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Objective: The diagnosis of thyroid tumors is based on histologic features, but the distinction between benign and malignant thyroid lesions is somehow difficult, especially in lesions with a follicular pattern. Thus, ancillary studies, such as immunohistochemistry (IHC), may be helpful. In this study, we aimed to evaluate the diagnostic value of 2 IHC markers, TROP-2 and HBME-1, in the diagnosis of thyroid cancers., Study Design: A total of 102 cases of thyroid lesions, including papillary thyroid carcinoma (classic variant) (29 cases), follicular variant of papillary thyroid carcinoma (21 cases), multinodular goiter (22 cases), follicular adenoma (24 cases), and follicular carcinoma (6 cases) were selected. The hematoxylin-eosin slides were reviewed for confirmation of diagnosis, and IHC examination for TROP-2 and HBME-1 was performed., Result: HBME-1 had 84% sensitivity and 98% specificity with a positive predictive value (PPV) of 98% and a negative predictive value (NPV) of 83%. TROP-2 had 93% sensitivity and 74% specificity with a PPV of 81% and an NPV of 90% in malignant thyroid lesions., Conclusion: IHC panel consisting of TROP-2 and HBME-1 can be used in equivocal follicular patterned lesions for the diagnosis of thyroid carcinomas.

Background: Papillary thyroid cancer (PTC) is the most common endocrine tumor with an increasing incidence. The dilemma in treating this cancer is how to discriminate the tumors with aggressive behavior from the indolent ones. Trophoblast cell surface antigen 2 (trop-2) has been identified in multiple epithelial cancers and proven to be associated with shortened overall survival and disease-free survival., Methods: In this study, we retrospectively collected the clinicopathologic characteristics of 145 patients who underwent surgery at Fudan University Shanghai Cancer Center (FUSCC), and a validation cohort from The Cancer Genome Atlas (TCGA) database was identified to support the conclusion. Quantitative real-time polymerase chain reaction (qPCR) was employed to determine trop-2 mRNA in cancer tissue and adjacent normal tissue of PTC. BRAFV600E mutation analysis was determined using Sanger sequencing. The correlation of trop-2 and clinical characteristics was analyzed with Mann-Whitney U, Kruskal-Wallis, χ 2 , and Fisher's exact tests., Results: Trop-2 overexpression was significantly associated with lymph node metastasis (LNM) (FUSCC, P<0.001; TCGA, P<0.001) and extrathyroidal extension(ETE) (FUSCC, P=0.006; TCGA, P<0.001) in both the FUSCC and TCGA cohorts. It also proved to be an independent risk factor for LNM and ETE in multivariate analysis in both cohorts. Furthermore, trop-2 expression was also associated with BRAFV600E mutation, P<0.001 in both cohorts., Conclusions: The study found that trop-2 overexpression was correlated with LNM and ETE. Additionally, it was associated with BRAF mutation, therefore, trop-2 overexpression was a potential biomarker for aggressive behaviors of PTC, also it could be an indication for targeted therapy., Competing Interests: None., (IJCEP Copyright © 2018.)

Abstract: Still little information is available on the efficacy and toxicity of anti-Trop-2 antibodies in man. Findings on antibodies anti-Trop-1/Ep-CAM, a paralog molecule of Trop-2, may provide preliminary indications, and a low-affinity anti-Trop-1/Ep-CAM monoclonal antibody, failed to show any benefit in colon cancer patients. Other anti-Trop-1 antibodies, e.g. MT201, may bear more promise, as may more advanced molecular forms, e.g. a BiTE design (MT110) or trifunctional antibodies (catumaxomab). However, the efficacy of these reagents in cancer patients still needs to be proven in randomized clinical trials. As for toxicity, the administration of ING-1, a high-affinity, human-engineered anti-Trop-1/Ep-CAM monoclonal antibody, caused cases of acute pancreatitis. The exocrine pancreas also expresses Trop-2. Hence, similar concerns should apply to the administration of anti-Trop-2 monoclonal antibodies to patients. More in general, contrary to the statements by Cubas et al., Trop-2/T-16/Mov-16 is expressed by several normal tissues in man, e.g. epidermis, exocervix, esophagus, tongue, urothelium, kidney, pancreas, trophoblast and breast. Hence, additional effort is required to develop Trop-2 into a useful immunotherapeutic target, by increasing anti-Trop-2 antibody efficacy, while keeping under control toxicity on expressing normal tissues. [Copyright &y& Elsevier]

In this study, we compared the diagnostic value of TROP-2 expression in distinguishing between benign and malignant thyroid lesions to those of HBME-1, CK19 and galectin-3. We selected 102 cases from our archive including 20 normal thyroid tissues, 23 follicular nodular diseases, 17 follicular adenomas, 20 follicular variant papillary carcinomas and 22 classical variant papillary carcinomas. Tissue microarrays constructed from these cases were immunohistochemically analyzed with HBME-1, CK19, galectin-3 and TROP-2. Respectively 73.8%, 83.3%, 69% and 50% of all papillary carcinomas were positive with HBME-1, CK19, galectin-3 and TROP-2. CK19 was positive respectively by 100%, 43.5% and 35.3% in cases of normal thyroid, follicular nodular diseases and follicular adenoma, while the other markers were negative. In distinguishing benign and malignant lesions, which constitutes this study, HBME-1, CK19, galectin-3 and TROP-2 were statistically significant (p < 0.001). In distinguishing cases of follicular variant papillary carcinoma from follicular nodular diseases and follicular adenoma, HBME-1 and galectin-3 were statistically significant (p < 0.001). Consequently, in this study, we found that all immunohistochemical markers were effective in distinguishing benign and malignant thyroid lesions. In determining malignancy, HBME-1 had the highest diagnostic accuracy, while CK19 was the most sensitive marker. The sensitivity increased when the markers were used together.

We aimed to evaluate the diagnostic utility of the novel immunohistochemical marker TROP-2 on thyroid specimens (226 tumours and 207 controls). Whole slide immunohistochemistry was performed and scored by automated digital image analysis. Non-neoplastic thyroid, follicular adenomas, follicular carcinomas, and medullary carcinomas were negative for TROP-2 immunostaining. The majority of papillary thyroid carcinoma (PTC) specimens (94/114, 82.5%) were positive for TROP-2; however, the pattern of staining differed significantly between the histopathological variants. All papillary microcarcinomas (mPTC), PTC classic variant (PTC cv), and tall cell variant (PTC tcv) were TROP-2 positive, with mainly diffuse staining. In contrast, less than half of the PTC follicular variant specimens were positive for TROP-2, with only focal immunoreactivity. TROP-2 could identify PTC cv with 98.1% sensitivity and 97.5% specificity. ROC curve analysis found that the presence of >10% of TROP-2 positive cells in a tumour supported a diagnosis of PTC. The study of intratumoural heterogeneity showed that low-volume cytological samples of PTC cv could be adequately assessed by TROP-2 immunostaining. The TROP-2 H-score (intensity multiplied by proportion) was significantly associated with PTC variant and capsular invasion in encapsulated PTC follicular variant (p<0.001). None of the baseline (age, gender) and clinical (tumour size, nodal disease, stage) parameters were correlated with TROP-2 expression. In conclusion, TROP-2 membranous staining is a very sensitive and specific marker for PTC cv, PTC tcv, and mPTC, with high overall specificity for PTC., (Copyright © 2016 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

TROP-2 is a type I transmembrane glycoprotein which is over-expressed in various malignancies, and is related to epithelial cell adhesion molecule (EpCAM), also called TROP-1, gp40, and KSA. In this study, we evaluated TROP-2 expression in papillary thyroid carcinoma (PTC) and compared it to other thyroid neoplastic and non-neoplastic lesions. Immunohistochemical (IHC) evaluation for TROP-2 was performed on 137 thyroid fine needle aspiration (FNA) cell blocks (CB) which included classic PTC (64), follicular variant PTC (FVPTC) (10), anaplastic thyroid carcinoma (AC) (2), medullary carcinoma (MC) (8), follicular neoplasms (FN) (8), Hurthle cell neoplasms (HCN) (9), follicular lesion of uncertain significance (FLUS) (12), and benign thyroid nodule (BTN) (24). IHC for TROP-2 expression was also performed on 331 BTN and malignant tumor tissue sections in tissue microarray (TMA). Membranous staining in >5% of tumor cells was considered positive. TROP-2 stained 61 of 64 PTC CB, 7 of 10 FVPTC CB, and 9 of 12 FLUS CB. All other cases were negative for TROP-2. TROP-2 showed a sensitivity of 95.31% and specificity of 89% for classic PTC in FNA CB. In TMA samples, TROP-2 stained 54 of 60 classic PTC cases and hence showed a high sensitivity and specificity. All BTN in CB and TMA were negative. We conclude that TROP-2 is a highly sensitive and specific IHC marker for identifying classic PTC. TROP-2 may play an important role in diagnosing classic PTC, especially in equivocal cases. This study also identifies a strong role for TROP-2 in separating PTC from BTN., (© 2015 Wiley Periodicals, Inc.)

Cancer stem cells (CSCs) play a key role in initiation and development of cancer and are attractive targets for therapy. The identification of CSC surface receptors to be used as therapeutic targets in vivo remains a difficult task. In this study, we assessed the expression pattern of three surface receptors: CD133, Trop-2 and alpha2beta1 integrin in human prostate cancer in order to identify CSC-niches. CD133 was found to be expressed in small clusters of cells localized in focal areas of benign as well as malignant lesions, suggesting that this protein is a bona fide marker of the prostate stem/progenitor compartment. Trop-2 was localized in both basal and luminal layers of benign glands and was highly expressed in malignant lesions. Moreover, isolated cells in benign and malignant areas were found to co-express both CD133 and Trop-2. alpha2beta1 integrin was expressed in the prostatic epithelium as well as in the surrounding stroma, limiting its utility as a marker of CSCs. In summary, we demonstrate that the combination of CD133 and Trop-2 is useful to mark putative CSC-containing compartments in human prostate.