission Tomography ◽

High Risk ◽

Low Risk ◽

Emission Tomography ◽

Histologic Type ◽

Thymic Epithelial Tumors ◽

Epithelial Tumors ◽

Masaoka Stage ◽

Positron Emission ◽

Stage Disease

Background We examined the usefulness of fluorodeoxyglucose (FDG) positron emission tomography (PET) in predicting the World Health Organization (WHO) histologic type and Masaoka stage of thymic epithelial tumors. Methods A total of 73 patients with thymic epithelial tumors who underwent preoperative FDG-PET were included. Relationships between the maximum standardized uptake value (SUVmax) and WHO histologic type and the Masaoka stage of the tumor were examined. Differences in SUVmax between the various groups were calculated. To avoid the effect of the tumor size on SUVmax, the ratio of SUVmax to tumor size (SUVmax/T) was also examined. Results There was a significant relationship between SUVmax and WHO histologic type. SUVmax of high-risk thymomas (types B2 and B3) was significantly higher than that of low-risk thymomas (types A, AB, and B1). SUVmax of thymic carcinomas was also significantly higher than those of the low-risk and high-risk groups. The relationship between the SUVmax/T and WHO histologic type showed more significant results. SUVmax and SUVmax/T showed higher values in patients with advanced Masaoka stage disease than in those with early-stage disease. Conclusions FDG-PET can provide useful information for differentiating thymic epithelial tumors. The SUVmax/T is more useful than the SUVmax for differentiating between low-risk and high-risk thymomas.

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A Prospective, Phase II Trial of Induction Chemotherapy with Docetaxel/Cisplatin for Masaoka Stage III/IV Thymic Epithelial Tumors

Annals of Oncology ◽

10.1016/s0923-7534(20)32491-1 ◽

2012 ◽

Vol 23 ◽

pp. xi157

Author(s):

S. Park ◽

K. Park ◽

M. Ahn ◽

J.S. Ahn ◽

J.-M. Sun ◽

...

Keyword(s):

Induction Chemotherapy ◽

Phase Ii ◽

Phase Ii Trial ◽

Stage Iii ◽

Thymic Epithelial Tumors ◽

Epithelial Tumors ◽

Masaoka Stage ◽

Prospective Phase

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Sphingomonas and Phenylobacterium As Major Microbiota in Thymic Epithelial Tumors

10.21203/rs.3.rs-666392/v1 ◽

2021 ◽

Author(s):

Rumi Higuchi ◽

Taichiro Goto ◽

Yosuke Hirotsu ◽

Sotaro Otake ◽

Toshio Oyama ◽

...

Keyword(s):

Polymerase Chain Reaction Amplification ◽

Alpha Diversity ◽

Type A ◽

Rrna Gene ◽

Type B ◽

Thymic Epithelial Tumors ◽

Linear Discriminant ◽

Epithelial Tumors ◽

Significant Difference ◽

Type A Thymoma

Abstract Background Microbiota has been reported to be closely associated with carcinogenesis and cancer progression. However, its involvement in the pathology of thymoma remains unknown. In this study, we aimed to identify thymoma-specific microbiota using resected thymoma samples. Methods Nineteen thymoma tissue samples were analyzed through polymerase-chain-reaction amplification and 16S rRNA gene sequencing. The subjects were grouped according to histology, driver mutation status in the GTF2I gene, PD-L1 status, and smoking habits. To identify the taxa composition of each sample, operational taxonomic units (OTUs) were classified on the effective tags with 97% identity. The Shannon index of the 97% identity OTUs was calculated to evaluate alpha diversity. The linear discriminant analysis effect size (LEfSe) method was used to compare the relative abundances of all bacterial taxa. Results We identified 107 OTUs in the tumor tissues, which were classified into 26 genera. Sphingomonas and Phenylobacterium were identified as abundant genera in almost all samples. No significant difference was determined in the alpha diversity within these groups; however, type A thymoma exhibited higher bacterial diversity than type B thymoma. Through LEfSe analysis, we identified the following differentially abundant taxa: Bacilli, Firmicutes, and Lactobacillales in type A thymoma; Proteobacteria in type B thymoma; Gammaproteobacteria in tumors harboring the GTF2I mutation; and Alphaproteobacteria in tumors without the GTF2I mutation. Conclusions Sphingomonas and Phenylobacterium were identified as dominant genera in thymic epithelial tumors. These genera appear to comprise thymoma-specific microbiota involved in tumor progression; thus, they could serve as targets for the prevention of thymoma.

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A Prospective Phase II Trial of Induction Chemotherapy with Docetaxel/Cisplatin for Masaoka Stage III/IV thymic Epithelial Tumors

Journal of Thoracic Oncology ◽

10.1097/jto.0b013e318292c41e ◽

2013 ◽

Vol 8 (7) ◽

pp. 959-966 ◽

Cited By ~ 19

Author(s):

Silvia Park ◽

Myung-ju Ahn ◽

Jin Seok Ahn ◽

Jong-Mu Sun ◽

Young Mog Shim ◽

...

Keyword(s):

Induction Chemotherapy ◽

Phase Ii ◽

Phase Ii Trial ◽

Stage Iii ◽

Thymic Epithelial Tumors ◽

Epithelial Tumors ◽

Masaoka Stage ◽

Prospective Phase

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Prognostic Implication of Immunohistochemical Runx2 Expression in Osteosarcoma

Tumori Journal ◽

10.1177/030089160909500307 ◽

2009 ◽

Vol 95 (3) ◽

pp. 311-316 ◽

Cited By ~ 44

Author(s):

Kyu Yeoun Won ◽

Hye-Rim Park ◽

Yong-Koo Park

Keyword(s):

Immunohistochemical Staining ◽

Prognostic Value ◽

Tissue Microarrays ◽

High Expression ◽

Clinicopathological Parameters ◽

Formalin Fixed Paraffin ◽

Formalin Fixed Paraffin Embedded ◽

Primary Bone ◽

The Relationship ◽

Clinicopathological Variables

Aims and background Osteosarcoma is the most common primary bone malignancy. Many genetic markers have proven prognostic value in osteosarcoma and studies are under way to determine their potential application as specific therapeutic targets. Runx2, Indian hedgehog (IHH), and Sox9 are proteins that play major roles in bone formation and tumorigenesis. We studied the protein expression of Runx2, IHH, and Sox9 in osteosarcoma and correlated their expression with clinicopathological variables. We also studied the prognostic value of the expression of these three genes in osteosarcoma. Methods and study design We produced 48 formalin-fixed, paraffin-embedded tissue microarrays containing osteosarcoma tissue cores for immunohistochemical staining of Runx2, IHH and Sox9. We evaluated the expression of each gene by immunohistochemical staining and analyzed the relationship between expression and clinicopathological parameters. Results High expression of Runx2 was significantly related to metastasis (P = 0.015). High expression of Runx2 indicated a trend toward a poor survival rate (P = 0.056). High expression of IHH and Sox9 were not related to any clinicopathological parameters. Conclusions High expression of Runx2 was significantly related to tumor metastasis in osteosarcoma. Our results suggest that overexpression of Runx2 might be a useful prognostic marker in osteosarcoma cases.

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Analysis of surgical treatment of Masaoka stage III-IV thymic epithelial tumors

General Thoracic and Cardiovascular Surgery ◽

10.1007/s11748-018-0996-9 ◽

2018 ◽

Vol 66 (12) ◽

pp. 731-735 ◽

Cited By ~ 2

Author(s):

Kazutoshi Hamanaka ◽

Tsutomu Koyama ◽

Shunichiro Matsuoka ◽

Tetsu Takeda ◽

Kentaro Miura ◽

...

Keyword(s):

Surgical Treatment ◽

Stage Iii ◽

Thymic Epithelial Tumors ◽

Epithelial Tumors ◽

Masaoka Stage

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Postoperative radiation for tumor control and overall survival in thymic epithelial tumors (TET): A matched-pair analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.8572 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 8572-8572

Author(s):

Feng Ming Kong ◽

Yong Zang ◽

Weili Wang ◽

Hong Zhang ◽

Jessica Smith ◽

...

Keyword(s):

Overall Survival ◽

Propensity Score ◽

Propensity Score Matching ◽

Cox Model ◽

Matched Pair ◽

Tumor Control ◽

Postoperative Radiation ◽

Single Institution ◽

Thymic Epithelial Tumors ◽

Epithelial Tumors

8572 Background: Due to lack of randomized trials, the role of postoperative radiation therapy (PORT) in thymic epithelial tumors (TET) remains controversial. This study aimed to evaluate whether PORT improves tumor control and overall survival (OS) in patients with resected TET in a large single institution database. Methods: This is a retrospective study of all TETs seen at Indiana University between 1975 and 2016. Patients with resected thymoma (T) or thymic carcinoma (TC) were eligible disregarding their margin status or stage. Study endpoints were progression free survival (PFS) and OS. Age, gender, race, tumor size, stage, pathology, grade, completeness of resection and adjuvant treatment modality were analyzed for significance on PFS and OS. Multivariate Cox model was used to identify significant factors for propensity score matching. Differences between the PORT and surgery alone group were estimated using stratified log-rank test. Results: A total of 478 patients with previous surgical resection were eligible. Masaoka Stage was: I-86 (22%); II-87 (23%); III-107 (28%); and IV-106 (27%), respectively. Multivariate analysis demonstrated that gender (HR = 1.4, p = 0.03), stage (HR = 1.3, p = 3×10-3), TC (HR = 1.6, p = 0.03) and PORT (HR = 1.6, p = 0.002) were significantly associated with PFS. Age (HR = 1.1, p = 4×10-7), TC (HR = 3.2, p = 3×10-5), stage (HR = 1.4, p = 0.003) were associated with OS. PORT was given to 126 (26%) patients. Propensity score matching based on independent prognostic factors identified 99 patients for PORT, matched to 285 patients without. The 5-/10-year intra-thoracic progression free rates were 77%/69% and 85%/68%, for patients with and without PORT (p = 0.009), respectively. The 5-/10-year PFS rates were 39%/18% and 61%/32%, for patients with and without PORT (p = 0.002), respectively. The median survival, 5-/10-year OS rates for patients treated with PORT were 150 (95%CI 111~277) months, 87%/57% and respectively, compared to 192 months (95%CI 167~279), 88%/69% for patients receiving surgery alone ( p = 0.13). Conclusions: This matched-paired analysis from a single institution suggests that PORT does not impact the PFS or OS in a selected population of resected TET.

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